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Research Report – Example, Writing Guide and Types

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Research Report

Definition:

Research Report is a written document that presents the results of a research project or study, including the research question, methodology, results, and conclusions, in a clear and objective manner.

The purpose of a research report is to communicate the findings of the research to the intended audience, which could be other researchers, stakeholders, or the general public.

Components of Research Report

Components of Research Report are as follows:

Introduction

The introduction sets the stage for the research report and provides a brief overview of the research question or problem being investigated. It should include a clear statement of the purpose of the study and its significance or relevance to the field of research. It may also provide background information or a literature review to help contextualize the research.

Literature Review

The literature review provides a critical analysis and synthesis of the existing research and scholarship relevant to the research question or problem. It should identify the gaps, inconsistencies, and contradictions in the literature and show how the current study addresses these issues. The literature review also establishes the theoretical framework or conceptual model that guides the research.

Methodology

The methodology section describes the research design, methods, and procedures used to collect and analyze data. It should include information on the sample or participants, data collection instruments, data collection procedures, and data analysis techniques. The methodology should be clear and detailed enough to allow other researchers to replicate the study.

The results section presents the findings of the study in a clear and objective manner. It should provide a detailed description of the data and statistics used to answer the research question or test the hypothesis. Tables, graphs, and figures may be included to help visualize the data and illustrate the key findings.

The discussion section interprets the results of the study and explains their significance or relevance to the research question or problem. It should also compare the current findings with those of previous studies and identify the implications for future research or practice. The discussion should be based on the results presented in the previous section and should avoid speculation or unfounded conclusions.

The conclusion summarizes the key findings of the study and restates the main argument or thesis presented in the introduction. It should also provide a brief overview of the contributions of the study to the field of research and the implications for practice or policy.

The references section lists all the sources cited in the research report, following a specific citation style, such as APA or MLA.

The appendices section includes any additional material, such as data tables, figures, or instruments used in the study, that could not be included in the main text due to space limitations.

Types of Research Report

Types of Research Report are as follows:

Thesis is a type of research report. A thesis is a long-form research document that presents the findings and conclusions of an original research study conducted by a student as part of a graduate or postgraduate program. It is typically written by a student pursuing a higher degree, such as a Master’s or Doctoral degree, although it can also be written by researchers or scholars in other fields.

Research Paper

Research paper is a type of research report. A research paper is a document that presents the results of a research study or investigation. Research papers can be written in a variety of fields, including science, social science, humanities, and business. They typically follow a standard format that includes an introduction, literature review, methodology, results, discussion, and conclusion sections.

Technical Report

A technical report is a detailed report that provides information about a specific technical or scientific problem or project. Technical reports are often used in engineering, science, and other technical fields to document research and development work.

Progress Report

A progress report provides an update on the progress of a research project or program over a specific period of time. Progress reports are typically used to communicate the status of a project to stakeholders, funders, or project managers.

Feasibility Report

A feasibility report assesses the feasibility of a proposed project or plan, providing an analysis of the potential risks, benefits, and costs associated with the project. Feasibility reports are often used in business, engineering, and other fields to determine the viability of a project before it is undertaken.

Field Report

A field report documents observations and findings from fieldwork, which is research conducted in the natural environment or setting. Field reports are often used in anthropology, ecology, and other social and natural sciences.

Experimental Report

An experimental report documents the results of a scientific experiment, including the hypothesis, methods, results, and conclusions. Experimental reports are often used in biology, chemistry, and other sciences to communicate the results of laboratory experiments.

Case Study Report

A case study report provides an in-depth analysis of a specific case or situation, often used in psychology, social work, and other fields to document and understand complex cases or phenomena.

Literature Review Report

A literature review report synthesizes and summarizes existing research on a specific topic, providing an overview of the current state of knowledge on the subject. Literature review reports are often used in social sciences, education, and other fields to identify gaps in the literature and guide future research.

Research Report Example

Following is a Research Report Example sample for Students:

Title: The Impact of Social Media on Academic Performance among High School Students

This study aims to investigate the relationship between social media use and academic performance among high school students. The study utilized a quantitative research design, which involved a survey questionnaire administered to a sample of 200 high school students. The findings indicate that there is a negative correlation between social media use and academic performance, suggesting that excessive social media use can lead to poor academic performance among high school students. The results of this study have important implications for educators, parents, and policymakers, as they highlight the need for strategies that can help students balance their social media use and academic responsibilities.

Introduction:

Social media has become an integral part of the lives of high school students. With the widespread use of social media platforms such as Facebook, Twitter, Instagram, and Snapchat, students can connect with friends, share photos and videos, and engage in discussions on a range of topics. While social media offers many benefits, concerns have been raised about its impact on academic performance. Many studies have found a negative correlation between social media use and academic performance among high school students (Kirschner & Karpinski, 2010; Paul, Baker, & Cochran, 2012).

Given the growing importance of social media in the lives of high school students, it is important to investigate its impact on academic performance. This study aims to address this gap by examining the relationship between social media use and academic performance among high school students.

Methodology:

The study utilized a quantitative research design, which involved a survey questionnaire administered to a sample of 200 high school students. The questionnaire was developed based on previous studies and was designed to measure the frequency and duration of social media use, as well as academic performance.

The participants were selected using a convenience sampling technique, and the survey questionnaire was distributed in the classroom during regular school hours. The data collected were analyzed using descriptive statistics and correlation analysis.

The findings indicate that the majority of high school students use social media platforms on a daily basis, with Facebook being the most popular platform. The results also show a negative correlation between social media use and academic performance, suggesting that excessive social media use can lead to poor academic performance among high school students.

Discussion:

The results of this study have important implications for educators, parents, and policymakers. The negative correlation between social media use and academic performance suggests that strategies should be put in place to help students balance their social media use and academic responsibilities. For example, educators could incorporate social media into their teaching strategies to engage students and enhance learning. Parents could limit their children’s social media use and encourage them to prioritize their academic responsibilities. Policymakers could develop guidelines and policies to regulate social media use among high school students.

Conclusion:

In conclusion, this study provides evidence of the negative impact of social media on academic performance among high school students. The findings highlight the need for strategies that can help students balance their social media use and academic responsibilities. Further research is needed to explore the specific mechanisms by which social media use affects academic performance and to develop effective strategies for addressing this issue.

Limitations:

One limitation of this study is the use of convenience sampling, which limits the generalizability of the findings to other populations. Future studies should use random sampling techniques to increase the representativeness of the sample. Another limitation is the use of self-reported measures, which may be subject to social desirability bias. Future studies could use objective measures of social media use and academic performance, such as tracking software and school records.

Implications:

The findings of this study have important implications for educators, parents, and policymakers. Educators could incorporate social media into their teaching strategies to engage students and enhance learning. For example, teachers could use social media platforms to share relevant educational resources and facilitate online discussions. Parents could limit their children’s social media use and encourage them to prioritize their academic responsibilities. They could also engage in open communication with their children to understand their social media use and its impact on their academic performance. Policymakers could develop guidelines and policies to regulate social media use among high school students. For example, schools could implement social media policies that restrict access during class time and encourage responsible use.

References:

• Kirschner, P. A., & Karpinski, A. C. (2010). Facebook® and academic performance. Computers in Human Behavior, 26(6), 1237-1245.
• Paul, J. A., Baker, H. M., & Cochran, J. D. (2012). Effect of online social networking on student academic performance. Journal of the Research Center for Educational Technology, 8(1), 1-19.
• Pantic, I. (2014). Online social networking and mental health. Cyberpsychology, Behavior, and Social Networking, 17(10), 652-657.
• Rosen, L. D., Carrier, L. M., & Cheever, N. A. (2013). Facebook and texting made me do it: Media-induced task-switching while studying. Computers in Human Behavior, 29(3), 948-958.

Note*: Above mention, Example is just a sample for the students’ guide. Do not directly copy and paste as your College or University assignment. Kindly do some research and Write your own.

Applications of Research Report

Research reports have many applications, including:

• Communicating research findings: The primary application of a research report is to communicate the results of a study to other researchers, stakeholders, or the general public. The report serves as a way to share new knowledge, insights, and discoveries with others in the field.
• Informing policy and practice : Research reports can inform policy and practice by providing evidence-based recommendations for decision-makers. For example, a research report on the effectiveness of a new drug could inform regulatory agencies in their decision-making process.
• Supporting further research: Research reports can provide a foundation for further research in a particular area. Other researchers may use the findings and methodology of a report to develop new research questions or to build on existing research.
• Evaluating programs and interventions : Research reports can be used to evaluate the effectiveness of programs and interventions in achieving their intended outcomes. For example, a research report on a new educational program could provide evidence of its impact on student performance.
• Demonstrating impact : Research reports can be used to demonstrate the impact of research funding or to evaluate the success of research projects. By presenting the findings and outcomes of a study, research reports can show the value of research to funders and stakeholders.
• Enhancing professional development : Research reports can be used to enhance professional development by providing a source of information and learning for researchers and practitioners in a particular field. For example, a research report on a new teaching methodology could provide insights and ideas for educators to incorporate into their own practice.

How to write Research Report

Here are some steps you can follow to write a research report:

• Identify the research question: The first step in writing a research report is to identify your research question. This will help you focus your research and organize your findings.
• Conduct research : Once you have identified your research question, you will need to conduct research to gather relevant data and information. This can involve conducting experiments, reviewing literature, or analyzing data.
• Organize your findings: Once you have gathered all of your data, you will need to organize your findings in a way that is clear and understandable. This can involve creating tables, graphs, or charts to illustrate your results.
• Write the report: Once you have organized your findings, you can begin writing the report. Start with an introduction that provides background information and explains the purpose of your research. Next, provide a detailed description of your research methods and findings. Finally, summarize your results and draw conclusions based on your findings.
• Proofread and edit: After you have written your report, be sure to proofread and edit it carefully. Check for grammar and spelling errors, and make sure that your report is well-organized and easy to read.
• Include a reference list: Be sure to include a list of references that you used in your research. This will give credit to your sources and allow readers to further explore the topic if they choose.
• Format your report: Finally, format your report according to the guidelines provided by your instructor or organization. This may include formatting requirements for headings, margins, fonts, and spacing.

Purpose of Research Report

The purpose of a research report is to communicate the results of a research study to a specific audience, such as peers in the same field, stakeholders, or the general public. The report provides a detailed description of the research methods, findings, and conclusions.

Some common purposes of a research report include:

• Sharing knowledge: A research report allows researchers to share their findings and knowledge with others in their field. This helps to advance the field and improve the understanding of a particular topic.
• Identifying trends: A research report can identify trends and patterns in data, which can help guide future research and inform decision-making.
• Addressing problems: A research report can provide insights into problems or issues and suggest solutions or recommendations for addressing them.
• Evaluating programs or interventions : A research report can evaluate the effectiveness of programs or interventions, which can inform decision-making about whether to continue, modify, or discontinue them.
• Meeting regulatory requirements: In some fields, research reports are required to meet regulatory requirements, such as in the case of drug trials or environmental impact studies.

When to Write Research Report

A research report should be written after completing the research study. This includes collecting data, analyzing the results, and drawing conclusions based on the findings. Once the research is complete, the report should be written in a timely manner while the information is still fresh in the researcher’s mind.

In academic settings, research reports are often required as part of coursework or as part of a thesis or dissertation. In this case, the report should be written according to the guidelines provided by the instructor or institution.

In other settings, such as in industry or government, research reports may be required to inform decision-making or to comply with regulatory requirements. In these cases, the report should be written as soon as possible after the research is completed in order to inform decision-making in a timely manner.

Overall, the timing of when to write a research report depends on the purpose of the research, the expectations of the audience, and any regulatory requirements that need to be met. However, it is important to complete the report in a timely manner while the information is still fresh in the researcher’s mind.

Characteristics of Research Report

There are several characteristics of a research report that distinguish it from other types of writing. These characteristics include:

• Objective: A research report should be written in an objective and unbiased manner. It should present the facts and findings of the research study without any personal opinions or biases.
• Systematic: A research report should be written in a systematic manner. It should follow a clear and logical structure, and the information should be presented in a way that is easy to understand and follow.
• Detailed: A research report should be detailed and comprehensive. It should provide a thorough description of the research methods, results, and conclusions.
• Accurate : A research report should be accurate and based on sound research methods. The findings and conclusions should be supported by data and evidence.
• Organized: A research report should be well-organized. It should include headings and subheadings to help the reader navigate the report and understand the main points.
• Clear and concise: A research report should be written in clear and concise language. The information should be presented in a way that is easy to understand, and unnecessary jargon should be avoided.
• Citations and references: A research report should include citations and references to support the findings and conclusions. This helps to give credit to other researchers and to provide readers with the opportunity to further explore the topic.

Advantages of Research Report

Research reports have several advantages, including:

• Communicating research findings: Research reports allow researchers to communicate their findings to a wider audience, including other researchers, stakeholders, and the general public. This helps to disseminate knowledge and advance the understanding of a particular topic.
• Providing evidence for decision-making : Research reports can provide evidence to inform decision-making, such as in the case of policy-making, program planning, or product development. The findings and conclusions can help guide decisions and improve outcomes.
• Supporting further research: Research reports can provide a foundation for further research on a particular topic. Other researchers can build on the findings and conclusions of the report, which can lead to further discoveries and advancements in the field.
• Demonstrating expertise: Research reports can demonstrate the expertise of the researchers and their ability to conduct rigorous and high-quality research. This can be important for securing funding, promotions, and other professional opportunities.
• Meeting regulatory requirements: In some fields, research reports are required to meet regulatory requirements, such as in the case of drug trials or environmental impact studies. Producing a high-quality research report can help ensure compliance with these requirements.

Limitations of Research Report

Despite their advantages, research reports also have some limitations, including:

• Time-consuming: Conducting research and writing a report can be a time-consuming process, particularly for large-scale studies. This can limit the frequency and speed of producing research reports.
• Expensive: Conducting research and producing a report can be expensive, particularly for studies that require specialized equipment, personnel, or data. This can limit the scope and feasibility of some research studies.
• Limited generalizability: Research studies often focus on a specific population or context, which can limit the generalizability of the findings to other populations or contexts.
• Potential bias : Researchers may have biases or conflicts of interest that can influence the findings and conclusions of the research study. Additionally, participants may also have biases or may not be representative of the larger population, which can limit the validity and reliability of the findings.
• Accessibility: Research reports may be written in technical or academic language, which can limit their accessibility to a wider audience. Additionally, some research may be behind paywalls or require specialized access, which can limit the ability of others to read and use the findings.

About the author

Muhammad Hassan

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Writing up a Research Report

• First Online: 04 January 2024

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• Michael Blankenagel 3  

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A research report is one big argument about how and why you came up with your conclusions. To make it a convincing argument, a typical guiding structure has developed. In the different chapters, there are distinct issues that need to be addressed to explain to the reader why your conclusions are valid. The governing principle for writing the report is full disclosure: to explain everything and ensure replicability by another researcher.

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Barros, L. O. (2016). The only academic phrasebook you’ll ever need . Createspace Independent Publishing Platform.

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Field, A. (2016). An adventure in statistics. The reality enigma . SAGE.

Field, A. (2020). Discovering statistics using IBM SPSS statistics (5th ed.). SAGE.

Früh, M., Keimer, I., & Blankenagel, M. (2019). The impact of Balanced Scorecard excellence on shareholder returns. IFZ Working Paper No. 0003/2019. https://zenodo.org/record/2571603#.YMDUafkzZaQ . Accessed: 9 June 2021.

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Yin, R. K. (2013). Case study research: Design and methods (5th ed.). SAGE.

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Hunziker, S., Blankenagel, M. (2024). Writing up a Research Report. In: Research Design in Business and Management. Springer Gabler, Wiesbaden. https://doi.org/10.1007/978-3-658-42739-9_4

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Uncomplicated Reviews of Educational Research Methods

• Writing a Research Report

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This review covers the basic elements of a research report. This is a general guide for what you will see in journal articles or dissertations. This format assumes a mixed methods study, but you can leave out either quantitative or qualitative sections if you only used a single methodology.

This review is divided into sections for easy reference. There are five MAJOR parts of a Research Report:

1.    Introduction 2.    Review of Literature 3.    Methods 4.    Results 5.    Discussion

As a general guide, the Introduction, Review of Literature, and Methods should be about 1/3 of your paper, Discussion 1/3, then Results 1/3.

Section 1 : Cover Sheet (APA format cover sheet) optional, if required.

Section 2: Abstract (a basic summary of the report, including sample, treatment, design, results, and implications) (≤ 150 words) optional, if required.

Section 3 : Introduction (1-3 paragraphs) •    Basic introduction •    Supportive statistics (can be from periodicals) •    Statement of Purpose •    Statement of Significance

Section 4 : Research question(s) or hypotheses •    An overall research question (optional) •    A quantitative-based (hypotheses) •    A qualitative-based (research questions) Note: You will generally have more than one, especially if using hypotheses.

Section 5: Review of Literature ▪    Should be organized by subheadings ▪    Should adequately support your study using supporting, related, and/or refuting evidence ▪    Is a synthesis, not a collection of individual summaries

Section 6: Methods ▪    Procedure: Describe data gathering or participant recruitment, including IRB approval ▪    Sample: Describe the sample or dataset, including basic demographics ▪    Setting: Describe the setting, if applicable (generally only in qualitative designs) ▪    Treatment: If applicable, describe, in detail, how you implemented the treatment ▪    Instrument: Describe, in detail, how you implemented the instrument; Describe the reliability and validity associated with the instrument ▪    Data Analysis: Describe type of procedure (t-test, interviews, etc.) and software (if used)

Section 7: Results ▪    Restate Research Question 1 (Quantitative) ▪    Describe results ▪    Restate Research Question 2 (Qualitative) ▪    Describe results

Section 8: Discussion ▪    Restate Overall Research Question ▪    Describe how the results, when taken together, answer the overall question ▪    ***Describe how the results confirm or contrast the literature you reviewed

Section 9: Recommendations (if applicable, generally related to practice)

Section 10: Limitations ▪    Discuss, in several sentences, the limitations of this study. ▪    Research Design (overall, then info about the limitations of each separately) ▪    Sample ▪    Instrument/s ▪    Other limitations

Section 11: Conclusion (A brief closing summary)

Section 12: References (APA format)

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Chapter 11: Presenting Your Research

Writing a Research Report in American Psychological Association (APA) Style

Learning Objectives

• Identify the major sections of an APA-style research report and the basic contents of each section.
• Plan and write an effective APA-style research report.

In this section, we look at how to write an APA-style empirical research report , an article that presents the results of one or more new studies. Recall that the standard sections of an empirical research report provide a kind of outline. Here we consider each of these sections in detail, including what information it contains, how that information is formatted and organized, and tips for writing each section. At the end of this section is a sample APA-style research report that illustrates many of these principles.

Sections of a Research Report

Title page and abstract.

An APA-style research report begins with a  title page . The title is centred in the upper half of the page, with each important word capitalized. The title should clearly and concisely (in about 12 words or fewer) communicate the primary variables and research questions. This sometimes requires a main title followed by a subtitle that elaborates on the main title, in which case the main title and subtitle are separated by a colon. Here are some titles from recent issues of professional journals published by the American Psychological Association.

• Sex Differences in Coping Styles and Implications for Depressed Mood
• Effects of Aging and Divided Attention on Memory for Items and Their Contexts
• Computer-Assisted Cognitive Behavioural Therapy for Child Anxiety: Results of a Randomized Clinical Trial
• Virtual Driving and Risk Taking: Do Racing Games Increase Risk-Taking Cognitions, Affect, and Behaviour?

Below the title are the authors’ names and, on the next line, their institutional affiliation—the university or other institution where the authors worked when they conducted the research. As we have already seen, the authors are listed in an order that reflects their contribution to the research. When multiple authors have made equal contributions to the research, they often list their names alphabetically or in a randomly determined order.

In some areas of psychology, the titles of many empirical research reports are informal in a way that is perhaps best described as “cute.” They usually take the form of a play on words or a well-known expression that relates to the topic under study. Here are some examples from recent issues of the Journal Psychological Science .

• “Smells Like Clean Spirit: Nonconscious Effects of Scent on Cognition and Behavior”
• “Time Crawls: The Temporal Resolution of Infants’ Visual Attention”
• “Scent of a Woman: Men’s Testosterone Responses to Olfactory Ovulation Cues”
• “Apocalypse Soon?: Dire Messages Reduce Belief in Global Warming by Contradicting Just-World Beliefs”
• “Serial vs. Parallel Processing: Sometimes They Look Like Tweedledum and Tweedledee but They Can (and Should) Be Distinguished”
• “How Do I Love Thee? Let Me Count the Words: The Social Effects of Expressive Writing”

Individual researchers differ quite a bit in their preference for such titles. Some use them regularly, while others never use them. What might be some of the pros and cons of using cute article titles?

For articles that are being submitted for publication, the title page also includes an author note that lists the authors’ full institutional affiliations, any acknowledgments the authors wish to make to agencies that funded the research or to colleagues who commented on it, and contact information for the authors. For student papers that are not being submitted for publication—including theses—author notes are generally not necessary.

The  abstract  is a summary of the study. It is the second page of the manuscript and is headed with the word  Abstract . The first line is not indented. The abstract presents the research question, a summary of the method, the basic results, and the most important conclusions. Because the abstract is usually limited to about 200 words, it can be a challenge to write a good one.

Introduction

The  introduction  begins on the third page of the manuscript. The heading at the top of this page is the full title of the manuscript, with each important word capitalized as on the title page. The introduction includes three distinct subsections, although these are typically not identified by separate headings. The opening introduces the research question and explains why it is interesting, the literature review discusses relevant previous research, and the closing restates the research question and comments on the method used to answer it.

The Opening

The  opening , which is usually a paragraph or two in length, introduces the research question and explains why it is interesting. To capture the reader’s attention, researcher Daryl Bem recommends starting with general observations about the topic under study, expressed in ordinary language (not technical jargon)—observations that are about people and their behaviour (not about researchers or their research; Bem, 2003 [1] ). Concrete examples are often very useful here. According to Bem, this would be a poor way to begin a research report:

Festinger’s theory of cognitive dissonance received a great deal of attention during the latter part of the 20th century (p. 191)

The following would be much better:

The individual who holds two beliefs that are inconsistent with one another may feel uncomfortable. For example, the person who knows that he or she enjoys smoking but believes it to be unhealthy may experience discomfort arising from the inconsistency or disharmony between these two thoughts or cognitions. This feeling of discomfort was called cognitive dissonance by social psychologist Leon Festinger (1957), who suggested that individuals will be motivated to remove this dissonance in whatever way they can (p. 191).

After capturing the reader’s attention, the opening should go on to introduce the research question and explain why it is interesting. Will the answer fill a gap in the literature? Will it provide a test of an important theory? Does it have practical implications? Giving readers a clear sense of what the research is about and why they should care about it will motivate them to continue reading the literature review—and will help them make sense of it.

Breaking the Rules

Researcher Larry Jacoby reported several studies showing that a word that people see or hear repeatedly can seem more familiar even when they do not recall the repetitions—and that this tendency is especially pronounced among older adults. He opened his article with the following humourous anecdote:

A friend whose mother is suffering symptoms of Alzheimer’s disease (AD) tells the story of taking her mother to visit a nursing home, preliminary to her mother’s moving there. During an orientation meeting at the nursing home, the rules and regulations were explained, one of which regarded the dining room. The dining room was described as similar to a fine restaurant except that tipping was not required. The absence of tipping was a central theme in the orientation lecture, mentioned frequently to emphasize the quality of care along with the advantages of having paid in advance. At the end of the meeting, the friend’s mother was asked whether she had any questions. She replied that she only had one question: “Should I tip?” (Jacoby, 1999, p. 3)

Although both humour and personal anecdotes are generally discouraged in APA-style writing, this example is a highly effective way to start because it both engages the reader and provides an excellent real-world example of the topic under study.

The Literature Review

Immediately after the opening comes the  literature review , which describes relevant previous research on the topic and can be anywhere from several paragraphs to several pages in length. However, the literature review is not simply a list of past studies. Instead, it constitutes a kind of argument for why the research question is worth addressing. By the end of the literature review, readers should be convinced that the research question makes sense and that the present study is a logical next step in the ongoing research process.

Like any effective argument, the literature review must have some kind of structure. For example, it might begin by describing a phenomenon in a general way along with several studies that demonstrate it, then describing two or more competing theories of the phenomenon, and finally presenting a hypothesis to test one or more of the theories. Or it might describe one phenomenon, then describe another phenomenon that seems inconsistent with the first one, then propose a theory that resolves the inconsistency, and finally present a hypothesis to test that theory. In applied research, it might describe a phenomenon or theory, then describe how that phenomenon or theory applies to some important real-world situation, and finally suggest a way to test whether it does, in fact, apply to that situation.

Looking at the literature review in this way emphasizes a few things. First, it is extremely important to start with an outline of the main points that you want to make, organized in the order that you want to make them. The basic structure of your argument, then, should be apparent from the outline itself. Second, it is important to emphasize the structure of your argument in your writing. One way to do this is to begin the literature review by summarizing your argument even before you begin to make it. “In this article, I will describe two apparently contradictory phenomena, present a new theory that has the potential to resolve the apparent contradiction, and finally present a novel hypothesis to test the theory.” Another way is to open each paragraph with a sentence that summarizes the main point of the paragraph and links it to the preceding points. These opening sentences provide the “transitions” that many beginning researchers have difficulty with. Instead of beginning a paragraph by launching into a description of a previous study, such as “Williams (2004) found that…,” it is better to start by indicating something about why you are describing this particular study. Here are some simple examples:

Another example of this phenomenon comes from the work of Williams (2004).

Williams (2004) offers one explanation of this phenomenon.

An alternative perspective has been provided by Williams (2004).

We used a method based on the one used by Williams (2004).

Finally, remember that your goal is to construct an argument for why your research question is interesting and worth addressing—not necessarily why your favourite answer to it is correct. In other words, your literature review must be balanced. If you want to emphasize the generality of a phenomenon, then of course you should discuss various studies that have demonstrated it. However, if there are other studies that have failed to demonstrate it, you should discuss them too. Or if you are proposing a new theory, then of course you should discuss findings that are consistent with that theory. However, if there are other findings that are inconsistent with it, again, you should discuss them too. It is acceptable to argue that the  balance  of the research supports the existence of a phenomenon or is consistent with a theory (and that is usually the best that researchers in psychology can hope for), but it is not acceptable to  ignore contradictory evidence. Besides, a large part of what makes a research question interesting is uncertainty about its answer.

The Closing

The  closing  of the introduction—typically the final paragraph or two—usually includes two important elements. The first is a clear statement of the main research question or hypothesis. This statement tends to be more formal and precise than in the opening and is often expressed in terms of operational definitions of the key variables. The second is a brief overview of the method and some comment on its appropriateness. Here, for example, is how Darley and Latané (1968) [2] concluded the introduction to their classic article on the bystander effect:

These considerations lead to the hypothesis that the more bystanders to an emergency, the less likely, or the more slowly, any one bystander will intervene to provide aid. To test this proposition it would be necessary to create a situation in which a realistic “emergency” could plausibly occur. Each subject should also be blocked from communicating with others to prevent his getting information about their behaviour during the emergency. Finally, the experimental situation should allow for the assessment of the speed and frequency of the subjects’ reaction to the emergency. The experiment reported below attempted to fulfill these conditions. (p. 378)

Thus the introduction leads smoothly into the next major section of the article—the method section.

The  method section  is where you describe how you conducted your study. An important principle for writing a method section is that it should be clear and detailed enough that other researchers could replicate the study by following your “recipe.” This means that it must describe all the important elements of the study—basic demographic characteristics of the participants, how they were recruited, whether they were randomly assigned, how the variables were manipulated or measured, how counterbalancing was accomplished, and so on. At the same time, it should avoid irrelevant details such as the fact that the study was conducted in Classroom 37B of the Industrial Technology Building or that the questionnaire was double-sided and completed using pencils.

The method section begins immediately after the introduction ends with the heading “Method” (not “Methods”) centred on the page. Immediately after this is the subheading “Participants,” left justified and in italics. The participants subsection indicates how many participants there were, the number of women and men, some indication of their age, other demographics that may be relevant to the study, and how they were recruited, including any incentives given for participation.

After the participants section, the structure can vary a bit. Figure 11.1 shows three common approaches. In the first, the participants section is followed by a design and procedure subsection, which describes the rest of the method. This works well for methods that are relatively simple and can be described adequately in a few paragraphs. In the second approach, the participants section is followed by separate design and procedure subsections. This works well when both the design and the procedure are relatively complicated and each requires multiple paragraphs.

What is the difference between design and procedure? The design of a study is its overall structure. What were the independent and dependent variables? Was the independent variable manipulated, and if so, was it manipulated between or within subjects? How were the variables operationally defined? The procedure is how the study was carried out. It often works well to describe the procedure in terms of what the participants did rather than what the researchers did. For example, the participants gave their informed consent, read a set of instructions, completed a block of four practice trials, completed a block of 20 test trials, completed two questionnaires, and were debriefed and excused.

In the third basic way to organize a method section, the participants subsection is followed by a materials subsection before the design and procedure subsections. This works well when there are complicated materials to describe. This might mean multiple questionnaires, written vignettes that participants read and respond to, perceptual stimuli, and so on. The heading of this subsection can be modified to reflect its content. Instead of “Materials,” it can be “Questionnaires,” “Stimuli,” and so on.

The  results section  is where you present the main results of the study, including the results of the statistical analyses. Although it does not include the raw data—individual participants’ responses or scores—researchers should save their raw data and make them available to other researchers who request them. Several journals now encourage the open sharing of raw data online.

Although there are no standard subsections, it is still important for the results section to be logically organized. Typically it begins with certain preliminary issues. One is whether any participants or responses were excluded from the analyses and why. The rationale for excluding data should be described clearly so that other researchers can decide whether it is appropriate. A second preliminary issue is how multiple responses were combined to produce the primary variables in the analyses. For example, if participants rated the attractiveness of 20 stimulus people, you might have to explain that you began by computing the mean attractiveness rating for each participant. Or if they recalled as many items as they could from study list of 20 words, did you count the number correctly recalled, compute the percentage correctly recalled, or perhaps compute the number correct minus the number incorrect? A third preliminary issue is the reliability of the measures. This is where you would present test-retest correlations, Cronbach’s α, or other statistics to show that the measures are consistent across time and across items. A final preliminary issue is whether the manipulation was successful. This is where you would report the results of any manipulation checks.

The results section should then tackle the primary research questions, one at a time. Again, there should be a clear organization. One approach would be to answer the most general questions and then proceed to answer more specific ones. Another would be to answer the main question first and then to answer secondary ones. Regardless, Bem (2003) [3] suggests the following basic structure for discussing each new result:

• Remind the reader of the research question.
• Give the answer to the research question in words.
• Present the relevant statistics.
• Qualify the answer if necessary.
• Summarize the result.

Notice that only Step 3 necessarily involves numbers. The rest of the steps involve presenting the research question and the answer to it in words. In fact, the basic results should be clear even to a reader who skips over the numbers.

The  discussion  is the last major section of the research report. Discussions usually consist of some combination of the following elements:

• Summary of the research
• Theoretical implications
• Practical implications
• Limitations
• Suggestions for future research

The discussion typically begins with a summary of the study that provides a clear answer to the research question. In a short report with a single study, this might require no more than a sentence. In a longer report with multiple studies, it might require a paragraph or even two. The summary is often followed by a discussion of the theoretical implications of the research. Do the results provide support for any existing theories? If not, how  can  they be explained? Although you do not have to provide a definitive explanation or detailed theory for your results, you at least need to outline one or more possible explanations. In applied research—and often in basic research—there is also some discussion of the practical implications of the research. How can the results be used, and by whom, to accomplish some real-world goal?

The theoretical and practical implications are often followed by a discussion of the study’s limitations. Perhaps there are problems with its internal or external validity. Perhaps the manipulation was not very effective or the measures not very reliable. Perhaps there is some evidence that participants did not fully understand their task or that they were suspicious of the intent of the researchers. Now is the time to discuss these issues and how they might have affected the results. But do not overdo it. All studies have limitations, and most readers will understand that a different sample or different measures might have produced different results. Unless there is good reason to think they  would have, however, there is no reason to mention these routine issues. Instead, pick two or three limitations that seem like they could have influenced the results, explain how they could have influenced the results, and suggest ways to deal with them.

Most discussions end with some suggestions for future research. If the study did not satisfactorily answer the original research question, what will it take to do so? What  new  research questions has the study raised? This part of the discussion, however, is not just a list of new questions. It is a discussion of two or three of the most important unresolved issues. This means identifying and clarifying each question, suggesting some alternative answers, and even suggesting ways they could be studied.

Finally, some researchers are quite good at ending their articles with a sweeping or thought-provoking conclusion. Darley and Latané (1968) [4] , for example, ended their article on the bystander effect by discussing the idea that whether people help others may depend more on the situation than on their personalities. Their final sentence is, “If people understand the situational forces that can make them hesitate to intervene, they may better overcome them” (p. 383). However, this kind of ending can be difficult to pull off. It can sound overreaching or just banal and end up detracting from the overall impact of the article. It is often better simply to end when you have made your final point (although you should avoid ending on a limitation).

The references section begins on a new page with the heading “References” centred at the top of the page. All references cited in the text are then listed in the format presented earlier. They are listed alphabetically by the last name of the first author. If two sources have the same first author, they are listed alphabetically by the last name of the second author. If all the authors are the same, then they are listed chronologically by the year of publication. Everything in the reference list is double-spaced both within and between references.

Appendices, Tables, and Figures

Appendices, tables, and figures come after the references. An  appendix  is appropriate for supplemental material that would interrupt the flow of the research report if it were presented within any of the major sections. An appendix could be used to present lists of stimulus words, questionnaire items, detailed descriptions of special equipment or unusual statistical analyses, or references to the studies that are included in a meta-analysis. Each appendix begins on a new page. If there is only one, the heading is “Appendix,” centred at the top of the page. If there is more than one, the headings are “Appendix A,” “Appendix B,” and so on, and they appear in the order they were first mentioned in the text of the report.

After any appendices come tables and then figures. Tables and figures are both used to present results. Figures can also be used to illustrate theories (e.g., in the form of a flowchart), display stimuli, outline procedures, and present many other kinds of information. Each table and figure appears on its own page. Tables are numbered in the order that they are first mentioned in the text (“Table 1,” “Table 2,” and so on). Figures are numbered the same way (“Figure 1,” “Figure 2,” and so on). A brief explanatory title, with the important words capitalized, appears above each table. Each figure is given a brief explanatory caption, where (aside from proper nouns or names) only the first word of each sentence is capitalized. More details on preparing APA-style tables and figures are presented later in the book.

Sample APA-Style Research Report

Figures 11.2, 11.3, 11.4, and 11.5 show some sample pages from an APA-style empirical research report originally written by undergraduate student Tomoe Suyama at California State University, Fresno. The main purpose of these figures is to illustrate the basic organization and formatting of an APA-style empirical research report, although many high-level and low-level style conventions can be seen here too.

Key Takeaways

• An APA-style empirical research report consists of several standard sections. The main ones are the abstract, introduction, method, results, discussion, and references.
• The introduction consists of an opening that presents the research question, a literature review that describes previous research on the topic, and a closing that restates the research question and comments on the method. The literature review constitutes an argument for why the current study is worth doing.
• The method section describes the method in enough detail that another researcher could replicate the study. At a minimum, it consists of a participants subsection and a design and procedure subsection.
• The results section describes the results in an organized fashion. Each primary result is presented in terms of statistical results but also explained in words.
• The discussion typically summarizes the study, discusses theoretical and practical implications and limitations of the study, and offers suggestions for further research.
• Practice: Look through an issue of a general interest professional journal (e.g.,  Psychological Science ). Read the opening of the first five articles and rate the effectiveness of each one from 1 ( very ineffective ) to 5 ( very effective ). Write a sentence or two explaining each rating.
• Practice: Find a recent article in a professional journal and identify where the opening, literature review, and closing of the introduction begin and end.
• Practice: Find a recent article in a professional journal and highlight in a different colour each of the following elements in the discussion: summary, theoretical implications, practical implications, limitations, and suggestions for future research.

Long Descriptions

Figure 11.1 long description: Table showing three ways of organizing an APA-style method section.

In the simple method, there are two subheadings: “Participants” (which might begin “The participants were…”) and “Design and procedure” (which might begin “There were three conditions…”).

In the typical method, there are three subheadings: “Participants” (“The participants were…”), “Design” (“There were three conditions…”), and “Procedure” (“Participants viewed each stimulus on the computer screen…”).

In the complex method, there are four subheadings: “Participants” (“The participants were…”), “Materials” (“The stimuli were…”), “Design” (“There were three conditions…”), and “Procedure” (“Participants viewed each stimulus on the computer screen…”). [Return to Figure 11.1]

• Bem, D. J. (2003). Writing the empirical journal article. In J. M. Darley, M. P. Zanna, & H. R. Roediger III (Eds.),  The compleat academic: A practical guide for the beginning social scientist  (2nd ed.). Washington, DC: American Psychological Association. ↵
• Darley, J. M., & Latané, B. (1968). Bystander intervention in emergencies: Diffusion of responsibility.  Journal of Personality and Social Psychology, 4 , 377–383. ↵

A type of research article which describes one or more new empirical studies conducted by the authors.

The page at the beginning of an APA-style research report containing the title of the article, the authors’ names, and their institutional affiliation.

A summary of a research study.

The third page of a manuscript containing the research question, the literature review, and comments about how to answer the research question.

An introduction to the research question and explanation for why this question is interesting.

A description of relevant previous research on the topic being discusses and an argument for why the research is worth addressing.

The end of the introduction, where the research question is reiterated and the method is commented upon.

The section of a research report where the method used to conduct the study is described.

The main results of the study, including the results from statistical analyses, are presented in a research article.

Section of a research report that summarizes the study's results and interprets them by referring back to the study's theoretical background.

Part of a research report which contains supplemental material.

Research Methods in Psychology - 2nd Canadian Edition Copyright © 2015 by Paul C. Price, Rajiv Jhangiani, & I-Chant A. Chiang is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License , except where otherwise noted.

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How to Write a Research Paper

If you already have a headache trying to understand what research paper is all about, we have created an ultimate guide for you on how to write a research paper. You will find all the answers to your questions regarding structure, planning, doing investigation, finding the topic that appeals to you. Plus, you will find out the secret to an excellent paper. Are you at the edge of your seat? Let us start with the basics then.

• What is a Research Paper
• Reasons for Writing a Research Paper
• Report Papers and Thesis Papers
• How to Start a Research Paper
• How to Choose a Topic for a Research Paper
• How to Write a Proposal for a Research Paper
• How to Write a Research Plan
• How to Do Research
• How to Write an Outline for a Research Paper
• How to Write a Thesis Statement for a Research Paper
• How to Write a Research Paper Rough Draft
• How to Write an Introduction for a Research Paper
• How to Write a Body of a Research Paper
• How to Write a Conclusion for a Research Paper
• How to Write an Abstract for a Research Paper
• How to Revise and Edit a Research Paper
• How to Write a Bibliography for a Research Paper
• What Makes a Good Research Paper

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What is a research paper.

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You probably know the saying ‘the devil is not as black as he is painted’. This particular saying is absolutely true when it comes to writing a research paper. Your feet are cold even with the thought of this assignment. You have heard terrifying stories from older students. You have never done this before, so certainly you are scared. What is a research paper? How should I start? What are all these requirements about?

Luckily, you have a friend in need. That is our writing service. First and foremost, let us clarify the definition. A research paper is a piece of academic writing that provides information about a particular topic that you’ve researched . In other words, you choose a topic: about historical events, the work of some artist, some social issues etc. Then you collect data on the given topic and analyze it. Finally, you put your analysis on paper. See, it is not as scary as it seems. If you are still having doubts, whether you can handle it yourself, we are here to help you. Our team of writers can help you choose the topic, or give you advice on how to plan your work, or how to start, or craft a paper for you. Just contact us 24/7 and see everything yourself.

5 Reasons for Writing a Research Paper

Why should I spend my time writing some academic paper? What is the use of it? Is not some practical knowledge more important? The list of questions is endless when it comes to a research paper. That is why we have outlined 5 main reasons why writing a research paper is a good thing.

• You will learn how to organize your time

If you want to write a research paper, you will have to learn how to manage your time. This type of assignment cannot be done overnight. It requires careful planning and you will need to learn how to do it. Later, you will be able to use these time-managing skills in your personal life, so why not developing them?

• You will discover your writing skills

You cannot know something before you try it. This rule relates to writing as well. You cannot claim that you cannot write until you try it yourself. It will be really difficult at the beginning, but then the words will come to your head themselves.

• You will improve your analytical skills

Writing a research paper is all about investigation and analysis. You will need to collect data, examine and classify it. These skills are needed in modern life more than anything else is.

• You will gain confidence

Once you do your own research, it gives you the feeling of confidence in yourself. The reason is simple human brain likes solving puzzles and your assignment is just another puzzle to be solved.

• You will learn how to persuade the reader

When you write your paper, you should always remember that you are writing it for someone to read. Moreover, you want this someone to believe in your ideas. For this reason, you will have to learn different convincing methods and techniques. You will learn how to make your writing persuasive. In turns, you will be able to use these methods in real life.

What is the Difference between Report and Thesis Papers?

A common question is ‘what is the difference between a report paper and a thesis paper?’ The difference lies in the aim of these two assignments. While the former aims at presenting the information, the latter aims at providing your opinion on the matter. In other words, in a report paper you have to summarize your findings. In a thesis paper, you choose some issue and defend your point of view by persuading the reader. It is that simple.

A thesis paper is a more common assignment than a report paper. This task will help a professor to evaluate your analytical skills and skills to present your ideas logically. These skills are more important than just the ability to collect and summarize data.

How to Write a Research Paper Step by Step

Research comes from the French word  rechercher , meaning “to seek out.” Writing a research paper requires you to seek out information about a subject, take a stand on it, and back it up with the opinions, ideas, and views of others. What results is a printed paper variously known as a term paper or library paper, usually between five and fifteen pages long—most instructors specify a minimum length—in which you present your views and findings on the chosen subject.

It is not a secret that the majority of students hate writing a research paper. The reason is simple it steals your time and energy. Not to mention, constant anxiety that you will not be able to meet the deadline or that you will forget about some academic requirement.

We will not lie to you; a research paper is a difficult assignment. You will have to spend a lot of time. You will need to read, to analyze, and to search for the material. You will probably be stuck sometimes. However, if you organize your work smart, you will gain something that is worth all the effort – knowledge, experience, and high grades.

The reason why many students fail writing a research paper is that nobody explained them how to start and how to plan their work. Luckily, you have found our writing service and we are ready to shed the light on this dark matter.

We have created a step by step guide for you on how to write a research paper. We will dwell upon the structure, the writing tips, the writing strategies as well as academic requirements. Read this whole article and you will see that you can handle writing this assignment and our team of writers is here to assist you.

How to Start a Research Paper?

It all starts with the assignment. Your professor gives you the task. It may be either some general issue or specific topic to write about. Your assignment is your first guide to success. If you understand what you need to do according to the assignment, you are on the road to high results. Do not be scared to clarify your task if you need to. There is nothing wrong in asking a question if you want to do something right. You can ask your professor or you can ask our writers who know a thing or two in academic writing.

It is essential to understand the assignment. A good beginning makes a good ending, so start smart.

Learn how to start a research paper .

Choosing a Topic for a Research Paper

We have already mentioned that it is not enough to do great research. You need to persuade the reader that you have made some great research. What convinces better that an eye-catching topic? That is why it is important to understand how to choose a topic for a research paper.

First, you need to delimit the general idea to a more specific one. Secondly, you need to find what makes this topic interesting for you and for the academia. Finally, you need to refine you topic. Remember, it is not something you will do in one day. You can be reshaping your topic throughout your whole writing process. Still, reshaping not changing it completely. That is why keep in your head one main idea: your topic should be precise and compelling .

Learn how to choose a topic for a research paper .

How to Write a Proposal for a Research Paper?

If you do not know what a proposal is, let us explain it to you. A proposal should answer three main questions:

• What is the main aim of your investigation?
• Why is your investigation important?
• How are you going to achieve the results?

In other words, proposal should show why your topic is interesting and how you are going to prove it. As to writing requirements, they may differ. That is why make sure you find out all the details at your department. You can ask your departmental administrator or find information online at department’s site. It is crucial to follow all the administrative requirements, as it will influence your grade.

Learn how to write a proposal for a research paper .

How to Write a Research Plan?

The next step is writing a plan. You have already decided on the main issues, you have chosen the bibliography, and you have clarified the methods. Here comes the planning. If you want to avoid writer’s block, you have to structure you work. Discuss your strategies and ideas with your instructor. Think thoroughly why you need to present some data and ideas first and others second. Remember that there are basic structure elements that your research paper should include:

• Thesis Statement
• Introduction
• Bibliography

You should keep in mind this skeleton when planning your work. This will keep your mind sharp and your ideas will flow logically.

Learn how to write a research plan .

How to Do Research?

Your research will include three stages: collecting data, reading and analyzing it, and writing itself.

First, you need to collect all the material that you will need for you investigation: films, documents, surveys, interviews, and others. Secondly, you will have to read and analyze. This step is tricky, as you need to do this part smart. It is not enough just to read, as you cannot keep in mind all the information. It is essential that you make notes and write down your ideas while analyzing some data. When you get down to the stage number three, writing itself, you will already have the main ideas written on your notes. Plus, remember to jot down the reference details. You will then appreciate this trick when you will have to write the bibliography.

If you do your research this way, it will be much easier for you to write the paper. You will already have blocks of your ideas written down and you will just need to add some material and refine your paper.

Learn how to do research .

How to Write an Outline for a Research Paper?

To make your paper well organized you need to write an outline. Your outline will serve as your guiding star through the writing process. With a great outline you will not get sidetracked, because you will have a structured plan to follow. Both you and the reader will benefit from your outline. You present your ideas logically and you make your writing coherent according to your plan. As a result, this outline guides the reader through your paper and the reader enjoys the way you demonstrate your ideas.

Learn how to write an outline for a research paper . See research paper outline examples .

How to Write a Thesis Statement for a Research Paper?

Briefly, the thesis is the main argument of your research paper. It should be precise, convincing and logical. Your thesis statement should include your point of view supported by evidence or logic. Still, remember it should be precise. You should not beat around the bush, or provide all the possible evidence you have found. It is usually a single sentence that shows your argument. In on sentence you should make a claim, explain why it significant and convince the reader that your point of view is important.

Learn how to write a thesis statement for a research paper . See research paper thesis statement examples .

Should I Write a Rough Draft for a Research Paper?

Do you know any writer who put their ideas on paper, then never edited them and just published? Probably, no writer did so. Writing a research paper is no exception. It is impossible to cope with this assignment without writing a rough draft.

Your draft will help you understand what you need to polish to make your paper perfect. All the requirements, academic standards make it difficult to do everything flawlessly at the first attempt. Make sure you know all the formatting requirements: margins, words quantity, reference requirements, formatting styles etc.

Learn how to write a rough draft for a research paper .

How to Write an Introduction for a Research Paper?

Let us make it more vivid for you. We have narrowed down the tips on writing an introduction to the three main ones:

• Include your thesis in your introduction

Remember to include the thesis statement in your introduction. Usually, it goes at the end of the first paragraph.

• Present the main ideas of the body

You should tell the main topics you are going to discuss in the main body. For this reason, before writing this part of introduction, make sure you know what is your main body is going to be about. It should include your main ideas.

• Polish your thesis and introduction

When you finish the main body of your paper, come back to the thesis statement and introduction. Restate something if needed. Just make it perfect; because introduction is like the trailer to your paper, it should make the reader want to read the whole piece.

Learn how to write an introduction for a research paper . See research paper introduction examples .

How to Write a Body of a Research Paper?

A body is the main part of your research paper. In this part, you will include all the needed evidence; you will provide the examples and support your argument.

It is important to structure your paragraphs thoroughly. That is to say, topic sentence and the evidence supporting the topic. Stay focused and do not be sidetracked. You have your outline, so follow it.

Here are the main tips to keep in head when writing a body of a research paper:

• Let the ideas flow logically
• Include only relevant information
• Provide the evidence
• Structure the paragraphs
• Make the coherent transition from one paragraph to another

See? When it is all structured, it is not as scary as it seemed at the beginning. Still, if you have doubts, you can always ask our writers for help.

Learn how to write a body of a research paper . See research paper transition examples .

How to Write a Conclusion for a Research Paper?

Writing a good conclusion is important as writing any other part of the paper. Remember that conclusion is not a summary of what you have mentioned before. A good conclusion should include your last strong statement.

If you have written everything according to the plan, the reader already knows why your investigation is important. The reader has already seen the evidence. The only thing left is a strong concluding thought that will organize all your findings.

Never include any new information in conclusion. You need to conclude, not to start a new discussion.

Learn how to write a conclusion for a research paper .

How to Write an Abstract for a Research Paper?

An abstract is a brief summary of your paper, usually 100-200 words. You should provide the main gist of your paper in this short summary. An abstract can be informative, descriptive or proposal. Depending on the type of abstract, you need to write, the requirements will differ.

To write an informative abstract you have to provide the summary of the whole paper. Informative summary. In other words, you need to tell about the main points of your work, the methods used, the results and the conclusion of your research.

To write a descriptive abstract you will not have to provide any summery. You should write a short teaser of your paper. That is to say, you need to write an overview of your paper. The aim of a descriptive abstract is to interest the reader.

Finally, to write a proposal abstract you will need to write the basic summary as for the informative abstract. However, the difference is the following: you aim at persuading someone to let you write on the topic. That is why, a proposal abstract should present your topic as the one worth investigating.

Learn how to write an abstract for a research paper .

Should I Revise and Edit a Research Paper?

Revising and editing your paper is essential if you want to get high grades. Let us help you revise your paper smart:

• Check your paper for spelling and grammar mistakes
• Sharpen the vocabulary
• Make sure there are no slang words in your paper
• Examine your paper in terms of structure
• Compare your topic, thesis statement to the whole piece
• Check your paper for plagiarism

If you need assistance with proofreading and editing your paper, you can turn to the professional editors at our service. They will help you polish your paper to perfection.

Learn how to revise and edit a research paper .

How to Write a Bibliography for a Research Paper?

First, let us make it clear that bibliography and works cited are two different things. Works cited are those that you cited in your paper. Bibliography should include all the materials you used to do your research. Still, remember that bibliography requirements differ depending on the formatting style of your paper. For this reason, make sure you ask you professor all the requirements you need to meet to avoid any misunderstanding.

Learn how to write a bibliography for a research paper .

The Key Secret to a Good Research Paper

Now when you know all the stages of writing a research paper, you are ready to find the key to a good research paper:

• Choose the topic that really interests you
• Make the topic interesting for you even if it is not at the beginning
• Follow the step by step guide and do not get sidetracked
• Be persistent and believe in yourself
• Really do research and write your paper from scratch
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Writing Research Papers

• Research Paper Structure

Whether you are writing a B.S. Degree Research Paper or completing a research report for a Psychology course, it is highly likely that you will need to organize your research paper in accordance with American Psychological Association (APA) guidelines.  Here we discuss the structure of research papers according to APA style.

Major Sections of a Research Paper in APA Style

A complete research paper in APA style that is reporting on experimental research will typically contain a Title page, Abstract, Introduction, Methods, Results, Discussion, and References sections. 1  Many will also contain Figures and Tables and some will have an Appendix or Appendices.  These sections are detailed as follows (for a more in-depth guide, please refer to " How to Write a Research Paper in APA Style ”, a comprehensive guide developed by Prof. Emma Geller). 2

What is this paper called and who wrote it? – the first page of the paper; this includes the name of the paper, a “running head”, authors, and institutional affiliation of the authors.  The institutional affiliation is usually listed in an Author Note that is placed towards the bottom of the title page.  In some cases, the Author Note also contains an acknowledgment of any funding support and of any individuals that assisted with the research project.

One-paragraph summary of the entire study – typically no more than 250 words in length (and in many cases it is well shorter than that), the Abstract provides an overview of the study.

Introduction

What is the topic and why is it worth studying? – the first major section of text in the paper, the Introduction commonly describes the topic under investigation, summarizes or discusses relevant prior research (for related details, please see the Writing Literature Reviews section of this website), identifies unresolved issues that the current research will address, and provides an overview of the research that is to be described in greater detail in the sections to follow.

What did you do? – a section which details how the research was performed.  It typically features a description of the participants/subjects that were involved, the study design, the materials that were used, and the study procedure.  If there were multiple experiments, then each experiment may require a separate Methods section.  A rule of thumb is that the Methods section should be sufficiently detailed for another researcher to duplicate your research.

What did you find? – a section which describes the data that was collected and the results of any statistical tests that were performed.  It may also be prefaced by a description of the analysis procedure that was used. If there were multiple experiments, then each experiment may require a separate Results section.

What is the significance of your results? – the final major section of text in the paper.  The Discussion commonly features a summary of the results that were obtained in the study, describes how those results address the topic under investigation and/or the issues that the research was designed to address, and may expand upon the implications of those findings.  Limitations and directions for future research are also commonly addressed.

List of articles and any books cited – an alphabetized list of the sources that are cited in the paper (by last name of the first author of each source).  Each reference should follow specific APA guidelines regarding author names, dates, article titles, journal titles, journal volume numbers, page numbers, book publishers, publisher locations, websites, and so on (for more information, please see the Citing References in APA Style page of this website).

Tables and Figures

Graphs and data (optional in some cases) – depending on the type of research being performed, there may be Tables and/or Figures (however, in some cases, there may be neither).  In APA style, each Table and each Figure is placed on a separate page and all Tables and Figures are included after the References.   Tables are included first, followed by Figures.   However, for some journals and undergraduate research papers (such as the B.S. Research Paper or Honors Thesis), Tables and Figures may be embedded in the text (depending on the instructor’s or editor’s policies; for more details, see "Deviations from APA Style" below).

Supplementary information (optional) – in some cases, additional information that is not critical to understanding the research paper, such as a list of experiment stimuli, details of a secondary analysis, or programming code, is provided.  This is often placed in an Appendix.

Variations of Research Papers in APA Style

Although the major sections described above are common to most research papers written in APA style, there are variations on that pattern.  These variations include: 

• Literature reviews – when a paper is reviewing prior published research and not presenting new empirical research itself (such as in a review article, and particularly a qualitative review), then the authors may forgo any Methods and Results sections. Instead, there is a different structure such as an Introduction section followed by sections for each of the different aspects of the body of research being reviewed, and then perhaps a Discussion section. 
• Multi-experiment papers – when there are multiple experiments, it is common to follow the Introduction with an Experiment 1 section, itself containing Methods, Results, and Discussion subsections. Then there is an Experiment 2 section with a similar structure, an Experiment 3 section with a similar structure, and so on until all experiments are covered.  Towards the end of the paper there is a General Discussion section followed by References.  Additionally, in multi-experiment papers, it is common for the Results and Discussion subsections for individual experiments to be combined into single “Results and Discussion” sections.

Departures from APA Style

In some cases, official APA style might not be followed (however, be sure to check with your editor, instructor, or other sources before deviating from standards of the Publication Manual of the American Psychological Association).  Such deviations may include:

• Placement of Tables and Figures  – in some cases, to make reading through the paper easier, Tables and/or Figures are embedded in the text (for example, having a bar graph placed in the relevant Results section). The embedding of Tables and/or Figures in the text is one of the most common deviations from APA style (and is commonly allowed in B.S. Degree Research Papers and Honors Theses; however you should check with your instructor, supervisor, or editor first). 
• Incomplete research – sometimes a B.S. Degree Research Paper in this department is written about research that is currently being planned or is in progress. In those circumstances, sometimes only an Introduction and Methods section, followed by References, is included (that is, in cases where the research itself has not formally begun).  In other cases, preliminary results are presented and noted as such in the Results section (such as in cases where the study is underway but not complete), and the Discussion section includes caveats about the in-progress nature of the research.  Again, you should check with your instructor, supervisor, or editor first.
• Class assignments – in some classes in this department, an assignment must be written in APA style but is not exactly a traditional research paper (for instance, a student asked to write about an article that they read, and to write that report in APA style). In that case, the structure of the paper might approximate the typical sections of a research paper in APA style, but not entirely.  You should check with your instructor for further guidelines.

Workshops and Downloadable Resources

• For in-person discussion of the process of writing research papers, please consider attending this department’s “Writing Research Papers” workshop (for dates and times, please check the undergraduate workshops calendar).

Downloadable Resources

• How to Write APA Style Research Papers (a comprehensive guide) [ PDF ]
• Tips for Writing APA Style Research Papers (a brief summary) [ PDF ]
• Example APA Style Research Paper (for B.S. Degree – empirical research) [ PDF ]
• Example APA Style Research Paper (for B.S. Degree – literature review) [ PDF ]

Further Resources

How-To Videos     

• Writing Research Paper Videos

APA Journal Article Reporting Guidelines

• Appelbaum, M., Cooper, H., Kline, R. B., Mayo-Wilson, E., Nezu, A. M., & Rao, S. M. (2018). Journal article reporting standards for quantitative research in psychology: The APA Publications and Communications Board task force report . American Psychologist , 73 (1), 3.
• Levitt, H. M., Bamberg, M., Creswell, J. W., Frost, D. M., Josselson, R., & Suárez-Orozco, C. (2018). Journal article reporting standards for qualitative primary, qualitative meta-analytic, and mixed methods research in psychology: The APA Publications and Communications Board task force report . American Psychologist , 73 (1), 26.  

External Resources

• Formatting APA Style Papers in Microsoft Word
• How to Write an APA Style Research Paper from Hamilton University
• WikiHow Guide to Writing APA Research Papers
• Sample APA Formatted Paper with Comments
• Sample APA Formatted Paper
• Tips for Writing a Paper in APA Style

1 VandenBos, G. R. (Ed). (2010). Publication manual of the American Psychological Association (6th ed.) (pp. 41-60).  Washington, DC: American Psychological Association.

2 geller, e. (2018).  how to write an apa-style research report . [instructional materials]. , prepared by s. c. pan for ucsd psychology.

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• Formatting Research Papers
• Using Databases and Finding References
• What Types of References Are Appropriate?
• Evaluating References and Taking Notes
• Citing References
• Writing a Literature Review
• Writing Process and Revising
• Improving Scientific Writing
• Academic Integrity and Avoiding Plagiarism
• Writing Research Papers Videos

Writing a Research Paper

This page lists some of the stages involved in writing a library-based research paper.

Although this list suggests that there is a simple, linear process to writing such a paper, the actual process of writing a research paper is often a messy and recursive one, so please use this outline as a flexible guide.

Discovering, Narrowing, and Focusing a Researchable Topic

• Try to find a topic that truly interests you
• Try writing your way to a topic
• Talk with your course instructor and classmates about your topic
• Pose your topic as a question to be answered or a problem to be solved

Finding, Selecting, and Reading Sources

You will need to look at the following types of sources:

• library catalog, periodical indexes, bibliographies, suggestions from your instructor
• primary vs. secondary sources
• journals, books, other documents

Grouping, Sequencing, and Documenting Information

The following systems will help keep you organized:

• a system for noting sources on bibliography cards
• a system for organizing material according to its relative importance
• a system for taking notes

Writing an Outline and a Prospectus for Yourself

Consider the following questions:

• What is the topic?
• Why is it significant?
• What background material is relevant?
• What is my thesis or purpose statement?
• What organizational plan will best support my purpose?

Writing the Introduction

In the introduction you will need to do the following things:

• present relevant background or contextual material
• define terms or concepts when necessary
• explain the focus of the paper and your specific purpose
• reveal your plan of organization

Writing the Body

• Use your outline and prospectus as flexible guides
• Build your essay around points you want to make (i.e., don’t let your sources organize your paper)
• Integrate your sources into your discussion
• Summarize, analyze, explain, and evaluate published work rather than merely reporting it
• Move up and down the “ladder of abstraction” from generalization to varying levels of detail back to generalization

Writing the Conclusion

• If the argument or point of your paper is complex, you may need to summarize the argument for your reader.
• If prior to your conclusion you have not yet explained the significance of your findings or if you are proceeding inductively, use the end of your paper to add your points up, to explain their significance.
• Move from a detailed to a general level of consideration that returns the topic to the context provided by the introduction.
• Perhaps suggest what about this topic needs further research.

Revising the Final Draft

• Check overall organization : logical flow of introduction, coherence and depth of discussion in body, effectiveness of conclusion.
• Paragraph level concerns : topic sentences, sequence of ideas within paragraphs, use of details to support generalizations, summary sentences where necessary, use of transitions within and between paragraphs.
• Sentence level concerns: sentence structure, word choices, punctuation, spelling.
• Documentation: consistent use of one system, citation of all material not considered common knowledge, appropriate use of endnotes or footnotes, accuracy of list of works cited.

Academic and Professional Writing

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Analysis Papers

Reading Poetry

A Short Guide to Close Reading for Literary Analysis

Using Literary Quotations

Play Reviews

Writing a Rhetorical Précis to Analyze Nonfiction Texts

Incorporating Interview Data

Grant Proposals

Planning and Writing a Grant Proposal: The Basics

Additional Resources for Grants and Proposal Writing

Job Materials and Application Essays

Writing Personal Statements for Ph.D. Programs

• Before you begin: useful tips for writing your essay
• Guided brainstorming exercises
• Get more help with your essay
• Frequently Asked Questions

Resume Writing Tips

CV Writing Tips

Cover Letters

Business Letters

Proposals and Dissertations

Resources for Proposal Writers

Resources for Dissertators

Research Papers

Planning and Writing Research Papers

Quoting and Paraphrasing

Writing Annotated Bibliographies

Creating Poster Presentations

Writing an Abstract for Your Research Paper

Thank-You Notes

Advice for Students Writing Thank-You Notes to Donors

Reading for a Review

Critical Reviews

Writing a Review of Literature

Scientific Reports

Scientific Report Format

Sample Lab Assignment

Writing for the Web

Writing an Effective Blog Post

Writing for Social Media: A Guide for Academics

• Academic Skills
• Reading, writing and referencing

Research reports

This resource will help you identify the common elements and basic format of a research report.

Research reports generally follow a similar structure and have common elements, each with a particular purpose. Learn more about each of these elements below.

Common elements of reports

Your title should be brief, topic-specific, and informative, clearly indicating the purpose and scope of your study. Include key words in your title so that search engines can easily access your work. For example:  Measurement of water around Station Pier.

An abstract is a concise summary that helps readers to quickly assess the content and direction of your paper. It should be brief, written in a single paragraph and cover: the scope and purpose of your report; an overview of methodology; a summary of the main findings or results; principal conclusions or significance of the findings; and recommendations made.

The information in the abstract must be presented in the same order as it is in your report. The abstract is usually written last when you have developed your arguments and synthesised the results.

The introduction creates the context for your research. It should provide sufficient background to allow the reader to understand and evaluate your study without needing to refer to previous publications. After reading the introduction your reader should understand exactly what your research is about, what you plan to do, why you are undertaking this research and which methods you have used. Introductions generally include:

• The rationale for the present study. Why are you interested in this topic? Why is this topic worth investigating?
• Key terms and definitions.
• An outline of the research questions and hypotheses; the assumptions or propositions that your research will test.

Not all research reports have a separate literature review section. In shorter research reports, the review is usually part of the Introduction.

A literature review is a critical survey of recent relevant research in a particular field. The review should be a selection of carefully organised, focused and relevant literature that develops a narrative ‘story’ about your topic. Your review should answer key questions about the literature:

• What is the current state of knowledge on the topic?
• What differences in approaches / methodologies are there?
• Where are the strengths and weaknesses of the research?
• What further research is needed? The review may identify a gap in the literature which provides a rationale for your study and supports your research questions and methodology.

The review is not just a summary of all you have read. Rather, it must develop an argument or a point of view that supports your chosen methodology and research questions.

The purpose of this section is to detail how you conducted your research so that others can understand and replicate your approach.

You need to briefly describe the subjects (if appropriate), any equipment or materials used and the approach taken. If the research method or method of data analysis is commonly used within your field of study, then simply reference the procedure. If, however, your methods are new or controversial then you need to describe them in more detail and provide a rationale for your approach. The methodology is written in the past tense and should be as concise as possible.

This section is a concise, factual summary of your findings, listed under headings appropriate to your research questions. It’s common to use tables and graphics. Raw data or details about the method of statistical analysis used should be included in the Appendices.

Present your results in a consistent manner. For example, if you present the first group of results as percentages, it will be confusing for the reader and difficult to make comparisons of data if later results are presented as fractions or as decimal values.

In general, you won’t discuss your results here. Any analysis of your results usually occurs in the Discussion section.

Notes on visual data representation:

• Graphs and tables may be used to reveal trends in your data, but they must be explained and referred to in adjacent accompanying text.
• Figures and tables do not simply repeat information given in the text: they summarise, amplify or complement it.
• Graphs are always referred to as ‘Figures’, and both axes must be clearly labelled.
• Tables must be numbered, and they must be able to stand-alone or make sense without your reader needing to read all of the accompanying text.

The Discussion responds to the hypothesis or research question. This section is where you interpret your results, account for your findings and explain their significance within the context of other research. Consider the adequacy of your sampling techniques, the scope and long-term implications of your study, any problems with data collection or analysis and any assumptions on which your study was based. This is also the place to discuss any disappointing results and address limitations.

Checklist for the discussion

• To what extent was each hypothesis supported?
• To what extent are your findings validated or supported by other research?
• Were there unexpected variables that affected your results?
• On reflection, was your research method appropriate?
• Can you account for any differences between your results and other studies?

Conclusions in research reports are generally fairly short and should follow on naturally from points raised in the Discussion. In this section you should discuss the significance of your findings. To what extent and in what ways are your findings useful or conclusive? Is further research required? If so, based on your research experience, what suggestions could you make about improvements to the scope or methodology of future studies?

Also, consider the practical implications of your results and any recommendations you could make. For example, if your research is on reading strategies in the primary school classroom, what are the implications of your results for the classroom teacher? What recommendations could you make for teachers?

A Reference List contains all the resources you have cited in your work, while a Bibliography is a wider list containing all the resources you have consulted (but not necessarily cited) in the preparation of your work. It is important to check which of these is required, and the preferred format, style of references and presentation requirements of your own department.

Appendices (singular ‘Appendix’) provide supporting material to your project. Examples of such materials include:

• Relevant letters to participants and organisations (e.g. regarding the ethics or conduct of the project).
• Background reports.
• Detailed calculations.

Different types of data are presented in separate appendices. Each appendix must be titled, labelled with a number or letter, and referred to in the body of the report.

Appendices are placed at the end of a report, and the contents are generally not included in the word count.

Fi nal ti p

While there are many common elements to research reports, it’s always best to double check the exact requirements for your task. You may find that you don’t need some sections, can combine others or have specific requirements about referencing, formatting or word limits.

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Research Writing ~ How to Write a Research Paper

• Choosing A Topic
• Critical Thinking
• Domain Names
• Starting Your Research
• Writing Tips
• Parts of the Paper
• Edit & Rewrite
• Citations This link opens in a new window

Papers should have a beginning, a middle, and an end. Your introductory paragraph should grab the reader's attention, state your main idea and how you will support it. The body of the paper should expand on what you have stated in the introduction. Finally, the conclusion restates the paper's thesis and should explain what you have learned, giving a wrap up of your main ideas.   

1. The Title The title should be specific and indicate the theme of the research and what ideas it addresses. Use keywords that help explain your paper's topic to the reader. Try to avoid  abbreviations  and  jargon.  Think about keywords that people would use to search for your paper and include them in your title. 

2. The Abstract The abstract is used by readers to get a quick overview of your paper. Typically, they are about 200 words in length (120 words minimum to  250 words maximum). The abstract should introduce the topic and thesis, and should provide a general statement about what you have found in your research. The abstract allows you to mention each major aspect of you topic and helps readers decide whether they want to read the rest of the paper. Because it is a summary of the entire research paper, it is often written last. 

3. The Introduction The introduction should be designed to attract the reader's attention and explain the focus of the research. You will introduce your overview of the topic, your main points of information, and why this subject is important. You can introduce the current understanding and background information about the topic. Toward the end of the introduction, you add your thesis statement, and explain how you will provide information to support your research questions. This provides the purpose, focus, and structure for the rest of the paper.

4. Thesis Statement Most papers will have a thesis statement or main idea and supporting facts/ideas/arguments. State your main idea (something of interest or something to be proven or argued for or against) as your thesis statement, and then provide  supporting facts and arguments. A thesis statement is a declarative sentence that asserts the position a paper will be taking. It also points toward the paper's development. This statement should be both specific and arguable. Generally, the thesis statement will be placed at the end of the first paragraph of your paper. The remainder of your paper will support this thesis.

Students often learn to write a thesis as a first step in the writing process, but often, after research, a writers viewpoint may change. Therefore a thesis statement may be one of the final steps in writing. 

Examples of thesis statements from Purdue OWL. . .

5. The Literature Review The purpose of the literature review is to describe past important research and how it specifically relates to the research thesis. It should be a synthesis of the previous literature and the new idea being researched. The review should examine the major theories related to the topic to date and their contributors. It should include all relevant findings from credible sources, such as academic books and peer-reviewed journal articles. You will want  to:

• Explain how the literature helps the researcher understand the topic.
• Try to show connections and any disparities between the literature.
• Identify new ways to interpret prior research.
• Reveal any gaps that exist in the literature.

More about writing a literature review. . .  from The Writing Center at UNC-Chapel Hill More about summarizing. . . from the Center for Writing Studies at the University of Illinois-Urbana Champaign

6. The Discussion ​The purpose of the discussion is to interpret and describe what you have learned from your research. Make the reader understand why your topic is important. The discussion should always demonstrate what you have learned from your readings (and viewings) and how that learning has made the topic evolve, especially from the short description of main points in the introduction. Explain any new understanding or insights you have had after reading your articles and/or books. Paragraphs should use transitioning sentences to develop how one paragraph idea leads to the next. The discussion will always connect to the introduction, your thesis statement, and the literature you reviewed, but it does not simply repeat or rearrange the introduction. You want to: 

• Demonstrate critical thinking, not just reporting back facts that you gathered.
• If possible, tell how the topic has evolved over the past and give it's implications for the future.
• Fully explain your main ideas with supporting information.
• Explain why your thesis is correct giving arguments to counter points.

​7. The Conclusion A concluding paragraph is a brief summary of your main ideas and restates the paper's main thesis, giving the reader the sense that the stated goal of the paper has been accomplished. What have you learned by doing this research that you didn't know before? What conclusions have you drawn? You may also want to suggest further areas of study, improvement of research possibilities, etc. to demonstrate your critical thinking regarding your research.

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• Research paper

Writing a Research Paper Introduction | Step-by-Step Guide

Published on September 24, 2022 by Jack Caulfield . Revised on September 5, 2024.

The introduction to a research paper is where you set up your topic and approach for the reader. It has several key goals:

• Present your topic and get the reader interested
• Provide background or summarize existing research
• Position your own approach
• Detail your specific research problem and problem statement
• Give an overview of the paper’s structure

The introduction looks slightly different depending on whether your paper presents the results of original empirical research or constructs an argument by engaging with a variety of sources.

The five steps in this article will help you put together an effective introduction for either type of research paper.

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Table of contents

Step 1: introduce your topic, step 2: describe the background, step 3: establish your research problem, step 4: specify your objective(s), step 5: map out your paper, research paper introduction examples, frequently asked questions about the research paper introduction.

The first job of the introduction is to tell the reader what your topic is and why it’s interesting or important. This is generally accomplished with a strong opening hook.

The hook is a striking opening sentence that clearly conveys the relevance of your topic. Think of an interesting fact or statistic, a strong statement, a question, or a brief anecdote that will get the reader wondering about your topic.

For example, the following could be an effective hook for an argumentative paper about the environmental impact of cattle farming:

A more empirical paper investigating the relationship of Instagram use with body image issues in adolescent girls might use the following hook:

Don’t feel that your hook necessarily has to be deeply impressive or creative. Clarity and relevance are still more important than catchiness. The key thing is to guide the reader into your topic and situate your ideas.

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This part of the introduction differs depending on what approach your paper is taking.

In a more argumentative paper, you’ll explore some general background here. In a more empirical paper, this is the place to review previous research and establish how yours fits in.

Argumentative paper: Background information

After you’ve caught your reader’s attention, specify a bit more, providing context and narrowing down your topic.

Provide only the most relevant background information. The introduction isn’t the place to get too in-depth; if more background is essential to your paper, it can appear in the body .

Empirical paper: Describing previous research

For a paper describing original research, you’ll instead provide an overview of the most relevant research that has already been conducted. This is a sort of miniature literature review —a sketch of the current state of research into your topic, boiled down to a few sentences.

This should be informed by genuine engagement with the literature. Your search can be less extensive than in a full literature review, but a clear sense of the relevant research is crucial to inform your own work.

Begin by establishing the kinds of research that have been done, and end with limitations or gaps in the research that you intend to respond to.

The next step is to clarify how your own research fits in and what problem it addresses.

Argumentative paper: Emphasize importance

In an argumentative research paper, you can simply state the problem you intend to discuss, and what is original or important about your argument.

Empirical paper: Relate to the literature

In an empirical research paper, try to lead into the problem on the basis of your discussion of the literature. Think in terms of these questions:

• What research gap is your work intended to fill?
• What limitations in previous work does it address?
• What contribution to knowledge does it make?

You can make the connection between your problem and the existing research using phrases like the following.

Now you’ll get into the specifics of what you intend to find out or express in your research paper.

The way you frame your research objectives varies. An argumentative paper presents a thesis statement, while an empirical paper generally poses a research question (sometimes with a hypothesis as to the answer).

Argumentative paper: Thesis statement

The thesis statement expresses the position that the rest of the paper will present evidence and arguments for. It can be presented in one or two sentences, and should state your position clearly and directly, without providing specific arguments for it at this point.

Empirical paper: Research question and hypothesis

The research question is the question you want to answer in an empirical research paper.

Present your research question clearly and directly, with a minimum of discussion at this point. The rest of the paper will be taken up with discussing and investigating this question; here you just need to express it.

A research question can be framed either directly or indirectly.

• This study set out to answer the following question: What effects does daily use of Instagram have on the prevalence of body image issues among adolescent girls?
• We investigated the effects of daily Instagram use on the prevalence of body image issues among adolescent girls.

If your research involved testing hypotheses , these should be stated along with your research question. They are usually presented in the past tense, since the hypothesis will already have been tested by the time you are writing up your paper.

For example, the following hypothesis might respond to the research question above:

The final part of the introduction is often dedicated to a brief overview of the rest of the paper.

In a paper structured using the standard scientific “introduction, methods, results, discussion” format, this isn’t always necessary. But if your paper is structured in a less predictable way, it’s important to describe the shape of it for the reader.

If included, the overview should be concise, direct, and written in the present tense.

• This paper will first discuss several examples of survey-based research into adolescent social media use, then will go on to …
• This paper first discusses several examples of survey-based research into adolescent social media use, then goes on to …

Scribbr’s paraphrasing tool can help you rephrase sentences to give a clear overview of your arguments.

Full examples of research paper introductions are shown in the tabs below: one for an argumentative paper, the other for an empirical paper.

• Argumentative paper
• Empirical paper

Are cows responsible for climate change? A recent study (RIVM, 2019) shows that cattle farmers account for two thirds of agricultural nitrogen emissions in the Netherlands. These emissions result from nitrogen in manure, which can degrade into ammonia and enter the atmosphere. The study’s calculations show that agriculture is the main source of nitrogen pollution, accounting for 46% of the country’s total emissions. By comparison, road traffic and households are responsible for 6.1% each, the industrial sector for 1%. While efforts are being made to mitigate these emissions, policymakers are reluctant to reckon with the scale of the problem. The approach presented here is a radical one, but commensurate with the issue. This paper argues that the Dutch government must stimulate and subsidize livestock farmers, especially cattle farmers, to transition to sustainable vegetable farming. It first establishes the inadequacy of current mitigation measures, then discusses the various advantages of the results proposed, and finally addresses potential objections to the plan on economic grounds.

The rise of social media has been accompanied by a sharp increase in the prevalence of body image issues among women and girls. This correlation has received significant academic attention: Various empirical studies have been conducted into Facebook usage among adolescent girls (Tiggermann & Slater, 2013; Meier & Gray, 2014). These studies have consistently found that the visual and interactive aspects of the platform have the greatest influence on body image issues. Despite this, highly visual social media (HVSM) such as Instagram have yet to be robustly researched. This paper sets out to address this research gap. We investigated the effects of daily Instagram use on the prevalence of body image issues among adolescent girls. It was hypothesized that daily Instagram use would be associated with an increase in body image concerns and a decrease in self-esteem ratings.

The introduction of a research paper includes several key elements:

• A hook to catch the reader’s interest
• Relevant background on the topic
• Details of your research problem

and your problem statement

• A thesis statement or research question
• Sometimes an overview of the paper

Don’t feel that you have to write the introduction first. The introduction is often one of the last parts of the research paper you’ll write, along with the conclusion.

This is because it can be easier to introduce your paper once you’ve already written the body ; you may not have the clearest idea of your arguments until you’ve written them, and things can change during the writing process .

The way you present your research problem in your introduction varies depending on the nature of your research paper . A research paper that presents a sustained argument will usually encapsulate this argument in a thesis statement .

A research paper designed to present the results of empirical research tends to present a research question that it seeks to answer. It may also include a hypothesis —a prediction that will be confirmed or disproved by your research.

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• Research Report: Definition, Types + [Writing Guide]

One of the reasons for carrying out research is to add to the existing body of knowledge. Therefore, when conducting research, you need to document your processes and findings in a research report. 

With a research report, it is easy to outline the findings of your systematic investigation and any gaps needing further inquiry. Knowing how to create a detailed research report will prove useful when you need to conduct research.  

What is a Research Report?

A research report is a well-crafted document that outlines the processes, data, and findings of a systematic investigation. It is an important document that serves as a first-hand account of the research process, and it is typically considered an objective and accurate source of information.

In many ways, a research report can be considered as a summary of the research process that clearly highlights findings, recommendations, and other important details. Reading a well-written research report should provide you with all the information you need about the core areas of the research process.

Features of a Research Report 

So how do you recognize a research report when you see one? Here are some of the basic features that define a research report. 

• It is a detailed presentation of research processes and findings, and it usually includes tables and graphs. 
• It is written in a formal language.
• A research report is usually written in the third person.
• It is informative and based on first-hand verifiable information.
• It is formally structured with headings, sections, and bullet points.
• It always includes recommendations for future actions. 

Types of Research Report 

The research report is classified based on two things; nature of research and target audience.

Nature of Research

• Qualitative Research Report

This is the type of report written for qualitative research . It outlines the methods, processes, and findings of a qualitative method of systematic investigation. In educational research, a qualitative research report provides an opportunity for one to apply his or her knowledge and develop skills in planning and executing qualitative research projects.

A qualitative research report is usually descriptive in nature. Hence, in addition to presenting details of the research process, you must also create a descriptive narrative of the information.

• Quantitative Research Report

A quantitative research report is a type of research report that is written for quantitative research. Quantitative research is a type of systematic investigation that pays attention to numerical or statistical values in a bid to find answers to research questions. 

In this type of research report, the researcher presents quantitative data to support the research process and findings. Unlike a qualitative research report that is mainly descriptive, a quantitative research report works with numbers; that is, it is numerical in nature. 

Target Audience

Also, a research report can be said to be technical or popular based on the target audience. If you’re dealing with a general audience, you would need to present a popular research report, and if you’re dealing with a specialized audience, you would submit a technical report. 

• Technical Research Report

A technical research report is a detailed document that you present after carrying out industry-based research. This report is highly specialized because it provides information for a technical audience; that is, individuals with above-average knowledge in the field of study. 

In a technical research report, the researcher is expected to provide specific information about the research process, including statistical analyses and sampling methods. Also, the use of language is highly specialized and filled with jargon. 

Examples of technical research reports include legal and medical research reports. 

• Popular Research Report

A popular research report is one for a general audience; that is, for individuals who do not necessarily have any knowledge in the field of study. A popular research report aims to make information accessible to everyone. 

It is written in very simple language, which makes it easy to understand the findings and recommendations. Examples of popular research reports are the information contained in newspapers and magazines. 

Importance of a Research Report 

• Knowledge Transfer: As already stated above, one of the reasons for carrying out research is to contribute to the existing body of knowledge, and this is made possible with a research report. A research report serves as a means to effectively communicate the findings of a systematic investigation to all and sundry.  
• Identification of Knowledge Gaps: With a research report, you’d be able to identify knowledge gaps for further inquiry. A research report shows what has been done while hinting at other areas needing systematic investigation. 
• In market research, a research report would help you understand the market needs and peculiarities at a glance. 
• A research report allows you to present information in a precise and concise manner. 
• It is time-efficient and practical because, in a research report, you do not have to spend time detailing the findings of your research work in person. You can easily send out the report via email and have stakeholders look at it. 

Guide to Writing a Research Report

A lot of detail goes into writing a research report, and getting familiar with the different requirements would help you create the ideal research report. A research report is usually broken down into multiple sections, which allows for a concise presentation of information.

Structure and Example of a Research Report

This is the title of your systematic investigation. Your title should be concise and point to the aims, objectives, and findings of a research report. 

• Table of Contents

This is like a compass that makes it easier for readers to navigate the research report.

An abstract is an overview that highlights all important aspects of the research including the research method, data collection process, and research findings. Think of an abstract as a summary of your research report that presents pertinent information in a concise manner. 

An abstract is always brief; typically 100-150 words and goes straight to the point. The focus of your research abstract should be the 5Ws and 1H format – What, Where, Why, When, Who and How. 

• Introduction

Here, the researcher highlights the aims and objectives of the systematic investigation as well as the problem which the systematic investigation sets out to solve. When writing the report introduction, it is also essential to indicate whether the purposes of the research were achieved or would require more work.

In the introduction section, the researcher specifies the research problem and also outlines the significance of the systematic investigation. Also, the researcher is expected to outline any jargons and terminologies that are contained in the research.  

• Literature Review

A literature review is a written survey of existing knowledge in the field of study. In other words, it is the section where you provide an overview and analysis of different research works that are relevant to your systematic investigation. 

It highlights existing research knowledge and areas needing further investigation, which your research has sought to fill. At this stage, you can also hint at your research hypothesis and its possible implications for the existing body of knowledge in your field of study. 

• An Account of Investigation

This is a detailed account of the research process, including the methodology, sample, and research subjects. Here, you are expected to provide in-depth information on the research process including the data collection and analysis procedures. 

In a quantitative research report, you’d need to provide information surveys, questionnaires and other quantitative data collection methods used in your research. In a qualitative research report, you are expected to describe the qualitative data collection methods used in your research including interviews and focus groups. 

In this section, you are expected to present the results of the systematic investigation. 

This section further explains the findings of the research, earlier outlined. Here, you are expected to present a justification for each outcome and show whether the results are in line with your hypotheses or if other research studies have come up with similar results.

• Conclusions

This is a summary of all the information in the report. It also outlines the significance of the entire study. 

• References and Appendices

This section contains a list of all the primary and secondary research sources. 

Tips for Writing a Research Report

• Define the Context for the Report

As is obtainable when writing an essay, defining the context for your research report would help you create a detailed yet concise document. This is why you need to create an outline before writing so that you do not miss out on anything. 

• Define your Audience

Writing with your audience in mind is essential as it determines the tone of the report. If you’re writing for a general audience, you would want to present the information in a simple and relatable manner. For a specialized audience, you would need to make use of technical and field-specific terms. 

• Include Significant Findings

The idea of a research report is to present some sort of abridged version of your systematic investigation. In your report, you should exclude irrelevant information while highlighting only important data and findings. 

• Include Illustrations

Your research report should include illustrations and other visual representations of your data. Graphs, pie charts, and relevant images lend additional credibility to your systematic investigation.

• Choose the Right Title

A good research report title is brief, precise, and contains keywords from your research. It should provide a clear idea of your systematic investigation so that readers can grasp the entire focus of your research from the title. 

• Proofread the Report

Before publishing the document, ensure that you give it a second look to authenticate the information. If you can, get someone else to go through the report, too, and you can also run it through proofreading and editing software. 

How to Gather Research Data for Your Report  

• Understand the Problem

Every research aims at solving a specific problem or set of problems, and this should be at the back of your mind when writing your research report. Understanding the problem would help you to filter the information you have and include only important data in your report. 

• Know what your report seeks to achieve

This is somewhat similar to the point above because, in some way, the aim of your research report is intertwined with the objectives of your systematic investigation. Identifying the primary purpose of writing a research report would help you to identify and present the required information accordingly. 

• Identify your audience

Knowing your target audience plays a crucial role in data collection for a research report. If your research report is specifically for an organization, you would want to present industry-specific information or show how the research findings are relevant to the work that the company does. 

• Create Surveys/Questionnaires

A survey is a research method that is used to gather data from a specific group of people through a set of questions. It can be either quantitative or qualitative. 

A survey is usually made up of structured questions, and it can be administered online or offline. However, an online survey is a more effective method of research data collection because it helps you save time and gather data with ease. 

You can seamlessly create an online questionnaire for your research on Formplus . With the multiple sharing options available in the builder, you would be able to administer your survey to respondents in little or no time. 

Formplus also has a report summary too l that you can use to create custom visual reports for your research.

Step-by-step guide on how to create an online questionnaire using Formplus  

• Sign into Formplus

In the Formplus builder, you can easily create different online questionnaires for your research by dragging and dropping preferred fields into your form. To access the Formplus builder, you will need to create an account on Formplus. 

Once you do this, sign in to your account and click on Create new form to begin. 

• Edit Form Title : Click on the field provided to input your form title, for example, “Research Questionnaire.”
• Edit Form : Click on the edit icon to edit the form.
• Add Fields : Drag and drop preferred form fields into your form in the Formplus builder inputs column. There are several field input options for questionnaires in the Formplus builder. 
• Edit fields
• Click on “Save”
• Form Customization: With the form customization options in the form builder, you can easily change the outlook of your form and make it more unique and personalized. Formplus allows you to change your form theme, add background images, and even change the font according to your needs. 
• Multiple Sharing Options: Formplus offers various form-sharing options, which enables you to share your questionnaire with respondents easily. You can use the direct social media sharing buttons to share your form link to your organization’s social media pages.  You can also send out your survey form as email invitations to your research subjects too. If you wish, you can share your form’s QR code or embed it on your organization’s website for easy access. 

Conclusion  

Always remember that a research report is just as important as the actual systematic investigation because it plays a vital role in communicating research findings to everyone else. This is why you must take care to create a concise document summarizing the process of conducting any research. 

In this article, we’ve outlined essential tips to help you create a research report. When writing your report, you should always have the audience at the back of your mind, as this would set the tone for the document. 

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13.1 Formatting a Research Paper

Learning objectives.

• Identify the major components of a research paper written using American Psychological Association (APA) style.
• Apply general APA style and formatting conventions in a research paper.

In this chapter, you will learn how to use APA style , the documentation and formatting style followed by the American Psychological Association, as well as MLA style , from the Modern Language Association. There are a few major formatting styles used in academic texts, including AMA, Chicago, and Turabian:

• AMA (American Medical Association) for medicine, health, and biological sciences
• APA (American Psychological Association) for education, psychology, and the social sciences
• Chicago—a common style used in everyday publications like magazines, newspapers, and books
• MLA (Modern Language Association) for English, literature, arts, and humanities
• Turabian—another common style designed for its universal application across all subjects and disciplines

While all the formatting and citation styles have their own use and applications, in this chapter we focus our attention on the two styles you are most likely to use in your academic studies: APA and MLA.

If you find that the rules of proper source documentation are difficult to keep straight, you are not alone. Writing a good research paper is, in and of itself, a major intellectual challenge. Having to follow detailed citation and formatting guidelines as well may seem like just one more task to add to an already-too-long list of requirements.

Following these guidelines, however, serves several important purposes. First, it signals to your readers that your paper should be taken seriously as a student’s contribution to a given academic or professional field; it is the literary equivalent of wearing a tailored suit to a job interview. Second, it shows that you respect other people’s work enough to give them proper credit for it. Finally, it helps your reader find additional materials if he or she wishes to learn more about your topic.

Furthermore, producing a letter-perfect APA-style paper need not be burdensome. Yes, it requires careful attention to detail. However, you can simplify the process if you keep these broad guidelines in mind:

• Work ahead whenever you can. Chapter 11 “Writing from Research: What Will I Learn?” includes tips for keeping track of your sources early in the research process, which will save time later on.
• Get it right the first time. Apply APA guidelines as you write, so you will not have much to correct during the editing stage. Again, putting in a little extra time early on can save time later.
• Use the resources available to you. In addition to the guidelines provided in this chapter, you may wish to consult the APA website at http://www.apa.org or the Purdue University Online Writing lab at http://owl.english.purdue.edu , which regularly updates its online style guidelines.

General Formatting Guidelines

This chapter provides detailed guidelines for using the citation and formatting conventions developed by the American Psychological Association, or APA. Writers in disciplines as diverse as astrophysics, biology, psychology, and education follow APA style. The major components of a paper written in APA style are listed in the following box.

These are the major components of an APA-style paper:

Body, which includes the following:

• Headings and, if necessary, subheadings to organize the content
• In-text citations of research sources
• References page

All these components must be saved in one document, not as separate documents.

The title page of your paper includes the following information:

• Title of the paper
• Author’s name
• Name of the institution with which the author is affiliated
• Header at the top of the page with the paper title (in capital letters) and the page number (If the title is lengthy, you may use a shortened form of it in the header.)

List the first three elements in the order given in the previous list, centered about one third of the way down from the top of the page. Use the headers and footers tool of your word-processing program to add the header, with the title text at the left and the page number in the upper-right corner. Your title page should look like the following example.

The next page of your paper provides an abstract , or brief summary of your findings. An abstract does not need to be provided in every paper, but an abstract should be used in papers that include a hypothesis. A good abstract is concise—about one hundred fifty to two hundred fifty words—and is written in an objective, impersonal style. Your writing voice will not be as apparent here as in the body of your paper. When writing the abstract, take a just-the-facts approach, and summarize your research question and your findings in a few sentences.

In Chapter 12 “Writing a Research Paper” , you read a paper written by a student named Jorge, who researched the effectiveness of low-carbohydrate diets. Read Jorge’s abstract. Note how it sums up the major ideas in his paper without going into excessive detail.

Write an abstract summarizing your paper. Briefly introduce the topic, state your findings, and sum up what conclusions you can draw from your research. Use the word count feature of your word-processing program to make sure your abstract does not exceed one hundred fifty words.

Depending on your field of study, you may sometimes write research papers that present extensive primary research, such as your own experiment or survey. In your abstract, summarize your research question and your findings, and briefly indicate how your study relates to prior research in the field.

Margins, Pagination, and Headings

APA style requirements also address specific formatting concerns, such as margins, pagination, and heading styles, within the body of the paper. Review the following APA guidelines.

Use these general guidelines to format the paper:

• Set the top, bottom, and side margins of your paper at 1 inch.
• Use double-spaced text throughout your paper.
• Use a standard font, such as Times New Roman or Arial, in a legible size (10- to 12-point).
• Use continuous pagination throughout the paper, including the title page and the references section. Page numbers appear flush right within your header.
• Section headings and subsection headings within the body of your paper use different types of formatting depending on the level of information you are presenting. Additional details from Jorge’s paper are provided.

Begin formatting the final draft of your paper according to APA guidelines. You may work with an existing document or set up a new document if you choose. Include the following:

• Your title page
• The abstract you created in Note 13.8 “Exercise 1”
• Correct headers and page numbers for your title page and abstract

APA style uses section headings to organize information, making it easy for the reader to follow the writer’s train of thought and to know immediately what major topics are covered. Depending on the length and complexity of the paper, its major sections may also be divided into subsections, sub-subsections, and so on. These smaller sections, in turn, use different heading styles to indicate different levels of information. In essence, you are using headings to create a hierarchy of information.

The following heading styles used in APA formatting are listed in order of greatest to least importance:

• Section headings use centered, boldface type. Headings use title case, with important words in the heading capitalized.
• Subsection headings use left-aligned, boldface type. Headings use title case.
• The third level uses left-aligned, indented, boldface type. Headings use a capital letter only for the first word, and they end in a period.
• The fourth level follows the same style used for the previous level, but the headings are boldfaced and italicized.
• The fifth level follows the same style used for the previous level, but the headings are italicized and not boldfaced.

Visually, the hierarchy of information is organized as indicated in Table 13.1 “Section Headings” .

Table 13.1 Section Headings

A college research paper may not use all the heading levels shown in Table 13.1 “Section Headings” , but you are likely to encounter them in academic journal articles that use APA style. For a brief paper, you may find that level 1 headings suffice. Longer or more complex papers may need level 2 headings or other lower-level headings to organize information clearly. Use your outline to craft your major section headings and determine whether any subtopics are substantial enough to require additional levels of headings.

Working with the document you developed in Note 13.11 “Exercise 2” , begin setting up the heading structure of the final draft of your research paper according to APA guidelines. Include your title and at least two to three major section headings, and follow the formatting guidelines provided above. If your major sections should be broken into subsections, add those headings as well. Use your outline to help you.

Because Jorge used only level 1 headings, his Exercise 3 would look like the following:

Citation Guidelines

In-text citations.

Throughout the body of your paper, include a citation whenever you quote or paraphrase material from your research sources. As you learned in Chapter 11 “Writing from Research: What Will I Learn?” , the purpose of citations is twofold: to give credit to others for their ideas and to allow your reader to follow up and learn more about the topic if desired. Your in-text citations provide basic information about your source; each source you cite will have a longer entry in the references section that provides more detailed information.

In-text citations must provide the name of the author or authors and the year the source was published. (When a given source does not list an individual author, you may provide the source title or the name of the organization that published the material instead.) When directly quoting a source, it is also required that you include the page number where the quote appears in your citation.

This information may be included within the sentence or in a parenthetical reference at the end of the sentence, as in these examples.

Epstein (2010) points out that “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive” (p. 137).

Here, the writer names the source author when introducing the quote and provides the publication date in parentheses after the author’s name. The page number appears in parentheses after the closing quotation marks and before the period that ends the sentence.

Addiction researchers caution that “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive” (Epstein, 2010, p. 137).

Here, the writer provides a parenthetical citation at the end of the sentence that includes the author’s name, the year of publication, and the page number separated by commas. Again, the parenthetical citation is placed after the closing quotation marks and before the period at the end of the sentence.

As noted in the book Junk Food, Junk Science (Epstein, 2010, p. 137), “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive.”

Here, the writer chose to mention the source title in the sentence (an optional piece of information to include) and followed the title with a parenthetical citation. Note that the parenthetical citation is placed before the comma that signals the end of the introductory phrase.

David Epstein’s book Junk Food, Junk Science (2010) pointed out that “junk food cannot be considered addictive in the same way that we think of psychoactive drugs as addictive” (p. 137).

Another variation is to introduce the author and the source title in your sentence and include the publication date and page number in parentheses within the sentence or at the end of the sentence. As long as you have included the essential information, you can choose the option that works best for that particular sentence and source.

Citing a book with a single author is usually a straightforward task. Of course, your research may require that you cite many other types of sources, such as books or articles with more than one author or sources with no individual author listed. You may also need to cite sources available in both print and online and nonprint sources, such as websites and personal interviews. Chapter 13 “APA and MLA Documentation and Formatting” , Section 13.2 “Citing and Referencing Techniques” and Section 13.3 “Creating a References Section” provide extensive guidelines for citing a variety of source types.

Writing at Work

APA is just one of several different styles with its own guidelines for documentation, formatting, and language usage. Depending on your field of interest, you may be exposed to additional styles, such as the following:

• MLA style. Determined by the Modern Languages Association and used for papers in literature, languages, and other disciplines in the humanities.
• Chicago style. Outlined in the Chicago Manual of Style and sometimes used for papers in the humanities and the sciences; many professional organizations use this style for publications as well.
• Associated Press (AP) style. Used by professional journalists.

References List

The brief citations included in the body of your paper correspond to the more detailed citations provided at the end of the paper in the references section. In-text citations provide basic information—the author’s name, the publication date, and the page number if necessary—while the references section provides more extensive bibliographical information. Again, this information allows your reader to follow up on the sources you cited and do additional reading about the topic if desired.

The specific format of entries in the list of references varies slightly for different source types, but the entries generally include the following information:

• The name(s) of the author(s) or institution that wrote the source
• The year of publication and, where applicable, the exact date of publication
• The full title of the source
• For books, the city of publication
• For articles or essays, the name of the periodical or book in which the article or essay appears
• For magazine and journal articles, the volume number, issue number, and pages where the article appears
• For sources on the web, the URL where the source is located

The references page is double spaced and lists entries in alphabetical order by the author’s last name. If an entry continues for more than one line, the second line and each subsequent line are indented five spaces. Review the following example. ( Chapter 13 “APA and MLA Documentation and Formatting” , Section 13.3 “Creating a References Section” provides extensive guidelines for formatting reference entries for different types of sources.)

In APA style, book and article titles are formatted in sentence case, not title case. Sentence case means that only the first word is capitalized, along with any proper nouns.

Key Takeaways

• Following proper citation and formatting guidelines helps writers ensure that their work will be taken seriously, give proper credit to other authors for their work, and provide valuable information to readers.
• Working ahead and taking care to cite sources correctly the first time are ways writers can save time during the editing stage of writing a research paper.
• APA papers usually include an abstract that concisely summarizes the paper.
• APA papers use a specific headings structure to provide a clear hierarchy of information.
• In APA papers, in-text citations usually include the name(s) of the author(s) and the year of publication.
• In-text citations correspond to entries in the references section, which provide detailed bibliographical information about a source.

Writing for Success Copyright © 2015 by University of Minnesota is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License , except where otherwise noted.

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• A Research Guide
• Research Paper Guide

Research Paper Body Paragraph Structure

Introduction.

• Referrences
• Ways to start paragraph
• Step by step guide
• Research paragraph examples

Learning the basics of a paragraph structure

• Title (cover page).
• Introduction.
• Literature review.
• Research methodology.
• Data analysis.
• Conclusion.
• Reference page.

5 winning ways to start a body paragraph

• Topic Sentence : it should provide a clear focus and introduce the specific aspect you will discuss. For example, “One key factor influencing climate change is…”.
• Opening Statement: grab your readers’ attention with a thought-provoking or surprising statement related to your topic. For instance, “The alarming increase in global temperatures has reached a critical point, demanding immediate action.”
• Quotation: find a relevant quote from a reputable source. It won’t only add credibility to your research but will also engage the reader right from the start.
• Anecdote or example: start your academic paragraph with a funny story or a real-world example that illustrates the significance of your research topic.
• Background information : provide a brief background or context for the topic you are about to discuss. For example, “In recent years, the prevalence of cyber-attacks has skyrocketed, posing a severe threat to individuals, organizations, and even national security.”

A step-by-step guide to starting a concise body paragraph

Step 1: introduce the main point or argument., step 2: provide evidence or examples., step 3: explain and analyze., step 4: connect to the main argument., step 5: review and revise., flawless body paragraph example: how does it look.

• Topic Sentence: Rising global temperatures have significant implications for ecosystems and biodiversity.
• Evidence/Example 1: According to a study by the Intergovernmental Panel on Climate Change (IPCC), global average temperatures have increased by 1.1 degrees Celsius since pre-industrial times (IPCC, 2021). This temperature rise has led to melting polar ice caps and glaciers, rising sea levels, and coastal erosion (Smith et al., 2019).
• Explanation/Analysis 1: The significant increase in global temperatures has caused observable changes in the Earth’s physical environment. The melting of polar ice caps not only contributes to the rise in sea levels but also disrupts marine ecosystems.
• Evidence/Example 2: In addition to the loss of coastal habitats, higher temperatures have also resulted in shifts in the geographical distribution of species. Research by Parmesan and Yohe (2019) indicates that many plant and animal species have altered their ranges and migration patterns in response to changing climate conditions.
• Explanation/Analysis 2: The observed shifts in species distribution highlight the vulnerability of ecosystems to climate change. As temperature zone modification, species that cannot adapt or migrate to suitable habitats may face reduced reproductive success and increased risk of extinction.
• Connect to the main argument: These examples demonstrate that the rising global temperatures associated with climate change have profound implications for ecosystems and biodiversity.

The bottom line

• Writing a Research Paper
• Research Paper Title
• Research Paper Sources
• Research Paper Problem Statement
• Research Paper Thesis Statement
• Hypothesis for a Research Paper
• Research Question
• Research Paper Outline
• Research Paper Summary
• Research Paper Prospectus
• Research Paper Proposal
• Research Paper Format
• Research Paper Styles
• AMA Style Research Paper
• MLA Style Research Paper
• Chicago Style Research Paper
• APA Style Research Paper
• Research Paper Structure
• Research Paper Cover Page
• Research Paper Abstract
• Research Paper Introduction
• Research Paper Body Paragraph
• Research Paper Literature Review
• Research Paper Background
• Research Paper Methods Section
• Research Paper Results Section
• Research Paper Discussion Section
• Research Paper Conclusion
• Research Paper Appendix
• Research Paper Bibliography
• APA Reference Page
• Annotated Bibliography
• Bibliography vs Works Cited vs References Page
• Research Paper Types
• What is Qualitative Research

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Body Paragraphs

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Body paragraphs: Moving from general to specific information

Your paper should be organized in a manner that moves from general to specific information. Every time you begin a new subject, think of an inverted pyramid - The broadest range of information sits at the top, and as the paragraph or paper progresses, the author becomes more and more focused on the argument ending with specific, detailed evidence supporting a claim. Lastly, the author explains how and why the information she has just provided connects to and supports her thesis (a brief wrap-up or warrant).

Moving from General to Specific Information

The four elements of a good paragraph (TTEB)

A good paragraph should contain at least the following four elements: T ransition, T opic sentence, specific E vidence and analysis, and a B rief wrap-up sentence (also known as a warrant ) –TTEB!

• A T ransition sentence leading in from a previous paragraph to assure smooth reading. This acts as a hand-off from one idea to the next.
• A T opic sentence that tells the reader what you will be discussing in the paragraph.
• Specific E vidence and analysis that supports one of your claims and that provides a deeper level of detail than your topic sentence.
• A B rief wrap-up sentence that tells the reader how and why this information supports the paper’s thesis. The brief wrap-up is also known as the warrant. The warrant is important to your argument because it connects your reasoning and support to your thesis, and it shows that the information in the paragraph is related to your thesis and helps defend it.

Supporting evidence (induction and deduction)

Induction is the type of reasoning that moves from specific facts to a general conclusion. When you use induction in your paper, you will state your thesis (which is actually the conclusion you have come to after looking at all the facts) and then support your thesis with the facts. The following is an example of induction taken from Dorothy U. Seyler’s Understanding Argument :

There is the dead body of Smith. Smith was shot in his bedroom between the hours of 11:00 p.m. and 2:00 a.m., according to the coroner. Smith was shot with a .32 caliber pistol. The pistol left in the bedroom contains Jones’s fingerprints. Jones was seen, by a neighbor, entering the Smith home at around 11:00 p.m. the night of Smith’s death. A coworker heard Smith and Jones arguing in Smith’s office the morning of the day Smith died.

Conclusion: Jones killed Smith.

Here, then, is the example in bullet form:

• Conclusion: Jones killed Smith
• Support: Smith was shot by Jones’ gun, Jones was seen entering the scene of the crime, Jones and Smith argued earlier in the day Smith died.
• Assumption: The facts are representative, not isolated incidents, and thus reveal a trend, justifying the conclusion drawn.

When you use deduction in an argument, you begin with general premises and move to a specific conclusion. There is a precise pattern you must use when you reason deductively. This pattern is called syllogistic reasoning (the syllogism). Syllogistic reasoning (deduction) is organized in three steps:

• Major premise
• Minor premise

In order for the syllogism (deduction) to work, you must accept that the relationship of the two premises lead, logically, to the conclusion. Here are two examples of deduction or syllogistic reasoning:

• Major premise: All men are mortal.
• Minor premise: Socrates is a man.
• Conclusion: Socrates is mortal.
• Major premise: People who perform with courage and clear purpose in a crisis are great leaders.
• Minor premise: Lincoln was a person who performed with courage and a clear purpose in a crisis.
• Conclusion: Lincoln was a great leader.

So in order for deduction to work in the example involving Socrates, you must agree that (1) all men are mortal (they all die); and (2) Socrates is a man. If you disagree with either of these premises, the conclusion is invalid. The example using Socrates isn’t so difficult to validate. But when you move into more murky water (when you use terms such as courage , clear purpose , and great ), the connections get tenuous.

For example, some historians might argue that Lincoln didn’t really shine until a few years into the Civil War, after many Union losses to Southern leaders such as Robert E. Lee.

The following is a clear example of deduction gone awry:

• Major premise: All dogs make good pets.
• Minor premise: Doogle is a dog.
• Conclusion: Doogle will make a good pet.

If you don’t agree that all dogs make good pets, then the conclusion that Doogle will make a good pet is invalid.

When a premise in a syllogism is missing, the syllogism becomes an enthymeme. Enthymemes can be very effective in argument, but they can also be unethical and lead to invalid conclusions. Authors often use enthymemes to persuade audiences. The following is an example of an enthymeme:

If you have a plasma TV, you are not poor.

The first part of the enthymeme (If you have a plasma TV) is the stated premise. The second part of the statement (you are not poor) is the conclusion. Therefore, the unstated premise is “Only rich people have plasma TVs.” The enthymeme above leads us to an invalid conclusion (people who own plasma TVs are not poor) because there are plenty of people who own plasma TVs who are poor. Let’s look at this enthymeme in a syllogistic structure:

• Major premise: People who own plasma TVs are rich (unstated above).
• Minor premise: You own a plasma TV.
• Conclusion: You are not poor.

To help you understand how induction and deduction can work together to form a solid argument, you may want to look at the United States Declaration of Independence. The first section of the Declaration contains a series of syllogisms, while the middle section is an inductive list of examples. The final section brings the first and second sections together in a compelling conclusion.

Cut up and leased out, the bodies of the poor suffer a final indignity in Texas

The University of North Texas Health Science Center built a flourishing business using hundreds of unclaimed corpses. It suspended the program after NBC News exposed failures to treat the dead and their families with respect.

DALLAS — Long before his bleak final years, when he struggled with mental illness and lived mostly on the streets, Victor Carl Honey joined the Army, serving honorably for nearly a decade. And so, when his heart gave out and he died alone 30 years later, he was entitled to a burial with military honors.

Instead, without his consent or his family’s knowledge, the Dallas County Medical Examiner’s Office gave his body to a state medical school, where it was frozen, cut into pieces and leased out across the country.

A Swedish medical device maker paid $341 for access to Honey’s severed right leg to train clinicians to harvest veins using its surgical tool. A medical education company spent $900 to send his torso to Pittsburgh so trainees could practice implanting a spine stimulator. And the U.S. Army paid $210 to use a pair of bones from his skull to educate military medical personnel at a hospital near San Antonio.

In the name of scientific advancement, clinical education and fiscal expediency, the bodies of the destitute in the Dallas-Fort Worth region have been routinely collected from hospital beds, nursing homes and homeless encampments and used for training or research without their consent — and often without the approval of any survivors, an NBC News investigation found.

Honey, who died in September 2022, is one of about 2,350 people whose unclaimed bodies have been given to the Fort Worth-based University of North Texas Health Science Center since 2019 under agreements with Dallas and Tarrant counties . Among these, more than 830 bodies were selected by the center for dissection and study. After the medical school and other groups were finished, the bodies were cremated and, in most cases, interred at area cemeteries or scattered at sea. Some had families who were looking for them.

For months as NBC News reported this article, Health Science Center officials defended their practices, arguing that using unclaimed bodies was essential for training future doctors. But on Friday, after reporters shared detailed findings of this investigation, the center announced it was immediately suspending its body donation program and firing the officials who led it. The center said it was also hiring a consulting firm to investigate the program’s operations.

“As a result of the information brought to light through your inquiries, it has become clear that failures existed in the management and oversight of The University of North Texas Health Science Center’s Willed Body Program,” the statement said. “The program has fallen short of the standards of respect, care and professionalism that we demand.”

Last year, NBC News revealed in its “Lost Rites” investigation that coroners and medical examiners in Mississippi and nationally had repeatedly failed to notify families of their loved ones’ deaths before burying them in pauper’s graveyards . That investigation led reporters to North Texas, where officials had come to view the unclaimed dead not as a costly burden, but as a free resource.

Before its sudden shuttering last week, the Health Science Center’s body business flourished. 

On paper, the arrangements with Dallas and Tarrant counties offered a pragmatic solution to an expensive problem: Local medical examiners and coroners nationwide bear the considerable costs of burying or cremating tens of thousands of unclaimed bodies each year. Disproportionately Black, male, mentally ill and homeless, these are individuals whose family members often cannot be easily reached, or whose relatives cannot or will not pay for cremation or burial.

The University of North Texas Health Science Center used some of these bodies to teach medical students. Others, like Honey’s, were parceled out to for-profit medical training and technology companies — including industry giants like Johnson & Johnson, Boston Scientific and Medtronic — that rely on human remains to develop products and teach doctors how to use them. The Health Science Center advertised the bodies as being of “the highest quality found anywhere in the U.S.”

Do you have a story to share about the use of unclaimed bodies for research? Contact us .

Proponents say using unclaimed bodies transforms a tragic situation into one of hope and service, providing a steady supply of human specimens needed to educate doctors and advance medical research. But for families who later discover their missing relatives were dissected and studied, the news is haunting, compounding their grief and depriving them of the opportunity to mourn.

“The county and the medical school are doing this because it saves them money, but that doesn’t make it right,” said Thomas Champney, an anatomy professor at the University of Miami Miller School of Medicine who researches the ethical use of human bodies . “Since these individuals did not consent, they should not be used in any form or fashion.”

A half-century ago, it was common for U.S. medical schools to use unclaimed bodies, and doing so remains legal in most of the country, including Texas. Many programs have halted the practice in recent years, though, and some states, including Hawaii, Minnesota and Vermont, have flatly prohibited it — part of an evolution of medical ethics that has called on anatomists to treat human specimens with the same dignity shown to living patients.

The University of North Texas Health Science Center charged in the opposite direction.

Through public records requests, NBC News obtained thousands of pages of government records and data documenting the acquisition, dissection and distribution of unclaimed bodies by the center over a five-year period.

An analysis of the material reveals repeated failures by death investigators in Dallas and Tarrant counties — and by the center — to contact family members who were reachable before declaring a body unclaimed. Reporters examined dozens of cases and identified 12 in which families learned weeks, months or years later that a relative had been provided to the medical school, leaving many survivors angry and traumatized.

Five of those families found out what happened from NBC News. Reporters used public records databases, ancestry websites and social media searches to locate and reach them within just a few days, even though county and center officials said they had been unable to find any survivors.

In one case, a man learned of his stepmother’s death and transfer to the center after a real estate agent called about selling her house. In another, Dallas County marked a man’s body as unclaimed and gave it to the Health Science Center, even as his loved ones filed a missing person report and actively searched for him.

From 2023: NBC News’ “Lost Rites” investigation

• After a mother in Jackson, Mississippi, reported her son missing, police kept the truth from her for months.
• ‘They just threw him away’: Another Mississippi man was buried without his family’s knowledge .
• America’s patchwork death notification system routinely leaves families in the dark.
• The Department of Justice took action after a Mississippi coroner buried men without notifying their families.
• The Jackson Police Department adopted a next-of-kin notification policy following NBC News’ reporting.

Before the Health Science Center announced it was suspending the program, officials in the two counties had already told NBC News they were reconsidering their unclaimed body agreements in light of the reporters’ findings. 

Commissioners in Dallas County recently postponed a vote on whether to extend their contract. The top elected official in Tarrant County, Judge Tim O’Hare — who voted to renew the county’s agreement with the center in January — said he planned to explore legal options “to end any and all immoral, unethical, and irresponsible practices stemming from this program.”

“No individual’s remains should be used for medical research, nor sold for profit, without their pre-death consent, or the consent of their next of kin,” O’Hare’s office said . “The idea that families may be unaware that their loved ones’ remains are being used for research without consent is disturbing, to say the least.” 

NBC News also shared its findings with dozens of companies, teaching hospitals and medical schools that have relied on the Health Science Center to supply human specimens. Ten said they did not know the center had provided them with unclaimed bodies. Some, including Medtronic, said they had internal policies requiring consent from the deceased or their legal surrogate.

DePuy Synthes, a Johnson & Johnson company, said it had paused its relationship with the center after learning from a reporter that it had received body parts from four unclaimed people. And Boston Scientific, whose company Relievant Medsystems used the torsos of more than two dozen unclaimed bodies for training on a surgical tool , said it was reviewing its transactions with the center, adding that it had believed the program obtained consent from donors or families.

“We empathize with the families who were not reached as part of this process,” the company said.

The Army said it, too, was examining its reliance on the center and planned to review and clarify internal policies on the use of unclaimed bodies. Under federal contracts totaling about $345,000, the center has provided the Army with dozens of whole bodies, heads and skull bones since 2021 — including at least 21 unclaimed bodies. An Army spokesperson said officials had not considered the possibility that the program hadn’t gotten consent from donors or their families.

The Texas Funeral Service Commission, which regulates body donation programs in the state, is conducting a review of its own. In April, the agency issued a moratorium on out-of-state shipments while it studies a range of issues, including the use of unclaimed bodies by the Health Science Center.

In the case of Victor Honey, it shouldn’t have been hard for Dallas County investigators to find survivors: His son shares his father’s first and last name and lives in the Dallas area. Family members are outraged that no one from the county or the Health Science Center informed them of Honey’s death, much less sought permission to dissect his body and distribute it for training.

It wasn’t until a year and a half after he died that his relatives finally learned that news — from a chance encounter with a stranger struck by the similarity of the father’s and son’s names, followed by a phone call from NBC News.

“It’s like a hole in your soul that can never be filled,” said Brenda Cloud, one of Honey’s sisters. “We feel violated.”

Two years before Honey’s death, Oscar Fitzgerald died of a drug overdose outside a Fort Worth convenience store. County officials failed to reach his siblings or adult children, so they had no voice in deciding whether to donate his body. It was taken to the University of North Texas Health Science Center, pumped with preservatives and assigned to a first-year medical student to study over the coming year.

Five months passed before his family learned from a friend in September 2020 that he was dead. ​​When his brother rushed to Fort Worth to claim the remains, he said he was told by the Health Science Center that he’d have to wait — the program was not done using the body.

Patrick Fitzgerald, who had last seen his 57-year-old brother the previous Thanksgiving, was aghast.

“Now that the family has come forward,” he said, “you mean to tell me we can’t have him?”

Instead, Fitzgerald said he was told his family must fill out donation consent forms to eventually receive his brother’s ashes. A year and a half later — after the body had been leased out a second time, to a Texas dental school — the center billed the family $54.50 in shipping costs for the box that arrived at Fitzgerald’s Arkansas home containing his brother’s remains. He also received a letter from Claudia Yellott, then the manager of UNT’s body donation program.

“UNT Health Science Center and our students value the selfless sacrifice made by your family,” Yellott wrote.

As of Friday, Yellott’s photo and bio were missing from the Health Science Center website, along with those of Rustin Reeves, the longtime director of the center’s anatomy program . Yellott confirmed to NBC News that she had been terminated and declined to comment further. Reeves did not respond to messages. The center declined to specify who was fired. 

The Fitzgeralds’ ordeal was the scenario one Tarrant County commissioner had feared in 2018, when Yellott and Reeves pitched their plan to receive the county’s unclaimed dead.

They described it as a win for everyone: The county would save on burial costs and the center would, as Yellott phrased it , obtain “valuable material” needed to educate future physicians.

The commissioners were elated at the prospect of saving up to a half-million dollars a year. But one, Andy Nguyen, questioned the morality of dissecting bodies of people with no family to consent and raised the possibility of survivors coming forward later, horrified to learn how their relatives were treated.

“Just because they don’t have any next of kin doesn’t mean they have no voice,” Nguyen said .

After the Health Science Center pledged to handle each body with dignity, all five commissioners voted to approve the agreement. A little over a year later, Dallas County struck a similar deal, with one major difference: While Tarrant County families who couldn’t afford to make funeral arrangements were given an option to donate their relatives’ bodies to the center, Dallas County gave survivors no choice.

Soon, a steady stream of bodies began to flow to the center. The program went from receiving 439 bodies in the 2019 fiscal year to nearly 1,400 in 2021 — about a third of them unclaimed dead from Dallas and Tarrant counties. This coincided with a multimillion-dollar expansion and renovation of the Health Science Center’s body storage facilities and laboratories.

The supply of unclaimed dead helped bring in about $2.5 million a year from outside groups, according to financial records . Many of those payments came from medical device makers that spent tens of thousands of dollars to use the center-run laboratory space, BioSkills of North Texas, to train clinicians on how to use their products — a revenue stream made possible by the school’s robust supply of “cadaveric specimens.”

That economic engine has now stalled; the center announced it was permanently closing the BioSkills lab in response to NBC News’ findings. In its statement, the center said it “is committed to addressing all issues and taking corrective actions to maintain public trust.”

The partnerships with Dallas and Tarrant counties, which drew little attention when they were adopted, quietly rippled through the community of professionals who work with the dead and dying in North Texas.

Eli Shupe, a bioethicist at the University of Texas at Arlington, was volunteering with a Tarrant County hospice provider in late 2021 when a chaplain made a comment that rocked her.

“Oh, poor Mr. Smith,” Shupe recalled the chaplain saying. “He doesn’t have long, and then it’s off to the medical school.”

Her shock led Shupe to spend months studying the use of unclaimed bodies in Texas. As she investigated, she pondered a philosophical question: People have the right to make decisions about their bodies while they’re alive, but should that right die with them?

No, she ultimately concluded, it should not.

Shupe herself has signed up to give her body to the Health Science Center when she dies, in part to underscore that she doesn’t oppose body donation. But she emphasized that it was her choice.

“What they’re doing is uncomfortably close to grave-robbing,” she said.

Shupe was alluding to the dark history, long before voluntary body-donation programs, when U.S. medical schools turned to “resurrectionists,” or “body snatchers,” who dug up the graves of poor and formerly enslaved people. To curb this ghastly 19th-century practice, states adopted laws giving schools authority to use unclaimed bodies for student training and experiments.

Many of those laws remain on the books, but the medical community has largely moved beyond them. Last year, the American Association for Anatomy released guidelines for human body donation stating that “programs should not accept unclaimed or unidentified individuals into their programs as a matter of justice.”

Experts said the Health Science Center appeared to be an outlier in terms of the number of unclaimed bodies it used. No national data exists on this issue, so NBC News surveyed more than 50 major U.S. medical schools. Each of the 44 that answered said they don’t use unclaimed bodies — and some condemned doing so.

Joy Balta, an anatomist who runs a body donation program at Point Loma Nazarene University, chaired the committee that wrote the anatomy association’s new guidelines. He said using unclaimed bodies violates basic principles of dignity and consent now embraced by most experts in his field.

One reason that bodies should come only from consenting donors, Balta and others note: Some religions have strict views about how the dead should be treated.

“We don’t know if the individual is completely against their body being donated, and we can’t just disregard that,” Balta said.

Since 2021, dozens of entities have received unclaimed bodies from the Health Science Center — including some, like the University of Arkansas for Medical Sciences, that explicitly prohibit the practice on ethical grounds. 

The Little Rock-based school received shipments of skull bones and heads in 2023 and 2024 that included parts harvested from unclaimed bodies, records show. Leslie Taylor, a University of Arkansas medical school spokesperson, said because the UNT office that provided specimens is called the Willed Body Program , officials “believed they came from donors who willed their remains for education and study.”

Taylor said the school would adopt procedures to ensure it receives bodies only from people who have given explicit permission.

Before abruptly suspending the program last week, the Health Science Center had vigorously defended its practices. 

“An unclaimed individual is incapable of consenting to any process after death, which includes burial, donation, cremation, eco-burials or any other use of the body,” the center had said in a statement on Aug. 16. “If a relative is not located or does not claim the remains, a decision must still be made.”

Shupe argued that it’s problematic for a public medical school to benefit from the deaths of the “very poor” in its community. She has now embarked on a campaign to end the use of unclaimed bodies in Texas and nationally.

After publishing a newspaper essay criticizing the practice, she brought her concerns directly to the Tarrant County Commissioners Court at a meeting last year, asking officials to consider the message being sent to marginalized residents and people of color. 

“How does it look,” she said , “when a Black body is dissected with nobody’s permission at all, simply because they died poor?”

All Victor Honey’s family has to go by are faded memories, a handful of keepsakes, online snapshots and a trail of court records spanning eight states and Washington, D.C. These clues tell a disjointed story of an Army veteran tormented by paranoid delusions who repeatedly rejected help as he slid into homelessness and whose body went unclaimed, despite having a family who cared deeply for him.

His two sisters remember Honey teaching them math, making them laugh, shielding them from bullies and helping raise them when their parents divorced and moved the family from Mississippi to Cleveland in the 1970s. He was meticulous, hardworking, well-dressed — and in search of a calling.

After starting college, Honey joined the Army in late 1984 and reported to Texas’ Fort Hood, where he trained as a medic and, at a military club, danced with a soon-to-be Air Force enlistee named Kimberly. They married not long after and had a daughter. A son followed.

The young family lived at the base until 1988, when Honey’s enlistment ended. He then joined the Army Reserves in Dallas and was called up to support the first Gulf War. Though he didn’t want to go, he spent four months in Germany, so upset about the deployment that he rarely left his base. He remained angry after he returned home.

Kimberly Patman said Honey had multiple affairs, leading them to separate in 1992, which threw him into a deep depression. He sought mental health services from a local Department of Veterans Affairs facility and was given antipsychotic medication that he quit after a month, saying he was allergic.

From there, his life unraveled.

In 1995, Honey was arrested in Dallas for trespassing. A doctor at the jail called Patman and said he’d had some kind of breakdown. She called his father in Cleveland, who brought him home.

He was diagnosed with paranoid schizophrenia but refused to take the medication that eased his delusional thoughts. He was convinced people were coming after him, barricaded himself in his room and became a compulsive hoarder, filing papers in a leather satchel.

He was off his medications in early 1997 when he stole a car from a dealership and robbed three banks in three states — each time handing a teller a note demanding money. He had no weapon. He was sentenced to three years in federal prison.

After he was released, Honey tried living in Cleveland, but abruptly left.

“He just disappeared,” Patman said. “They didn’t know where he was. We didn’t know where he was. And it was like that for years.”

He eventually drifted to Washington, where he wound up on the streets. He filed more than a dozen lawsuits, claiming an array of grievances. He posted a video to YouTube in which he showed his broken teeth and suggested the police were responsible. “This is a horrendous, horrendous life here in Washington,” he told the camera.

He landed in Dallas again in late 2018. He was arrested multiple times for fare evasion and filing a false police report, and appeared at city council meetings claiming he’d been wrongfully charged. He also pleaded guilty to assaulting an emergency room nurse who was attempting to provide him care.

And then came the phone call that brought the family together again.

In early 2022, a caseworker at a Dallas-area hospital contacted Honey’s daughter, Victoria, in Montgomery, Alabama, to say he was in intensive care and might not survive, the family said. Patman and Victoria rushed to his side and were told his kidneys were failing.

“We’re here, the kids are here, we love you,” Patman told Honey. In response, he opened his eyes and asked, “Why did you divorce me?” They ended up laughing about it.

Brenda Cloud, his sister, called from Cleveland. “I would just talk to him and remind him of growing up and of his children, and he had a lot to fight for,” she said.

Honey’s condition improved, but he ignored advice to go to a nursing home and instead checked himself out. Several weeks later, he got on the phone with his namesake son. They’d often gone years without talking, but the son said he knew his father loved him.

That was Victor Carl Honey’s last contact with his family.

On Sept. 19, 2022, Honey was discovered semiconscious in a wheelchair at a downtown Dallas light rail station and taken to Baylor University Medical Center. He died early the next morning. He was 58.

After a Baylor social worker was unable to find his family, Honey’s body was transported to the Dallas County Medical Examiner’s Office, where an investigator was assigned to find next of kin.

The county investigator sought information from police and area hospitals but was unable to locate relatives. She then turned to the internet, where she found numbers for Patman, Honey’s brother in Ohio, his stepmother and his late father, but she reported they were disconnected. On Oct. 17, 2022, the investigator wrote that her search was complete and no family was found. The medical examiner’s office deemed Honey’s body unclaimed.

That same day, Honey was delivered to the University of North Texas Health Science Center, where he was placed in a freezer, awaiting assignment.

One of the most solemn duties of local government is notifying families when someone dies. Though the world, in so many ways, has never been more connected, finding survivors still can be difficult in an era of growing homelessness and increasingly fractured families. 

Death investigators at the Dallas County Medical Examiner’s Office follow a detailed checklist: They reach out to area hospitals to seek emergency contact information, search missing person reports, and comb public records databases for possible phone numbers. They also call neighbors and homeless shelters. If no family is found, they must sign an affidavit stating they did all they could.

In Tarrant County, officials delegated the primary responsibility for contacting next of kin to the Health Science Center, which said it takes similar steps.

But these efforts repeatedly fell short.

For two and a half years, Fran Moore of Lodi, New York, didn’t know what happened to her 79-year-old father, Carl Yenner. She cried when an NBC News reporter notified her in February that he had died at a Dallas hospital in May 2021 and his body had been sent to the Health Science Center.

Moore said she and her brother had struggled to stay in touch with their father across the miles. After not hearing from him, her brother filed a missing person report in Wichita Falls, about two hours from Dallas, where Yenner had lived. They still don’t know how he wound up in Dallas, how he died or why nobody contacted them. A Dallas County worker signed a form in June 2021 stating she had completed an exhaustive search for possible relatives.

But after spotting Yenner’s name on a list of unclaimed bodies provided by Dallas County, NBC News quickly identified Moore and her brother as Yenner’s children and found working phone numbers for each of them.

“If you could find us,” Moore said, “why didn’t they?”

Another question left unanswered: Given that Yenner was an Army veteran and entitled to federal burial benefits , what was the economic argument for Dallas County to send his body to the Health Science Center? At least 32 unclaimed veterans, including Honey, have been given to the program since 2020, records show.

After the center was done with Yenner’s body, it was cremated and interred among fellow service members at Dallas-Fort Worth National Cemetery. Moore said she’s heartbroken she couldn’t bury him with the rest of his family in New Jersey.

“To not have any kind of funeral for him,” she said, “for his family to come see him to say goodbye?”

Without commenting on specific cases, Dallas County Administrator Darryl Martin offered condolences to families whose relatives were used by the program. He said his staff works hard to locate family members and treats bodies with dignity. He didn’t address the use of unclaimed veterans.

In January, in an attempt to improve its efforts to find survivors in Tarrant County, the Health Science Center hired a company called The Voice After Life , whose mission is to help governments locate families of the unclaimed. The center said it has found families in about 80% of cases since then; officials did not know the previous success rate.

In a statement issued weeks before announcing it was suspending the program, the center said it “seeks to understand and honor the wishes of the family and deceased.”

It did not, however, honor the wishes of Michael Dewayne Coleman’s relatives. 

Coleman, 43, died alone on Oct. 21, 2023, in a Dallas hospital after possibly being hit by a car. An investigator for the medical examiner signed off on his case file, saying “all reasonable efforts” had been made to find next of kin.

But his relatives should have been easy to reach. More than a week before his death, his fiancée, Louisa Harvey, had filed a missing person report with the Dallas Police Department after he failed to return from a night out with friends, not knowing he was already languishing in a hospital. She spent months searching for him, alongside two of Coleman’s sisters. She printed missing person posters and canvassed neighborhoods near their home.

She said she called the detective assigned to the missing person case almost every day, eventually suspecting that finding Coleman wasn’t a priority because of his criminal record, which included illegal drug use and two domestic violence convictions.

Harvey finally learned of his death in March, after the Dallas County medical examiner listed him as an unclaimed body in the National Missing and Unidentified Persons System, or NamUs , a free federal database meant to connect missing person reports with reports of unclaimed bodies. By the time Harvey found the posting online, the medical examiner had sent Coleman’s body to the Health Science Center.

His family could have learned of his death months earlier if the police detective assigned to find Coleman had listed him as a missing person in NamUs, but records show he never did. In response to questions from NBC News, a Dallas Police spokesperson said the department had opened an internal investigation into the detective’s handling of the case and would implement a policy change to prevent similar mistakes. 

Harvey couldn’t believe Coleman’s body had been donated without the family’s consent — or his. Last year, while filling out an application for a state ID, she said, Coleman had made clear he didn’t want his organs donated because of his distrust of the medical system; she doubts he would have wanted to donate his whole body.

But when Harvey and one of Coleman’s sisters, Shea Coleman, repeatedly asked the medical examiner and the Health Science Center to release his body — or at least to let them view it — they were told no. In June, a worker at the medical examiner’s office wrote in case notes that she spoke to Yellott, the manager of UNT’s body donation program, who told her Coleman was slated to be used in a longer-term course and that his family could receive his remains when the center was finished with him.

In 12 to 24 months.

In August, after NBC News inquired about his case, a Health Science Center official told reporters that Coleman’s body would be cremated and returned to the family much sooner — an abrupt reversal that the center attributed to the Texas Funeral Service Commission’s temporary ban on out-of-state body shipments. Ten days later, the medical examiner called Harvey to let her know Coleman’s ashes were ready to be picked up.

The center’s refusal to let her see her fiancé’s body has made it harder to grieve, Harvey said.

“I’m lying awake every night thinking, ‘Is that my Michael?’” she said. “‘Did he actually die?’”

After Victor Honey’s body arrived at the University of North Texas Health Science Center, the harvesting began.

Depending on how they were to be used, bodies were either frozen or embalmed. Some were left whole and set aside to train students. Others, like Honey’s , were dissected with scalpels and bone saws, to be distributed on the open market.

In November 2022, Honey’s right leg was used in a training at the center paid for by Getinge, a Swedish medical technology company that makes instruments for use in a surgical procedure called endoscopic vein harvest.

In January 2023, a week after the medical examiner’s office reported that Honey was eligible for a veteran’s burial, bones from his skull were shipped to Brooke Army Medical Center at Fort Sam Houston — where Honey had been ordered to report before his Gulf War deployment more than three decades earlier.

In May 2023, the Health Science Center shipped Honey’s torso to Pittsburgh, where the training company National Bioskills Laboratories provided it to a medical product company renting its facilities to teach doctors a pain-relief procedure called spinal cord stimulation.

NBC News informed Getinge, the Army and National Bioskills about the center’s regular use of unclaimed bodies and Honey’s family not providing consent.

Dr. Douglas Hampers, National Bioskills’ CEO and an orthopedic surgeon, said he was disturbed to learn his company has received unclaimed bodies and expressed sympathy for Honey’s family.

While human specimens are crucial for medical advances, Hampers said bodies should not be used without consent. He said his company would ensure that it no longer accepted unclaimed bodies and would adopt policies to make certain future specimens were donated with families’ permission.

“I don’t think you have to violate a family’s rights in order to train physicians,” he said.

A Getinge spokesperson emailed a statement saying only that the company regularly reviews its policies and operations, “including what we expect from our suppliers.”

In a statement, the Army said that if Honey’s remains were procured legally, the use of his body complied with the service’s current policies.

In July 2023, after Honey’s torso had been returned to the Health Science Center, his remains were cremated and later his ashes were brought to the Dallas County medical examiner.

And there they sat, with no one to claim them. Months passed.

In late April, Honey’s son, Victor, was boxing cans at the Dallas food bank where he volunteered when a woman approached him. She’d overheard someone calling out his name. “Do you know someone else named Victor Honey?” she asked him.

The woman said she knew his father when they both stayed at a downtown homeless shelter and had heard he died. Victor didn’t want to believe it. He tried to put it out of his mind. But the next morning, he called his mother and told her what he’d heard. She cried out and burst into tears.

An internet search led Victor to the medical examiner’s office, which confirmed the details of his father’s death and later told him the remains were available to be picked up.

About the same time, NBC News had found Honey’s name on a list of people whose unclaimed bodies were obtained by the Health Science Center. Using public records, a reporter tracked down Patman, Honey’s ex-wife, and sent her a message on Facebook. She responded immediately.

On a call, the reporter broke the news of how Honey’s body was used.

His family was appalled. Patman said she would have argued against Honey being cut apart and studied, noting that he once told her that he didn’t want to be an organ donor. Victor, though, said he might have been open to donating his father’s body for medical research.

“But y’all should have asked us about it,” he said. “They just sent his body parts away.”

When the family gathered in early June to finally lay Honey to rest, many expressed remorse about not being able to help him. They were frustrated to have no say in what happened to his body. And they said they hoped sharing his story would help spare others from similar anguish.

“Victor had a big, strong family,” Patman told family members. “And now we are going to speak for him.”

On a muggy Monday morning, a couple dozen of Honey’s relatives — nieces and nephews, siblings and cousins, Patman and their children — gathered in a pavilion at the Dallas-Fort Worth National Cemetery for the farewell they had long been denied.

A recording of taps played. A soldier knelt in front of Honey’s daughter, Victoria, and handed her a folded U.S. flag “as a symbol of our appreciation of your loved one’s honorable and faithful service.”

After the funeral, Honey’s relatives made their way to Section 40, Grave No. 464, where a crew dug a hole and placed the urn in the ground. They installed a temporary marker that soon would be replaced by a white granite headstone standing among rows of thousands.

Brenda Cloud, Honey’s sister, is furious over what transpired in the 622 days between her brother’s death and his burial. And she wants answers for the others whose bodies were cut up and studied without consent.

“Whether they had family or not,” she said, “every person deserves to have that dignity.”

Mike Hixenbaugh is a senior investigative reporter for NBC News, based in Maryland, and author of "They Came for the Schools."

Jon Schuppe is an enterprise reporter for NBC News, based in New York.

Susan Carroll was a senior enterprise editor for NBC News, based in Houston.

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• Published: 18 September 2024

Glucagon-like peptide-1 receptor: mechanisms and advances in therapy

• Zhikai Zheng 1 , 2   na1 ,
• Yao Zong 3   na1 ,
• Yiyang Ma 1 , 2 ,
• Yucheng Tian   ORCID: orcid.org/0000-0002-5632-9118 1 , 2 ,
• Yidan Pang   ORCID: orcid.org/0000-0002-2286-1069 1 , 2 ,
• Changqing Zhang 1 , 2 &
• Junjie Gao 1 , 2  

Signal Transduction and Targeted Therapy volume  9 , Article number:  234 ( 2024 ) Cite this article

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• Cell biology
• Metabolic disorders

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and is found primarily on the surfaces of various cell types within the human body. This receptor specifically interacts with GLP-1, a key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, and several other crucial biological functions. In recent years, GLP-1 medications have become a focal point in the medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, and broad development prospects. This article thoroughly traces the developmental milestones of GLP-1 drugs, from their initial discovery to their clinical application, detailing the evolution of diverse GLP-1 medications along with their distinct pharmacological properties. Additionally, this paper explores the potential applications of GLP-1 receptor agonists (GLP-1RAs) in fields such as neuroprotection, anti-infection measures, the reduction of various types of inflammation, and the enhancement of cardiovascular function. It provides an in-depth assessment of the effectiveness of GLP-1RAs across multiple body systems-including the nervous, cardiovascular, musculoskeletal, and digestive systems. This includes integrating the latest clinical trial data and delving into potential signaling pathways and pharmacological mechanisms. The primary goal of this article is to emphasize the extensive benefits of using GLP-1RAs in treating a broad spectrum of diseases, such as obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, musculoskeletal inflammation, and various forms of cancer. The ongoing development of new indications for GLP-1 drugs offers promising prospects for further expanding therapeutic interventions, showcasing their significant potential in the medical field.

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Introduction.

In recent years, GLP-1R and its agonists have garnered widespread attention in the medical community. GLP-1R, a core member of the GPCR family, is widely present on the surfaces of various cells in the human body. 1 , 2 By specifically binding to the key hormone GLP-1, it regulates blood glucose levels and lipid metabolism. 3 , 4 This receptor and its agonists hold significant therapeutic potential, reshaping the treatment approaches for multiple diseases, including diabetes, cardiovascular disorders, and neurodegenerative diseases. 5 , 6 , 7 GLP-1 is a peptide produced by the cleavage of proglucagon, mainly synthesized in the intestinal mucosal L-cells, pancreatic islet α-cells, and neurons in the nucleus of the solitary tract. 3 , 4 GLP-1RAs mimic the action of endogenous GLP-1, activating GLP-1R, thereby enhancing insulin secretion, inhibiting glucagon release, delaying gastric emptying, and reducing food intake through central appetite suppression. 8 , 9 , 10 These mechanisms make GLP-1RAs powerful tools for controlling blood glucose and improving metabolic syndrome. Furthermore, their multifaceted mechanisms of action suggest potential applications beyond traditional metabolic disorders. From the discovery of the GLP-1 fragment GLP-1(7-37) to the development of more stable and long-acting GLP-1 analogs, these milestones represent significant breakthroughs in the medical field. 11 , 12 For instance, the success of exenatide has not only spurred the development of potent GLP-1 analogs such as liraglutide and semaglutide but also unveiled the vast potential of GLP-1RAs in treating various systemic diseases. These developments underscore the importance of GLP-1RAs in modern therapeutics. The applications of GLP-1RAs extend far beyond diabetes management. 5

Here we summarized the complex mechanisms of GLP-1RAs and their latest advancements in treating various diseases, such as musculoskeletal inflammation, obesity, cardiovascular diseases, NAFLD, neurodegenerative diseases, and various cancers. We introduce recent studies that demonstrate the remarkable performance of GLP-1RAs in slowing the progression of neurodegenerative diseases, reducing inflammation, and enhancing cardiovascular health. For example, in the treatment of Alzheimer’s diseases (AD) and Parkinson’s diseases (PD), GLP-1RAs have shown potential in slowing disease progression, while their anti-inflammatory properties offer new hope for conditions such as osteoarthritis (OA), rheumatoid arthritis (RA) and cardiovascular diseases. 13 , 14 , 15 By integrating the latest clinical trial data, we explore the efficacy of GLP-1RAs in treating diseases of the nervous, cardiovascular, endocrine, and digestive systems. We show readers that GLP-1RAs have also been found to significantly reduce the risks of heart failure, atherosclerosis (AS), and hypertension, highlighting their broad therapeutic potential. 16 , 17 , 18 , 19 As new indications continue to be developed, GLP-1 drugs demonstrate immense potential in the medical field, with future research expected to expand their therapeutic applications. The comprehensive exploration of their benefits underscores their transformative potential in medicine, positioning them as a promising approach for addressing a wide array of health issues and paving the way for new research and clinical applications.

The future of GLP-1RA therapy is promising. Researchers are developing more efficient formulations, such as long-acting and oral versions, to improve patient compliance and outcomes. With increasing clinical evidence, GLP-1RAs are set to become essential in treating complex and chronic diseases, offering significant health benefits and addressing unmet medical needs, thus enhancing patient quality of life and solidifying their role in future medical advancements.

Review of the history and milestones in GLP-1 research

In 1979, Richard Goodman found that anglerfish are an ideal source for pancreatic mRNA due to their concentrated cells. He extracted mRNA, spliced anglerfish DNA into bacteria, and used radioactive probes to find the somatostatin gene. In 1982, they published a paper in the Proceedings of the National Academy of Sciences (PNAS), revealing that the glucagon precursor gene actually encodes three peptides-glucagon and two new hormones expressed in the intestine. 20 A year later, a research team led by Graeme Bell from Chiron Corporation published two papers in the journal Nature. 21 , 22 They cloned and sequenced the preproglucagon gene, discovering GLP-1 and GLP-2 hormones. The focus shifted to GLP-1, with Svetlana Mojsov identifying its insulin-stimulating fragment, GLP-1(7-37), in 1983. This was inspired by prior GIP (glucose-dependent insulinotropic polypeptide) research, highlighting that besides GIP, other substances in the intestine also stimulate insulin secretion. This finding was later combined with research by Joel Habener and jointly published in JCI. 11 The team of Jens Juul Holst at the University of Copenhagen in Denmark published a report in FEBS Letters, reaching the same conclusion in January 1987. 23 In December 1987, Stephen Bloom’s team confirmed in a Lancet paper that GLP-1(7-36) is a human intestinal hormone that stimulates insulin production in the pancreas and lowers blood sugar. 24 GLP-1, used for treating diabetes, is quickly broken down in the body, requiring high doses that can cause side effects like nausea. This led to the development of new drugs similar to GLP-1 but with a longer-lasting effect. John Eng marked a significant breakthrough; he isolated exendin-4, a peptide from the Gila monster’s venom, which is structurally similar to human GLP-1 but more stable. GLP-1 is degraded in the bloodstream in less than a minute, whereas this peptide, consisting of 39 amino acids, exendin-4, could last for more than two hours. This work was eventually published in the JBC journal in August 1991. 25 In the early 1990s, despite John Eng’s team identifying a potential diabetes treatment in exendin-4, it initially lacked attention and funding for development. Eng personally secured a patent and partnered with Amylin, leading to the FDA-approved diabetes drug exenatide in 2005, the first GLP-1 analog. This sparked further advancements, including Novo Nordisk’s development of more potent analogs like liraglutide and semaglutide, with the latter achieving over $12 billion in sales by 2022. The journey began in the 1980s with research on Gila monster venom, culminating in the discovery of exendin-4, a stable, effective peptide for treating diabetes, demonstrating the progression from initial discovery to blockbuster diabetes medications. In July 2009, they published a paper in Nature Chemical Biology, reporting for the first time that dual agonists targeting GLP-1R and glucagon receptor (GCGR) had a better weight loss effect. 26 This marked a significant advancement in obesity treatment research, especially in combining multiple drug targets. Matthias Tschöp and Richard DiMarchi developed the first dual and triple agonist weight loss drugs. Eli Lilly and Company is currently researching a dual agonist called tirzepatide, which has outperformed semaglutide in phase 3 clinical trials. Additionally, their under-development triple agonist, Retatrutide, has shown unprecedented weight loss effects in phase 2 clinical trials. 16 Matthias Tschöp and his team discovered that dual agonists targeting both GLP-1 and GIP receptors (GIPR) are more effective in treating diabetes than those targeting only GLP-1R. These dual agonists were found to reduce blood sugar and increase insulin secretion in mice, monkeys, and humans. 27 Subsequently, they investigated a triple agonist capable of simultaneously targeting the GLP-1R, the GCGR, and the GIPR. In December 2014, they published a paper in Nature Medicine, showing that the triple agonist’s weight loss effects in mice exceeded those of the dual agonists. 28 (Fig. 1 ).

Growth and Timescale of Medical Publications on GLP-1 and GLP-1RAs. This figure illustrates the number of published articles over time, from 1978 to 2022, related to GLP-1 and GLP-1RAs, along with significant milestones in clinical trials. The data is visualized through three layered area graphs, each representing a different category of publications: research on GLP-1 (red area), GLP-1RAs (blue area), and clinical trials (green area). Key milestones are annotated on the timeline, including the identification of GLP-1 and GLP-2 through gene sequencing in 1983, the extraction of Exendin-4 from Gila monster venom in 1991, and the first FDA approval of a GLP-1 analog, Exenatide, in 2005. Liraglutide’s clinical trials began in 2000 and the drug’s FDA approval in 2010. Notable is the steep increase in the number of publications from 2000 onwards, reflecting a growing interest and development in the field. The peak in 2022 corresponds to GLP-1 drug sales hitting $22 billion, with the approval of semaglutide by the FDA in 2021 and the initiation of the first clinical trial for an oral diabetes drug based on GLP-1 in the same year. This graph underscores the expanding research and clinical importance of GLP-1-related therapies in the treatment of diabetes. The x-axis represents the year, ranging from 1978 to 2023, and the y-axis quantifies the number of published articles, with a scale ranging from 0 to 2500 articles annual. GLP-1RAs are artificial protein formulations that exhibit partial or complete amino acid sequence similarity to endogenous GLP-1 within the human body. These compounds possess enhanced stability, extended half-lives, and heightened biological potency, enabling them to mimic the actions of GLP-1. Ongoing advancements in research and development have resulted in the production of GLP-1RA with increasingly prolonged half-lives

GLP-1 is a peptide hormone generated through the enzymatic breakdown of proglucagon. It is synthesized in L-cells located in the intestinal mucosa, α-cells found in the pancreatic islet, and neurons residing in the nucleus of the solitary tract. 29 GLP-1, an endocrine hormone, is secreted by enteroendocrine L-cells located in the distal jejunum, ileum, and colon in response to nutrient ingestion and neuroendocrine stimulation. It originates from the preproglucagon precursor, which undergoes enzymatic processing within intestinal L-cells, ultimately giving rise to GLP-1(1-37) and GLP-1(7-36) amide or GLP-1(7-37) peptide variants. 30 , 31 GLP-1 is an incretin hormone that plays a pivotal role in the meticulous control of human blood glucose levels. 32 , 33 Nevertheless, its duration of action is rather ephemeral, lasting a mere 1–2 min within the circulatory system under typical physiological conditions. 34 , 35 Subsequently, GLP-1 undergoes enzymatic degradation facilitated by dipeptidyl peptidase IV (DPP-4), leading to the loss of its biological efficacy. 36

GLP-1R, a member of the GPCR family, exhibits specific affinity for GLP-1. It predominantly localizes to the cellular membrane of diverse cell types throughout the human body. 37 Indeed, GLP-1R is present beyond the confines of the pancreas and extends to a multitude of organs and tissues throughout the body. Its extensive distribution and involvement in diverse physiological processes emphasize the important role of GLP-1R beyond the regulation of glucose metabolism. 38 , 39 , 40 The phenotype observed after GLP-1R knockout (KO) includes various physiological and metabolic changes. GLP-1R plays a role in the central nervous system (CNS) regulation of appetite. GLP-1R KO can lead to increased appetite, contributing to weight gain. 1 GLP-1R is involved in regulating both insulin and glucagon secretion, and its knockout can impair pancreatic function, thereby affecting the balance of these hormones and glucose homeostasis. 41 , 42 GLP-1R is expressed in the cardiovascular system, and its knockout has implications for cardiovascular function. 43 , 44 GLP-1R is present in the CNS, and its absence might contribute to alterations in behavior, mood, or cognitive function. 45 , 46

GLP-1RAs result from intricate structural modifications to GLP-1, enabling them to not only replicate the pharmacological functions of GLP-1 but also impede its hydrolysis by DPP-4, thereby extending the drug’s half-life. 47 , 48 These synthetic protein preparations exhibit partial or complete amino acid sequence homology with endogenous GLP-1, rendering them resistant to degradation which resulting in a prolonged half-life and heightened biological activity. 47 , 48 By emulating the biological activity of natural GLP-1, GLP-1RAs effectively fulfill the role of GLP-1, effectively lowering blood glucose levels without increasing the risk of hypoglycemia and demonstrating favorable safety profiles. 49 GLP-1RAs represent a pharmacotherapeutic category of injectable hypoglycemic agents that are sanctioned as adjunctive therapies to diet and exercise for the management of type 2 diabetes mellitus (T2DM) in adult patients and potentially hold promise in addressing other medical conditions. 7 , 50 , 51 As researchers dive deeper into their multifaceted properties, these medications exhibit the potential to offer therapeutic benefits across a spectrum of diseases in human populations.

The development of GLP-1RAs

The Gila monster, which lives in the deserts of the Americas, can eat up to half its own body weight in one sitting, but its blood sugar remains stable, and its metabolic system runs smoothly despite this large amount of food. 52 , 53 In 1992, Dr. John Enn discovered an exopeptide in the saliva of the Gila monster which he named exendin-4. Dr. John found that exenatide is an analog of human GLP-1RA, with 53% homology to human GLP-1RA; exenatide can stimulate human insulin secretion and regulate blood glucose levels in the body. This hormone is not readily degraded by DPP-4 to GLP-1 in the human body and can act for 12 h or longer. 25

In 2005, exenatide was approved by the U.S. Food and Drug Administration (FDA) for use in treating T2DM; 52 thus began the competition between various GLP-1RAs. GLP-1RAs are being developed to be more similar to the natural GLP-1 hormone found in the human body. This is achieved by replacing and modifying specific amino acids in human GLP-1. 54 , 55 By doing so, the resulting product has a higher similarity or homology to the amino acid sequence of human GLP-1. In addition, efforts are being made to extend the duration of action of GLP-1RAs. Currently, some GLP-1RAs require daily injections, which can be inconvenient for patients. Therefore, researchers are working toward developing formulations that can be administered once a week, providing a longer-lasting effect and reducing the frequency of injections. 56 , 57 Furthermore, there is a focus on developing GLP-1RAs that can be taken orally without the need for injections. This oral preparation would offer a more convenient and comfortable option for patients, potentially leading to better treatment compliance. 58 , 59 Overall, the future research direction of GLP-1RAs involves making them more similar to those in the human body, extending their duration of action, and creating oral formulations for easier administration. 60 , 61 These advancements aim to improve patient experience, compliance, and treatment outcomes.

Exenatide is the world’s first GLP-RA product; it was developed in 1995 and approved for marketing in 2005. 60 Liraglutide was subsequently approved for marketing in February 2010, 62 and lixisenatide was approved for marketing in the European Union in 2013 for the treatment of T2DM and in the United States in July 2016. 63 Albiglutide was approved for marketing in the European Union in March 2014 and in the United States in April 2014. 64 Dulaglutide was approved for marketing in the U.S. in September 2014 for the treatment of T2DM 65 ; semaglutide was approved for marketing in the United States in September 2017 66 ; and beinaglutide is a GLP-RA product developed by a Chinese company and was approved for marketing for the treatment of T2DM in China in September 2016. 67 PEG-loxenatide, China’s first long-acting GLP-RA product, was approved for marketing in China in May 2019. 66 (Tables 1 and 2 )

Current GLP-1RAs

GLP-1RAs are synthetic protein preparations that have partial or complete amino acid sequence homology with GLP-1 found in the body, are not easily degraded, have longer half-lives and have stronger biological activity. They can play the role of GLP-1. 49 GLP-1RA is primarily used for the treatment of T2DM 68 and works by mimicking the action of the naturally occurring hormone GLP-1, which is released by the intestines in response to food intake. GLP-1 helps regulate blood sugar levels by stimulating the release of insulin, suppressing glucagon secretion (which raises blood sugar levels), and slowing the rate at which the stomach empties, leading to a feeling of fullness and reduced appetite. 69 In addition to its use in diabetes management, GLP-1RA has also shown potential in other areas of research. Studies have explored its effects on weight loss, NAFLD, 70 and neurodegenerative diseases such as AD. 71 Furthermore, GLP-1RA has been investigated for its potential to reduce the risk of cardiovascular events in patients with or without diabetes. 5 , 19 Like any medication, GLP-1RAs may have side effects, including nausea, vomiting, diarrhea, and injection site reactions. These side effects are often mild and tend to improve over time. 72 , 73 , 74 Rare but serious side effects may include pancreatitis and allergic reactions. 75

Exenatide is a medication that belongs to the class of drugs known as GLP-1RAs. It is a synthetic version of the hormone exendin-4, which is found in the saliva of the Gila monster, a venomous lizard native to the southwestern United States. 76 Exenatide is composed of 39 amino acids and shares 53% sequence identity to human GLP-1. The second position of its N-terminus is glycine (alanine in GLP-1), which is not easily degraded by the DPP-4 enzyme. 77 Compared with GLP-1, the C-terminus of its amino acid sequence contains 9 additional amino acid residues (PSSGAPPPS), which are not easily degraded by peptide chain endonucleases; thus, it has a long half-life and strong biological activity. 78 The average half-life of exenatide is 2.4 h, 2 to 3 times per day. 78

Liraglutide

Liraglutide is a medication used to treat T2DM and obesity. 79 , 80 In the treatment of T2DM, liraglutide helps lower blood sugar levels by increasing insulin production and reducing glucose production by the liver. 81 It also slows stomach emptying, which helps control appetite and reduce food intake. 82 , 83 In addition to lowering blood sugar levels, liraglutide helps to reduce body weight by suppressing appetite and reducing energy intake, 84 , 85 but its associated costs and need for daily injections may limit its use in individuals with obesity. 86 , 87 , 88 Liraglutide was first approved by the FDA in 2010 under the brand name Victoza for the treatment of T2DM. 83 , 89 , 90 , 91 , 92 Since then, it has also been approved for other indications, such as chronic weight management, under the brand name Saxenda. 62 Liraglutide has an arginine at position 34 (GLP-1(7-37)) that is lysine, and its lysine at position 26 connects to a 16-carbon palmitic acid side chain linked by glutamic acid. Liraglutide shares 97% sequence homology with human GLP-1 and can bind to and activate GLP-1R. 78 The elimination half-life of liraglutide is 13 h, and only one injection per day is required. 62

Lixisenatide

Lixisenatide was developed by Sanofi to treat T2DM. 64 , 93 Structurally, lixisenatide is based on the exenatide structure but lacks proline at position 38, and six lysines are linked after serine at position 39. 94 The six lysine residues increase the rigidity of the molecule’s structure, thus allowing its drug properties to be improved. 78 These changes stabilize its structure, prevent protein degradation of the molecule in the circulation, and increase the circulation time enough to ensure once-daily injection (compared with exenatide, which is injected two or three times daily). The average half-life of lixisenatide is approximately 3–4 h. 95 Lixisenatide is a short-acting GLP-1RA agent, 96 , 97 and once-daily lixisenatide can improve patient compliance to a certain extent and reduce the occurrence of hypoglycemia. 98 , 99 , 100 The injection is usually given within one hour before the first meal of the day, preferably at the same time each day. It is important to avoid injecting lixisenatide after a meal or in case of a missed meal. The initial recommended dosage of lixisenatide is 10 mcg once daily for at least 14 days. After the initial period, its dosage may be increased to 20 mcg once daily if additional glycemic control is needed. The maximum recommended dosage is 20 mcg once daily. 101

Albiglutide

Albiglutide was approved by the FDA in 2014. As a GLP-1RA, 102 albiglutide works by stimulating insulin release and reducing glucagon production, leading to improved blood sugar control in patients with T2DM. 102 , 103 Albiglutide is a long-acting GLP-1RA injected subcutaneously once a week. The half-life of albiglutide is approximately 4 to 7 days. 102 Compared with the structure of human GLP-1(7-36), the amino acid sequence of albiglutide contains an arginine at position 8 (in GLP-1, this residue is lysine), and two modified GLP-1 peptide chains are fused to human serum albumin (HSA), thereby greatly extending its half-life. 104 , 105 Albiglutide is typically prescribed in combination with diet and exercise. The dosage of albiglutide is usually 30 mg once a week. It is administered as a subcutaneous injection (just under the skin). The injection site can be the thigh, abdomen, or upper arm. 102

The FDA set several usage restrictions upon the initial approval of Tanzeum (albiglutide), reflecting considerations of suitability and safety for specific patient groups. Firstly, Tanzeum is not recommended as a first-line treatment for patients inadequately controlled with diet and exercise. 49 Secondly, its safety and efficacy remain unclear in patients with a history of pancreatitis as it has not been studied in this group. 106 Additionally, Tanzeum is not suitable for treating type 1 diabetes or diabetic ketoacidosis, related to its pharmacological action and target disease. It is also not recommended for patients with existing gastrointestinal disease to avoid potential side effects or exacerbating the condition. 107 Further, serious risks associated with Tanzeum use include pancreatitis, acute kidney injury, renal impairment, and pneumonia, further limiting its use in specific conditions or susceptible patients. These restrictions and warnings demonstrate the FDA’s stringent consideration of patient safety in the drug approval process. 108 In March 2015, the FDA required a black box warning on Tanzeum due to the observed risk of thyroid C-cell tumors in animals, although it is unclear if this effect also occurs in humans. 108 Later, the FDA added a warning about the risk of anaphylactic shock to the medication’s label. This reaction is severe and potentially life-threatening, including symptoms like unease, tingling, dizziness, itching, hives, swelling, difficulty breathing, and fainting. 81 , 107 , 109

Tanzeum was discontinued by GlaxoSmithKline (GSK) in 2017, primarily due to economic factors. 110 , 111 Despite GSK’s attempts to gain a competitive edge through low pricing, Tanzeum failed to achieve sufficient market acceptance. 106 In 2017, Tanzeum was removed from the preferred drug list of leading pharmacy benefit manager (PBM) company Express Scripts and was replaced by Eli Lilly’s Trulicity, highlighting Tanzeum’s weak market presence. 106 , 108 Moreover, this decision was part of a broad strategic reform led by GSK’s new CEO Emma Walmsley. 106 This reform aimed to refocus the company’s efforts on areas with higher revenue potential, such as respiratory and HIV treatments, as well as oncology and immunology. 108 Additionally, Tanzeum struggled to establish a significant market share in the competitive GLP-1RA market, which was another reason GSK decided to withdraw the drug globally. 108

Dulaglutide

Dulaglutide was approved by the FDA in 2014 for the treatment of T2DM. 112 Dulaglutide is a once-weekly long-acting GLP-1RA. Compared with the structure of human GLP-1(7-37), the amino acid sequence of dulaglutide contains glycine at position 8, glutamic acid at position 22, and glycine at position 36. 113 It was then fused to the constant region (Fc) of modified human immunoglobulin G4 (IgG4) via a “-(Gly-Gly-Gly-Gly-Ser) 3-Ala-“ bridge and exhibits an average biological half-life of 90 h. 105 Dulaglutide is the first large-molecule GLP-1RA, and the weekly dosing frequency of dulaglutide can greatly improve patient compliance. 33 , 78 , 104 , 114

Semaglutide

Semaglutide is a long-acting GLP-1RA agent used once weekly to improve glycemic control in patients with T2DM. 115 Compared with the structure of human GLP-1(7-37), the amino acid sequence of semaglutide contains diaminoisobutyric acid at position 8, arginine at position 34, and acylated lysine at position 26. 31 Semaglutide has a longer aliphatic chain and increased hydrophobicity, but its hydrophilicity is greatly enhanced by PEG modification of the short chain. Modified DPP-4 can not only mask the enzymatic hydrolysis site of DPP-4 but also bind closely with albumin to reduce renal excretion and prolong the half-life. 35 , 104 , 116 On August 22, 2022, Novo Nordisk announced the primary results of the Phase II clinical trial for the dual-action compound CagriSema, which demonstrated effective blood sugar reduction and weight loss. CagriSema is composed of the GLP-1 RA semaglutide and the long-acting insulin analog cagrilintide, and can be administered subcutaneously once a week. 117

Beinaglutide

Beinaglutide was the first original drug approved for the treatment of obesity in China and the third GLP-1 class reduction drug approved worldwide, and it represents a new treatment option for overweight and obese patients. 67 , 118 , 119 Beinaglutide, a recombinant human GLP-1 (rhGLP-1) polypeptide, exhibits a remarkable resemblance to human GLP-1(7-36), with nearly 100% homology. 120 This innovative compound demonstrates dose-dependent efficacy in regulating glycemic control, suppressing appetite, delaying gastric emptying, and facilitating weight reduction. 121 Consequently, beinaglutide holds significant promise for advancing research in the areas of overweight/obesity and nonalcoholic steatohepatitis (NASH). 67 , 122 Beinaglutide is a natural human GLP-1(7-36)-NH2 expressed in Escherichia coli. This product was approved for the treatment of T2DM; it has a half-life of 11 minutes and requires 3 injections per day. 78

Polyethylene glycol liraglutide

Polyethylene glycol liraglutide (PEG-loxenatide) is a long-acting GLP-1RA. It was the world’s first PEGylated long-acting GLP-1RA. 123 PEG-loxenatide is used for blood glucose control in adult patients with T2DM. Structurally, the product was optimized on the basis of exenatide, and the glycine 2, methionine 14 and asparagine 28 positions were modified to improve enzyme stability and chemical stability based on the polypeptide backbone. Moreover, the C-terminal serine of the peptide was replaced by cysteine via site-directed mutagenesis performed with polyethylene glycol. 78 The half-life of PEG-loxenatide is approximately 1 week. 123

Multi agonists

In recent years, the development of dual and triple agonists related to GLP-1 has been vigorously pursued. 124 , 125 , 126 The design concept of these multi-agonists is to simultaneously regulate multiple key metabolic pathways to achieve more effective control over blood sugar, body weight, and overall metabolic health. 43 Currently, these drugs are primarily in the development and clinical trial stages, but preliminary research results have shown their potential powerful effects in reducing blood sugar and body weight. 127 , 128

Dual agonists

Dual agonists target both the GLP-1R and another specific receptor. 124 , 129 A common combination is GLP-1 with GIP or insulin-like growth factor. 130 For example, a popular dual agonist, tirzepatide (brand name Mounjaro), activates both GLP-1 and GIPR. 124 GLP-1, by activating its receptor, increases insulin secretion and reduces glucagon secretion, thereby lowering blood sugar levels. 131 , 132 , 133 Additionally, GLP-1 helps to delay gastric emptying and suppress appetite, aiding in weight management. 121 , 134 GIP, another insulin secretion agonist, helps release insulin, particularly after eating, enhancing the effects of GLP-1 and thereby improving the overall therapeutic efficacy of the drug. 125 , 130 In 2022, tirzepatide was approved by the FDA for the treatment of T2DM in the United States. 135 , 136 It is considered a significant breakthrough in diabetes treatment and is also being studied for the treatment of obesity due to its significant weight loss effects. 135 Tirzepatide is developed by Eli Lilly and has proven to provide superior blood sugar control and significant weight loss, making it particularly valuable in the treatment of T2DM. 136 , 137 , 138 Research and clinical trials have shown that tirzepatide not only improves blood sugar levels but also has a positive impact on cardiovascular risk factors. 139 , 140 , 141 Although dual agonists show advantages in efficacy, their safety and tolerability continue to be a focus of ongoing monitoring. 141 Common side effects include gastrointestinal reactions, such as nausea and vomiting, which are typically more common during the initial stages of treatment. 141 , 142 The Phase III clinical trials of tirzepatide were conducted in 77 research centers across seven countries, including the United States, Brazil, and Japan. 143 The trials recruited adult participants with T2DM and significantly reduced body weight and improved blood sugar control in these patients. 143 The safety profile of tirzepatide is similar to other drugs in its class, providing an effective new treatment option for patients with T2DM and obesity. Current dual agonists under investigation also include efinopegdutide and cotadutide. 144 , 145 , 146 , 147

Triple agonist

Triple agonists go even further. 148 These drugs act by simultaneously targeting three different agonists GLP-1R, the GIPR, and the GCGR. 149 , 150 , 151 These receptors each have independent yet complementary roles in the treatment of diabetes and obesity. 150 , 152 , 153 Activation of the GLP-1R can enhance insulin secretion, reduce glucagon secretion, delay gastric emptying, 154 and suppress appetite. 155 , 156 GIPR activation also promotes insulin release, especially after meals, helping to improve glucose utilization. 157 , 158 Activation of the insulin or Insulin-like Growth Factor 1 (IGF-1) receptor can enhance insulin sensitivity, improve glucose absorption and utilization by cells, and potentially have positive effects on cardiovascular health and long-term energy balance. 159 As of now, GLP-1-related triple agonists are primarily still in the development stage and have not been widely approved for use. 159 These drugs are not yet widely available on the market but have shown some potential in clinical trials. 160 , 161 For example, HM15211, a triple agonist developed by Hanmi Pharmaceutical in South Korea that activates GLP-1R, GIPR and GCGR has entered early clinical trials for the treatment of obesity and non-alcoholic steatohepatitis (NASH). 162 , 163 Retatrutide (LY-3437943), a novel triple agonist developed by Eli Lilly that targets GLP-1R, GIPR and GCGR, has shown potential in preliminary clinical data for providing excellent blood sugar control and significant weight reduction. 158 , 161 , 164 , 165 However, activating multiple receptors may lead to more complex side effects, and in some experiments, dual and triple agonists have indeed shown more severe side effects. 165 , 166 Retatrutide has now entered Phase III clinical trials. 161 The results of the Phase II clinical trials of retatrutide were published in The Lancet in 2023. 161 The trials involved adult participants with T2DM aged 18 to 75, conducted across 42 research and medical centers in the United States. 161 Over a period of 24 weeks, all dosage groups of retatrutide showed significant improvements in reducing glycated hemoglobin (HbA1c) and body weight compared to the placebo group, especially in the higher dosage groups. In terms of safety and tolerability, the adverse events were primarily mild to moderate gastrointestinal reactions, with no reports of severe hypoglycemia or death. 161

In summary, dual and triple agonists related to GLP-1 represent significant advances in the field of diabetes treatment, 167 , 168 demonstrating the future trend of enhancing therapeutic effects by targeting multiple biomarkers. 136 , 169 , 170 With the accumulation of more clinical data and the development of new drugs, these treatment options are expected to provide more effective and comprehensive treatment choices for diabetes patients. 161 , 167

Small molecule GLP-1RAs

Currently, most GLP-1RAs are based on proteins or peptides, meaning they are large molecules typically administered via injection. 37 Small molecule GLP-1RAs are chemically synthesized, and compared to protein-based drugs, they generally have smaller molecular sizes. 171 The development of small molecule GLP-1RAs aims to overcome some of the limitations of traditional protein or peptide-based GLP-1RAs, such as the need for injection. Small molecule drugs may offer the possibility of oral administration, which is more convenient and acceptable for patients. 171 Additionally, small molecule drugs may have better tissue permeability, longer half-lives in the body, and lower production costs. As of now, research on small molecule GLP-1RAs is still mainly in the laboratory and early clinical trial stages. 172 The challenges in developing these drugs include ensuring that they can effectively mimic the biological activity of large molecule GLP-1RAs while maintaining efficacy and selectivity. This review article will introduce some of the small molecule drugs that are currently receiving significant attention:

Orforglipron

Orforglipron is an oral small molecule GLP-1RA developed jointly by Eli Lilly and Chia Tai Tianqing Pharmaceutical Group. 173 Its research findings were recently presented orally at the 83rd Scientific Sessions of the American Diabetes Association and published in the New England Journal of Medicine. In a 26-week study, orforglipron demonstrated a significant dose-dependent effect on weight loss, with weight reduction ranging from 8.6% to 12.6% across various dosages, compared to only 2.0% in the placebo group. By week 36, this weight loss effect was even more pronounced, increasing from 9.4% to 14.7%, while the placebo group saw a reduction of only 2.3%. Additionally, in another Phase II study targeting patients with T2DM, orforglipron also showed significant effects in reducing A1C and weight, achieving the study’s primary and secondary endpoints. In this study, participants taking orforglipron experienced an average A1C reduction of 2.1% and an average weight loss of 10.1 kilograms at 26 weeks, which was significantly greater than those in the placebo and dulaglutide groups. Between 65% and 96% of participants taking orforglipron achieved an A1C level below 7.0% at 26 weeks. 174 Currently, Eli Lilly has initiated a Phase III development program to further investigate the efficacy and safety of orforglipron in treating obesity, overweight, and T2DM.

Danuglipron

Danuglipron is an oral GLP-1RA developed by Pfizer. In May 2023, Pfizer released the results of a Phase 2b clinical trial of the drug. The study involved 411 adult patients with T2DM and was designed as a randomized, double-blind, placebo-controlled trial where patients received varying doses of danuglipron or a placebo. The results showed that during the 16-week treatment period, patients who received the highest dosage (120 mg twice daily) of danuglipron experienced an average reduction in HbA1c of 1.16 percentage points and a weight loss of 4.17 kilograms. All dosages of danuglipron significantly reduced patients’ HbA1c and fasting blood glucose levels, with more pronounced weight loss effects observed in the 80 mg and 120 mg doses compared to the placebo group. Common adverse reactions included nausea, diarrhea, and vomiting. 172

GSBR-1290 is an oral small molecule GLP-1RA developed by Structure Therapeutics, aimed at treating T2DM and obesity. On December 18, 2023, Structure Therapeutics published the latest clinical data for GSBR-1290 on its official website. 175 Currently, GSBR-1290 is undergoing a 12-week Phase 2a randomized, double-blind, placebo-controlled clinical trial to assess its effectiveness in treating patients with T2DM and obesity. To date, the trial has enrolled 94 participants, with 54 in the T2DM group and 40 in the obesity group. Regarding safety, the majority of reported adverse events were mild to moderate, ranging from 88% to 96%, depending on the specific study group. Among the 60 participants treated with GSBR-1290, only one (2.8%, from the T2DM group) discontinued the study due to drug-related adverse events (AEs). As for clinical outcomes, in the T2DM group, there was a significant reduction in HbA1c (decreased by 1.01% to 1.02%, placebo-adjusted) and a clinically meaningful decrease in body weight of 3.26% to 3.51% after 12 weeks of treatment. In the obesity group, there was a significant and clinically meaningful reduction in body weight of 4.74% at week 8, with weight continuously decreasing during the 8-week treatment period. 175

Classical pathophysiological mechanisms of GLP-1

Glp-1 signaling pathway.

GLP-1 initiates signaling by binding to its receptor, GLP-1R, which is a G-protein-coupled receptor. 176 , 177 When GLP-1 binds to GLP-1R, it triggers the activation of G-proteins, leading to an increase in the intracellular second messenger cAMP. 34 , 39 , 177 The rise in cAMP activates protein kinase A (PKA), which then promotes the synthesis and secretion of insulin and inhibits the release of glucagon. 178 , 179 Additionally, cAMP can activate Rap1 through EPAC (Exchange Protein directly Activated by cAMP), 180 , 181 , 182 which is involved in regulating insulin secretion. 180 , 181 , 183 GLP-1 also activates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is crucial for maintaining the survival and function of pancreatic β-cells. 184 , 185 , 186 , 187

Interactions with other pathways

GLP-1 not only promotes the release of insulin but also enhances the response of pancreatic β-cells to insulin through the PI3K/Akt pathway, thereby improving insulin signal transduction and increasing the sensitivity of peripheral tissues to insulin. 1 , 188 GLP-1 reduces hepatic glucose production, partly by inhibiting the expression and activity of key gluconeogenic enzymes. 189 , 190 , 191 Activation of GLP-1R leads to the production of cAMP (cyclic Adenosine Monophosphate), which is achieved by activating Adenylyl Cyclase (AC). 191 , 192 Following the activation of GLP-1R, the βγ subunits of GPCRs can directly activate Class I PI3Ks. 1 These PI3Ks typically include the PI3Kα and PI3Kβ isoforms, which are composed of regulatory subunits containing SH2 domains and catalytic subunits. 193 These subunits can directly interact with the activated GPCR or do so via intermediary proteins such as insulin receptor substrate. 194 , 195 The activated PI3K catalyzes the conversion of membrane phospholipid Phosphatidylinositol-4,5-bisphosphate (PIP2) into Phosphatidylinositol-3,4,5-trisphosphate (PIP3). 196 The generation of PIP3 is a crucial step for the activation of Akt, as PIP3 provides a membrane docking site for Akt, facilitating its translocation to the cell membrane. 197 Akt, also known as Protein Kinase B (PKB), once positioned at the membrane, can be phosphorylated by PIP3-dependent kinase 1 (PDK1) and possibly PDK2 (such as mTORC2). 196 , 197 , 198 The phosphorylation of Akt is necessary for its full activation, allowing it to regulate a variety of downstream effector proteins involved in cell survival, proliferation, metabolism, and glucose transport. 199 Activated Akt promotes the expression and translocation of GLUT4 (Glucose Transporter Type 4) to the cell membrane, increasing cellular glucose uptake. 200 , 201 , 202 Simultaneously, Akt promotes cell survival by phosphorylating and inhibiting a series of pro-apoptotic proteins, such as Bad and the FOXO family. 202 , 203 , 204 Moreover, Akt can activate mTORC1, further promoting cell growth and protein synthesis. Through these molecular mechanisms, GLP-1 not only plays a crucial role in the treatment of diabetes by enhancing the function and protecting pancreatic β-cells from apoptosis, but it may also offer potential therapeutic benefits in fields such as cardiovascular and neural protection. 198 , 205 , 206 GLP-1 can also enhance the uptake and utilization of glucose in muscle and adipose tissues. 207 , 208 , 209 And GLP-1’s action in the brain reduces appetite and may influence energy expenditure. 176 , 210 , 211 These effects involve interactions with other satiety and hunger signals, such as PYY, CCK, insulin, and leptin. 212 , 213

The pathophysiological mechanism of GLP-1 in metabolic diseases

GLP-1 plays a crucial role in the pathophysiology of metabolic diseases, particularly in T2DM and obesity. 213 , 214 , 215

Role of GLP-1 in T2DM

GLP-1 significantly influences the functionality of pancreatic β-cells and α-cells, contributing to its therapeutic effect on T2DM. 132 , 216 , 217 As a vital incretin hormone, GLP-1 enhances glucose-dependent insulin secretion. 3 It also promotes proliferation and reduces apoptosis of pancreatic β-cells, thereby maintaining their quality and functionality. 130 , 218 At the molecular level, GLP-1 activates the cAMP response element-binding protein (CREB) via its receptor (GLP-1R), a transcription factor crucial for expressing the insulin gene. 3 , 130 , 219 GLP-1 also activates PKA and EPAC through a cAMP-dependent pathway. 1 , 220 PKA, a key enzyme, phosphorylates various target proteins, affecting their activity and function, which in turn promotes insulin synthesis and secretion. 178 , 180 The PI3K/Akt signaling pathway, activated by GLP-1, plays a vital role in maintaining pancreatic β-cell survival and promoting their proliferation. 221 , 222 Activation of Akt stimulates β-cell proliferation, reduces apoptosis, and enhances insulin secretion by regulating downstream effector molecules like Forkhead box protein O1 (FoxO1) and the glucose transporter type 2 (GLUT2). 223 , 224

GLP-1 also inhibits glucagon release from α-cells, which is beneficial for reducing blood glucose levels since glucagon promotes hepatic gluconeogenesis. 131 , 225 GLP-1’s action on α-cells regulates glucagon release. 131 The direct impact of GLP-1 on these cells slows the secretion of glucagon, essential for maintaining glucose stability, especially postprandially. 131 , 226 When GLP-1 binds to its receptor on α-cells, it activates intracellular cAMP production. 227 In α-cells, increased cAMP affects glucagon synthesis and release. 228 PKA, activated by cAMP, can regulate the activity of K-ATP channels in α-cells. 228 , 229 The opening of these channels is controlled by the intracellular ATP/ADP ratio. 229 Specifically, PKA modifies the open state of K-ATP channels through phosphorylation, affecting the cell membrane’s potential and intracellular calcium ion concentration. 230 , 231 By modulating the activity of K-ATP channels, GLP-1 indirectly controls the calcium signaling in α-cells, thereby influencing glucagon secretion. 232 , 233 GLP-1 inhibits the release of glucagon from α-cells through multiple mechanisms. GLP-1 can directly bind to the receptors on the surface of α-cells in the pancreas, inhibiting the secretion of glucagon from these cells. 234 , 235 Glucagon is a hormone secreted by pancreatic α-cells that stimulates the liver to release glucose. Therefore, inhibiting the release of glucagon is crucial when blood glucose levels need to be lowered. GLP-1 can stimulate pancreatic β-cells to release insulin. 236 , 237 Insulin not only directly lowers blood glucose levels but also further inhibits glucagon secretion from α-cells through a feedback mechanism. 238 The high concentration of insulin in the local pancreatic environment creates a negative feedback effect, reducing the amount of glucagon secreted by α-cells. 234 Additionally, GLP-1 can reduce blood glucose production by delaying gastric emptying and decreasing appetite, which also contributes to overall blood glucose control. 239 , 240 In summary, GLP-1 lowers blood glucose levels and inhibits glucagon secretion through direct action on α-cells, promotion of insulin secretion, and regulation of gastrointestinal activity. 241

GLP-1R is expressed not only on β-cells and α-cells but also on δ-cells in the pancreatic islets. 242 δ-cells primarily secrete somatostatin, which is an important regulatory hormone. 242 The expression of GLP-1R on δ-cells helps to inhibit the secretion of glucagon. 242 When GLP-1 binds to GLP-1R on δ-cells, it activates these cells and promotes the secretion of somatostatin. 243 Somatostatin is a potent inhibitory hormone that affects the surrounding α-cells and β-cells. It acts directly on neighboring α-cells to inhibit the secretion of glucagon and can also indirectly influence α-cells by inhibiting the secretion of other hormones. 243 In the local islet environment, a high concentration of somatostatin creates an inhibitory milieu, further reducing the activity of α-cells and the secretion of glucagon. 244 Additionally, somatostatin can inhibit gastrointestinal activity, reducing the secretion of pancreatic enzymes and gastric acid, thereby indirectly decreasing the demand for glucagon. 245 , 246 Hence, GLP-1 activates δ-cells and promotes somatostatin secretion, forming a multi-layered inhibitory mechanism that effectively reduces glucagon secretion.

The relative expression levels of GLP-1R on α-cells and δ-cells exhibit certain differences. These variations significantly influence the role of GLP-1 in regulating islet function and glucose homeostasis. 131 Research indicates that the expression level of GLP-1R on α-cells is relatively low. 131 Although GLP-1Rs are present, they are limited in number, making the direct inhibitory effect of GLP-1 on α-cells relatively weak. 247 The primary action often occurs through indirect mechanisms, such as insulin and somatostatin. 244 Conversely, the expression level of GLP-1R on δ-cells is relatively high. 248 GLP-1 can effectively bind to receptors on δ-cells, stimulating the secretion of somatostatin. 248 As a broad-spectrum inhibitory hormone, somatostatin can effectively inhibit glucagon secretion from α-cells and insulin secretion from β-cells. 249 , 250 Relevant studies suggest that the expression of GLP-1R on δ-cells is crucial for GLP-1’s regulation of somatostatin secretion and the overall inhibitory effect on glucagon. 248 , 251 , 252 This mechanism is particularly evident in the use of GLP-1-based drugs, such as GLP-1RAs, in the treatment of T2DM. In summary, the relatively higher expression of GLP-1R on δ-cells allows GLP-1 to indirectly inhibit glucagon secretion by promoting somatostatin secretion. In contrast, the lower expression of GLP-1R on α-cells results in a limited direct effect. Although these three types of cells each have distinct functions, it is more important to note that the somatostatin, glucagon, and insulin they secrete work together through mutual regulation and feedback mechanisms to maintain blood glucose balance and overall metabolic homeostasis. 253 , 254

GLP-1 usually refers to GLP-1(7-36), a peptide chain consisting of 36 amino acids and the primary active molecule. 255 GLP-1(7-36) stimulates the release of paracrine glucagon inhibitory factors by activating GLP-1R on β-cells and δ-cells. 241 DPP-4 cleaves GLP-1(7-36) at the 8th position, generating GLP-1(9–36). GLP-1(9–36) is the product of GLP-1(7-36) degradation by DPP-4, and this process rapidly reduces the activity of GLP-1(7-36). 35 , 256 , 257 Traditionally, GLP-1(9–36) was considered a metabolically inactive product of GLP-1, losing its primary function of regulating blood sugar. 258 However, increasing research suggests that GLP-1(9–36) may have other physiological roles. Recent studies show that GLP-1(9–36) can activate the inhibitory G protein (Gi/o), leading to the translocation of secretory granules (SG) beneath the cell membrane, thereby inhibiting glucagon secretion. 241 This mechanism is unaffected by genetic or pharmaceutical inhibition of GLP-1R, but it is sensitive to pertussis toxin. As exendin-4 is more resistant to DPP-4-induced degradation, this mechanism is not activated by exendin-4. 241 GLP-1(9–36) can directly act on pancreatic α-cells to inhibit the secretion of glucagon. Recent studies have shown that GLP-1(9–36) is particularly effective at low glucose concentrations, with its inhibitory effect being similar to that of GLP-1(7-36). 241 GLP-1(9–36) retains its ability to inhibit glucagon secretion even after GLP-1R inactivation, suggesting that its mechanism of action may not be entirely dependent on the GLP-1R. 241 GLP-1(9–36) promotes the undocking of secretory granules (SG) by inhibiting the entry of Ca 2+ through voltage-gated Ca 2+ channels. As a result, GLP-1(9–36) reduces the number of granules available for exocytosis in α-cells, thereby decreasing the release of glucagon. 241 This mechanism decreases intracellular Ca 2+ concentration, thereby inhibiting glucagon secretion. 241 Additionally, GLP-1(9–36) can effectively inhibit glucagon secretion induced by β-adrenergic stimulation, amino acids, and membrane depolarization, indicating its inhibitory effect under various stimulatory conditions. 241 In α-cells of patients with T2DM, the ability of GLP-1(9–36) to inhibit glucagon secretion is lost. This may be due to altered α-cell function in diabetic patients, which impairs the efficacy of GLP-1(9–36). 241 In vivo experiments have shown that high concentrations of exogenous GLP-1(9–36) can lower circulating glucagon levels during insulin-induced hypoglycemia. However, this effect is significantly diminished or absent in diabetes. 241 As a degradation product of GLP-1(7-36), GLP-1(9–36) has a notable inhibitory effect on glucagon secretion, demonstrated in both in vitro and in vivo studies. However, this inhibitory effect is significantly weakened in patients with T2DM, indicating that its potential application in diabetes treatment requires further investigation. 241 Through this series of complex molecular and cellular mechanisms, GLP-1 plays a vital role in the physiological and pathological processes of metabolic diseases like T2DM. 232 , 233 , 241 , 259 (Fig. 2 ).

Mechanisms of Blood Glucose Reduction by GLP-1 in Pancreatic α, β, and δ Cells. This illustration demonstrates how GLP-1 reduces blood glucose levels by acting on different pancreatic cell types. In β cells, GLP-1(9–36) activates the GLP-1R, which increases cAMP levels, subsequently activating PKA and CREB, leading to the promotion of insulin secretion. The PI3K/Akt pathway enhances glucose sensitivity in β cells, promoting insulin secretion. This pathway also supports β cell survival and proliferation, ensuring an adequate β cell mass to maintain normal insulin secretion. This signaling cascade results in increased insulin gene expression, enhanced protein synthesis, improved cell survival, and reduced apoptosis. Additional metabolic effects include fatty acid oxidation, gluconeogenesis, and energy expenditure. In α cells, GLP-1(7-36) mainly regulates function through indirect mechanisms. GLP-1R expression is lower in α cells compared to β and δ cells, resulting in relatively less direct action of GLP-1 on α cells. Through paracrine effects via β cells, GLP-1 enhances insulin secretion, which in turn inhibits glucagon secretion from α cells. Additionally, GLP-1 promotes somatostatin secretion from δ cells, which inhibits glucagon secretion from α cells. GLP-1(7-36) can suppress glucagon secretion in α cells by increasing cAMP levels, activating PKA and EPAC, leading to a decrease in intracellular calcium concentration and reduced glucagon release. GLP-1(9–36) inhibits glucagon secretion by activating inhibitory G proteins (Gi/o) and suppressing PKA activity through a GCGR-dependent mechanism. By promoting the undocking of secretory granules (SG), GLP-1(9–36) reduces the number of granules available for exocytosis, thereby decreasing the release of glucagon. δ cells primarily secrete somatostatin. GLP-1(7-36) regulates somatostatin secretion by modulating calcium channels and affecting membrane potential changes. The action of GLP-1(7-36) on δ cells may be more indirect, such as through the influence on hormones secreted by β and α cells (insulin and glucagon), which indirectly affects δ cell somatostatin secretion. Additionally, somatostatin can inhibit gastrointestinal activities, reducing the secretion of pancreatic enzymes and gastric acid, thereby indirectly lowering the demand for glucagon

Role of GLP-1 in obesity

GLP-1 reduces appetite and food intake through its actions in the CNS. 212 , 260 , 261 By interacting with receptors in the hypothalamus, GLP-1 influences satiety and reduces the consumption of food in both animals and humans. 262 It functions not only in peripheral tissues but also directly within the CNS, crossing the blood-brain barrier or being produced centrally to act on the brain. 262 , 263 GLP-1 regulates energy balance and food intake by acting on specific brain regions, especially the hypothalamus, a key area responsible for hunger and fullness sensations. 264 , 265 , 266 The hypothalamus contains various neurons that respond to different nutritional signals and hormones, like GLP-1, to regulate food intake. 265 , 266 When GLP-1 binds to its receptors in the hypothalamus, it activates specific neurons, including those that promote satiety (POMC/CART neurons) and inhibits those that induce hunger (NPY/AgRP neurons), thereby enhancing the feeling of fullness and reducing food intake. 233 , 267

GLP-1 can slow down gastric emptying through its effects on smooth muscles and the nervous system in the gastrointestinal tract. 264 , 268 Released at the gut’s end, GLP-1 acts on its receptors in the gastrointestinal tract, leading to reduced gastric muscle contractions and extended food retention in the stomach. 264 , 269 Furthermore, GLP-1 can slow down gastric emptying by activating the vagus nerve, a part of the autonomic nervous system crucial for regulating the activities of the gastrointestinal tract. 268 When activated, the vagus nerve can reduce the contraction of the stomach, thereby slowing down food emptying. 269 The prolonged retention of food in the stomach enhances the feeling of fullness, naturally reducing overall food intake. 270 , 271 Additionally, slower gastric emptying helps stabilize postprandial blood glucose levels. Reducing food intake and extending satiety are significant for weight management and loss. By regulating gastric emptying, GLP-1 not only aids in short-term appetite control but may also contribute positively to long-term energy balance and weight management. 176

GLP-1RAs and diseases

As a rising star in recent years, GLP-1RAs are not only effective in metabolic diseases but also play a role in non-metabolic disorders, affecting multiple systems including the musculoskeletal, nervous, cardiovascular, and digestive systems, and can even have implications in oncological diseases.

Musculoskeletal system

Disorders associated with the musculoskeletal system often cause painful swelling and permanent damage in the joints of the body, especially the hips, knees and thumbs. These diseases may affect more people in today’s aging society. Because of the close relationship between risk factors in human metabolism and the expression of GLP-1R in the musculoskeletal system, GLP-1RAs may have great potential in the treatment of many diseases of the musculoskeletal system. 15 , 272

GLP-1RAs and joint disorders

Glp-1ras in oa.

GLP-1R expression was detected via immunohistochemistry in articular chondrocytes from both normal and osteoarthritic individuals. 273 The primary outcome of GLP-1R expression involves suppressing the release of cytokines into the synovial fluid, leading to a reduction in inflammation. 274 , 275 This, in turn, diminishes additional downstream effects, including oxidative stress, the secretion of pro-degradative substances, modifications to cell phenotype (hypertrophy, M1/M2 macrophage phenotype, fibrosis), and damage or deterioration of joint cells (apoptosis, senescence). 15 , 276

The activation of GLP-1R is linked to decreased NF-κB pathway activity Treatment with GLP-1RAs can effectively mitigate chondrocyte apoptosis caused by endoplasmic reticulum stress and alleviate the associated inflammatory response. 277 , 278 , 279 , 280 This effect is accomplished through the inhibition of JNK, NF-κB, and other relevant signaling pathways. 273 Moreover, GLP-1RAs could decelerate the progression of OA and mitigate pathological damage in a rat OA model. 273 In addition, in a rat model of inflammatory OA induced by monoiodoacetic acid (MIA), researchers have shown that the activation of GLP-1R triggers the PKA/CREB signaling pathway, leading to a reduction in cartilage inflammation. 281

Inflammation in OA is closely related to the activation of macrophages. 282 , 283 These cells accumulate in the synovial membrane and subchondral bone, releasing pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, which promote the degradation of joint cartilage and the inflammatory response. 284 , 285 , 286 Macrophages express GLP-1Rs, which are involved in regulating their inflammatory responses. Binding of GLP-1 or GLP-1RAs to these receptors can activate the cAMP/PKA signaling pathway, affecting key transcription factors like NF-κB. 287 , 288

This binding initiates typical GPCR signaling, leading to G protein activation and increased intracellular cAMP. 289 The rise in cAMP activates PKA, a versatile protein kinase that phosphorylates various target proteins. 290 , 291 , 292 In macrophages, PKA regulates gene expression by phosphorylating transcription factors like CREB. 293 CREB activation can promote the expression of anti-inflammatory genes while inhibiting inflammatory genes. 294 , 295 In inflammation regulation, NF-κB is a key transcription factor. 296 , 297 , 298 Typically, NF-κB binds to its inhibitor IκB in the cytoplasm. 297 , 299 When IκB is phosphorylated and degraded, NF-κB can move to the nucleus, activating multiple inflammation-related genes. 300 , 301 This not only affects the intracellular signaling of macrophages but also their response to the external environment, including their effects on chondrocytes and other synovial cells. 302 , 303 , 304 , 305

GLP-1R signaling, through PKA, inhibits this process, possibly by promoting IκB stability or inhibiting its phosphorylation, thus reducing NF-κB activation and nuclear translocation. 8 , 281 Through these mechanisms, GLP-1R signaling influences the production of inflammatory factors in macrophages. 306 For example, the reduction in TNF-α, IL-1β, and IL-6 helps regulate local and systemic inflammatory responses. 307 , 308 Additionally, GLP-1R signaling may affect other macrophage functions, such as phagocytosis, migration, and cell survival. 281

By reducing macrophage-mediated inflammatory responses, GLP-1RAs have the potential to alleviate symptoms of OA, including pain and joint stiffness. 281 , 309 Moreover, reducing inflammation may slow down the degradation of joint cartilage, providing long-term joint protection. 310 , 311 GLP-1RAs also enhance autophagy, a process of cellular clearance of damaged and outdated components. 13 , 312 Regulation of autophagy may help remove harmful proteins and other cellular debris accumulated under inflammatory conditions, which is potentially important for maintaining the health of joint tissues. 313 , 314

In one study, OA was induced in rats by injecting MIA into the knee joint, mimicking the pathological changes of human OA. 315 Subsequently, rats were treated with liraglutide through subcutaneous injection to observe its therapeutic effect on OA. 315 The expression levels of GLP-1R, PKA/CREB signaling pathway components, and inflammation-related proteins (such as TNF-α, IL-1β, and IL-6) in the rat knee cartilage tissue were measured using Western blot and immunoprecipitation techniques. 315 The results showed that, in the OA rat model, liraglutide could activate the PKA/CREB signaling pathway and inhibit the inflammatory response through this pathway, thereby alleviating OA symptoms. 316 These findings provide scientific evidence for developing new OA treatment strategies, confirming the potential of GLP-1 agonists in treating OA. 315 , 316 , 317

GLP-1R is expressed in human monocyte-derived macrophages and the mouse macrophage cell line RAW264.7. 279 , 318 c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase (MAPK) involved in regulating cellular stress responses and inflammation. 318 Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor involved in cell growth, differentiation, and inflammatory responses. 319 , 320 , 321 Researchers found that activation of GLP-1R could play a key role in regulating macrophage polarization by adjusting the phosphorylation levels of JNK and STAT3. 318 , 322 Macrophages have two polarization states, M1 typically has pro-inflammatory properties, while M2 has anti-inflammatory properties. 323 , 324 , 325 Specifically, activation of GLP-1R leads to an increase in cAMP levels, which in turn activates PKA, a widely regulating enzyme of cellular functions, capable of phosphorylating a variety of target proteins, thereby initiating the PKA/CREB signaling pathway. 326 , 327 This not only prevents the phosphorylation of JNK but also promotes the phosphorylation of STAT3, aiding the shift of macrophages to an anti-inflammatory M2 phenotype. 327 In the inflammatory environment, the M1 to M2 shift promoted by GLP-1 is crucial for reducing the expression of inflammatory factors such as IL-6, TNF-α, and iNOS. 8 , 15 , 328

Chondrocytes are the only cell type in joint cartilage, responsible for synthesizing and maintaining the integrity of the cartilage matrix. 329 , 330 In degenerative joint diseases like OA, the metabolic balance of chondrocytes is disrupted, leading to the overproduction of degrading enzymes and inflammatory mediators, including iNOS, MMP-13, and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5), which participate in cartilage degradation and inflammatory processes. 331 iNOS (inducible nitric oxide synthase) produces nitric oxide (NO) during inflammation, modulating signal transduction; MMP-13 (matrix metalloproteinase-13) is involved in cartilage degradation; 331 ADAMTS5 is closely related to cartilage damage and inflammation. 332 , 333 , 334 The NO produced by iNOS, as a free radical, can regulate intracellular signal transduction and modulate the inflammatory response. 335 , 336 The expression of iNOS is primarily activated by the NF-κB pathway, which is activated and translocated to the nucleus upon inflammatory stimulation (such as bacterial endotoxins or pro-inflammatory cytokines), thus increasing the transcription and expression of iNOS. 337 , 338 , 339 GLP-1 can exert its anti-inflammatory effects by activating its receptor, GLP-1R. 339 When GLP-1 binds to GLP-1R, it activates the cAMP signaling pathway, leading to increased cAMP levels. 1 , 340 The rise in cAMP further activates PKA, which can inhibit the NF-κB signaling pathway, reducing the production of inflammatory factors such as iNOS and other inflammation-related proteins. 12 , 340 , 341 The expression of MMP-13 is regulated by IL-1β and TNF-α. These factors promote the transcription of the MMP-13 gene by activating the MAPK and NF-κB signaling pathways. 342 , 343 , 344 The GLP-1R signaling pathway may also affect the expression of MMP-13 and ADAMTS5, by reducing the signal transduction caused by IL-1β, thus decreasing their synthesis. 345 , 346 GLP-1 may also reduce the expression of cartilage-degrading enzymes by inhibiting the MAPK pathway or activating anti-inflammatory pathways such as PI3K/Akt, thereby alleviating cartilage damage. 206 , 347

In another study, treatment of primary mouse chondrocytes with liraglutide reduced the mRNA expression levels of iNOS, MMP-13, and ADAMTS5, leading to a decrease in the secretion of inflammatory markers, including NO, prostaglandin E, and IL-6. 348 Similarly, in human chondrocytes stimulated by TNF, GLP-1 analogs (such as liraglutide) showed an anti-catabolic effect, reducing the mRNA expression of MMP-3, MMP-13, and ADAMTS5. 349 , 350 At the same time, the levels of two important components of the cartilage matrix, proteoglycans (a large molecule and a major component of the cartilage matrix) and type II collagen (the main structural protein of cartilage), increased. 349 , 350 This change suggests that liraglutide not only inhibits inflammation and cartilage degradation but may also promote the synthesis and accumulation of cartilage matrix, thereby helping to protect and repair joint cartilage. 273 Furthermore, a study using the anterior cruciate ligament transection (ACLT) rat model further confirmed that subcutaneous injection of liraglutide at 50 μg/kg/day, whether for 3 weeks or 6 weeks, could reduce OARSI scores, highlighting the potential of liraglutide in treating joint degeneration. 273

GLP-1RAs and RA

The role of GLP-1RA was also investigated in RA, which is characterized by chronic inflammation of the synovium and joint destruction. In fibroblast-like RA synoviocytes, the administration of lixisenatide resulted in a reduction in the inflammatory response. 347 This was achieved by decreasing the expression of proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8). 15 , 351 , 352 Moreover, lixisenatide has been shown to inhibit matrix metalloproteinase (MMP) activity and effectively block various cell signaling pathways, including the JNK, activator protein-1, and NF-κB pathways. 353 These findings confirm that in the synovium, GLP-1R is expressed on two different cell types, macrophages and fibroblast-like synoviocytes, which are specialized cells distributed within the synovial intima and subintima, and these cell types play important roles in hyaluronic acid synthesis, metabolite processing, and clearance of matrix degradation fragments. 354

GLP-1RAs and musculoskeletal health

Glp-1ras and bone.

The quality of bone depends on bone metabolism, and the main factors affecting bone metabolism include osteoclasts, osteoblasts, and calcitonin. 355 , 356 , 357 According to most related studies, osteoclasts and osteoblasts are indispensable for bone remodeling, and bone resorption and bone formation are mediated by osteoclasts and osteoblasts, respectively. 358 GLP-1R is present in bone marrow stem cells (BMSCs), 15 , 359 osteoblasts, 15 osteocytes, 360 and osteoclasts, 361 and GLP-1RAs have the potential to impact these cells.

GLP-1RAs and osteoclasts The greater degree of bone degradation observed in mice lacking GLP-1R indicates that GLP-1R signaling suppresses osteoclast differentiation and bone resorption. 362 In an experimental study in which osteoclast formation and bone resorption were induced in mice through lipopolysaccharide (LPS) administration, researchers discovered that simultaneous treatment with exendin-4 resulted in a significant decrease in the number of osteoclasts, the proportion of bone resorption pits, and the levels of the bone resorption marker CTX compared to injection with LPS alone. 363 According to previous reports, exendin-4, a GLP-1RA, has the potential to inhibit LPS-induced osteoclast formation and bone resorption in vivo. 363 , 364 This inhibition is believed to occur through the suppression of LPS-induced TNF-α production in macrophages. 15 Studies have indicated that GLP-1R KO mice exhibit greater numbers of osteoclasts and greater bone resorption than wild-type controls. 364 Additionally, µCT analysis revealed that, compared with their wild-type counterparts, hyperlipidemic rats treated with subcutaneous GLP-1 for 3 days exhibited increased bone mass in the femur and vertebrae. 365

Diabetic patients have a higher risk of fractures than does the general population. 366 Mice with type 1 diabetes (T1D) exhibit a reduction in bone mineral density (BMD) and compromised microstructural integrity. 367 The administration of liraglutide also impeded osteoclastic bone formation, thereby inhibiting bone resorption and exerting protective effects on bone health in T1D mice. 367 Specifically, liraglutide, both alone and in combination with insulin, effectively suppressed the formation of osteoclasts. This effect is achieved by reducing the expression of Trem2 and NFATc1 and downregulating the expression of CTSK and TRAP to inhibit bone resorption activity. These findings provide further evidence for the impact of GLP-1RAs on osteoclastic bone resorption. 367 A study involving 12-week-old ovariectomized mice revealed that administering liraglutide for 4 weeks effectively prevented the loss of trabecular bone. The analysis of bone tissue morphology revealed that there were no alterations in the rate of bone formation or in the levels of calcitonin or sclerostin in these mice. These findings suggest that liraglutide specifically reduces bone resorption without influencing bone formation. 368

Since GLP-1R is expressed in thyroid C cells and GLP-1 directly stimulates the secretion of calcitonin, which is a potent inhibitor of bone resorption in osteoclasts, GLP-1 may contribute to the nutrient-mediated reduction in bone resorption. 369 , 370 Genetic disruption of GLP-1R signaling leads to cortical osteopenia and heightened bone fragility, primarily caused by increased bone resorption by osteoclasts. This change was accompanied by a decrease in thyroid calcitonin expression. Furthermore, the administration of exogenous GLP-1 resulted in elevated calcitonin expression in the thyroids of normal (wild-type) mice. 362 The administration of calcitonin successfully reduced the levels of urinary deoxypyridinoline in GLP-1R knockout mice. Additionally, treatment with GLP-1RA and exendin-4 increased the expression of the calcitonin gene in the thyroids of normal (wild-type) mice. These findings provide evidence that the regulatory influence of endogenous GLP-1R signaling on bone resorption is likely mediated through pathways that involve calcitonin. 362 Considering the expression of the GLP-1R in thyroid C cells and the ability of GLP-1 to stimulate calcitonin secretion through a cAMP-mediated mechanism in vitro, it is plausible that calcitonin plays a role in the alterations in bone metabolism observed in GLP-1R-treated animals. 369 , 370 Later, quantitative real-time PCR analysis demonstrated that the administration of exendin-4, a GLP-1RA, resulted in significant upregulation of thyroid calcitonin mRNA levels in wild-type mice. 362

GLP-1RAs and Osteoblasts Osteoblasts arise through the differentiation of mesenchymal stem cells and play a crucial role in the process of bone formation. Stimulating GLP-1R in BMSCs triggers the buildup of nuclear β-catenin, which, in turn, activates osteogenic genes by binding with TCF7L12. 371 In osteoblasts, the administration of GLP-1 and GIP incretins suppressed the excessive expression of the pro-degradative enzymes MMP-3 and MMP-13 induced by IL-1β stimulation. 372 In vitro, GLP-1 disrupts the ability of osteoblasts to survive and differentiate by triggering the activation of c-Fos, which is a proto-oncogene. 373 In fact, when BMSCs are exposed to exendin-4, the expression of genes related to bone development factors such as Runx and Osterix, as well as genes responsible for producing the bone matrix such as Balp and Bglap, is upregulated. Moreover, stimulation of GLP-1R in BMSCs results in the accumulation of β-catenin in the cell nucleus. This accumulation facilitates the binding of β-catenin to TCF7L12, triggering the activation of genes associated with osteogenesis. 371

In a study examining the effects of GLP-1RA on osteoporosis induced by ovariectomy in aged rats, administering exendin-4 for 16 weeks prevented deterioration of the trabecular microarchitecture and increased bone strength. This was achieved by inhibiting bone resorption through an increase in the OPG/RANKL ratio and promoting bone formation by enhancing the expression of osteoblast-specific transcription factors. 374 Exendin-4 has also been shown to stimulate osteoblast activity and mitigate bone loss in an ovariectomized mouse model. 374 Liraglutide can directly enhance bone formation in the MC3T3-E1 osteoblastic cell line. This effect is achieved through the activation of signaling pathways such as the ERK1/2, PI3K/AKT, and cAMP/PKA/β-cat-Ser675 pathways, which are mediated by GLP-1RAs. 375 (Fig. 3 ).

The Effects of GLP-1RAs on osteoclasts and osteoblasts. GLP-1RAs aid in weight loss by regulating the gut-brain axis and interacting with leptin, while weight loss can alleviate the harmful effects of obesity on the body, particularly in knee OA, by reducing joint loading and inflammation. Obesity disrupts bone metabolism and leads to increased bone resorption, but GLP-1RAs can inhibit this damage and improve bone health by increasing the OPG/RANKL ratio, reducing osteoclast activity, and promoting bone formation

GLP-1RAs and muscle

GLP-1RAs and Muscle Atrophy In previous experiments, exendin-4 (Ex-4) inhibited the expression of myostatin (MSTN), atrophy-factor F-box only protein 32 (atrogin-1) and muscle ring finger protein 1 (MuRF-1) in dexamethasone-treated C2C12 myotubes. 376 , 377 , 378 In a dexamethasone-induced muscle atrophy model, Ex-4 ameliorated muscle atrophy by inhibiting muscle atrophy factor and enhancing myogenic factors (MyoG and MyoD), thereby increasing muscle mass and function. In the muscle atrophy mouse model, Ex-4 also increased muscle mass and muscle fiber size and improved muscle function. In addition, treatment with the long-acting GLP-1RA duraglutide restored muscle mass and function in DBA/2J-mdx mice. 379

GLP-1RAs, particularly PF1801, have demonstrated effective relief in inflammatory myopathies, such as polymyositis (PM), through preclinical studies. 376 , 380 The therapeutic effects of PF1801 are primarily achieved by modulating several key proteins that play central roles in inflammation and cellular metabolism. 380 Firstly, the expression of GLP-1R is enhanced in the inflamed muscle fibers under pathological conditions, revealing the critical role of GLP-1R in regulating the muscle’s response to inflammation. 381 PF1801 activates these receptors, initiating a series of biological responses that influence the inflammatory state of muscle cells, thereby alleviating inflammation. Next, PF1801 exerts its effects by activating AMP-activated protein kinase (AMPK). 382 As a central node in energy sensing and metabolic regulation, the activation of AMPK helps maintain cellular energy balance and prevents cell death due to energy depletion. 383 , 384 Importantly, the activation of AMPK reduces the expression of phosphoglycerate mutase 5 (PGAM5), which plays a promotive role in cell necrosis by contributing to mitochondrial dysfunction and the production of reactive oxygen species (ROS). 385 , 386 , 387 Thus, by inhibiting PGAM5, AMPK suppresses necrosis, reduces ROS accumulation, and mitigates oxidative stress. 385 , 387 PF1801 displays its anti-inflammatory effects by lowering levels of inflammatory mediators such as TNFα, IL-6, and HMGB1, and enhances the cell’s antioxidant capability by upregulating molecules like Nfe2l2, Hmox1, Gclm, and Nqo1, which further improves cellular defense against oxidative stress and protects them from further damage. 382 Through this sophisticated molecular regulation, PF1801 not only alleviates inflammation and necrosis in muscle fibers but also enhances the energy and antioxidant status of muscle cells. 382 This contributes to maintaining muscle strength and reducing inflammation. This comprehensive change reflects how alterations in the expression of individual key proteins can impact the entire metabolic and inflammatory pathways, thereby improving disease conditions and enhancing therapeutic efficacy. 376

GLP-1RAs in Enhancing Exercise Endurance Studies indicate that acute exercise and short-term endurance training significantly increase GLP-1 secretion in mice. In endurance-trained men, GLP-1 plasma concentrations are elevated immediately at 30 and 45 minutes after exercise. 388 To confirm the role of GLP-1 in enhancing physical endurance and the possible mechanisms involved, an in vivo AAV-mediated GLP-1 overexpression model and an in vitro siRNA-mediated AMPK knockdown model were generated. We demonstrated that GLP-1 enhances physical endurance by inducing skeletal muscle remodeling, which may be mediated by GLP-1R/AMPK signaling. 389 Overall, GLP-1 secretion is induced by exercise. Overexpression of GLP-1 in skeletal muscle can improve endurance. These results suggest that GLP-1 may improve exercise endurance in mice by enhancing skeletal muscle glycogen synthesis and glucose uptake. Mitochondrial content and function in skeletal muscle are regulated by GLP-1. 389 The interaction between GLP-1 and its receptor GLP-1R initiates the AMPK signaling cascade within skeletal muscle tissue. This initiation precipitates a multitude of alterations in the cellular milieu, notably the augmentation of mitochondrial biogenesis-a mechanism responsible for the genesis of new mitochondria. Furthermore, GLP-1 augments mitochondrial efficacy, as manifested by the ameliorated oxidative metabolism of muscle tissue. This enhancement is demonstrable through an increase in mitochondrial DNA content, the upregulation of genes integral to mitochondrial biogenesis, and the increased expression of proteins pivotal in oxidative phosphorylation. These cellular transformations contribute significantly to enhanced endurance during exercise, thereby underscoring the critical role that GLP-1 plays in the regulation of mitochondrial function and content in skeletal muscle. 389

GLP-1RAs and fat metabolism

GLP-1RAs work via numerous mechanisms that contribute to weight loss, one of the most well-known of which is the gut-brain axis. 212 , 213 , 390 Within this axis, GLP-1 functions by acting on both the gut and the brain. 391 Furthermore, the combination of GLP-1-mediated signaling and the adipocyte hormone leptin has recently garnered increased interest. Notably, leptin may serve as a crucial biological signal for GLP-1, working in synergy, to decrease food intake and body weight. The effects of the leptin-GLP-1 interaction may be governed by intracellular signaling pathways, including those involving phosphorylated STAT3 and PTP1B. 15 , 392

In Wistar rats, a diet high in fat was found to lead to a decrease in the ratio of OPG/RANKL, which resulted in increased bone resorption and ultimately a reduction in bone mass. The administration of GLP-1RA or exendin-4 to rats fed a high-fat diet resulted in an increase in the OPG/RANKL ratio and a reduction in the degree of bone loss. It was observed that the treatment of rats on a high-fat diet with exendin-4 resulted in a decrease in the number of osteoclasts and the area of eroded surfaces, while there was an increase in the osteoid area, bone mass, and trabecular bone volume. These effects were compared to those of untreated controls that were also maintained on a high-fat diet. 393 As a result, GLP-1RAs could mitigate the detrimental effects of hyperlipidemia-induced skeletal defects, leading to an improved prognosis in individuals with OA.

On the surface of the cartilage, there is a layer of special phospholipids. When a joint bears weight, it functions as a lubricant, playing a crucial role in enabling the joint to continue operating efficiently and smoothly. Altering the composition of this phospholipid layer can impact the functioning of the corresponding joint. For instance, changes in the composition of this phospholipid layer have been observed by researchers, along with their detrimental effects on the bones and joints of individuals with OA. 394 Surprisingly, GLP-1RAs can influence the phospholipid structure and cytokines surrounding joints, leading to beneficial transformations that safeguard joints and even facilitate partial repair of any existing damage. 395 (Fig. 4 ).

The Effects of GLP-1RAs on Musculoskeletal System. GLP-1RAs inhibit chondrocyte apoptosis, reduce inflammation, and protect articular chondrocytes in OA and RA through various mechanisms, including suppressing cytokine release, inhibiting the NF-κB pathway, and reducing inflammation-related gene expression. They have shown to reduce the inflammatory response by decreasing the expression of proinflammatory cytokines and inhibiting matrix metalloproteinase activity and cell signaling pathways. GLP-1R expression is found in macrophages and fibroblast-like synoviocytes, which are important for maintaining synovial fluid homeostasis. GLP-1R signaling stimulates calcitonin secretion, which inhibits bone resorption, and disruption of GLP-1R leads to increased bone resorption and decreased calcitonin expression. GLP-1RAs have pleiotropic effects on skeletal muscle, including inhibiting muscle atrophy, preserving muscle strength, and enhancing exercise endurance, through GLP-1R-mediated signaling pathways. GLP-1RAs can influence the composition of the phospholipid layer on cartilage, leading to beneficial effects on joint health and potentially facilitating repair of existing damage in individuals with OA

GLP-1RAs in nervous system

In the nervous system, GLP-1 can decrease oxidative stress and inflammatory responses, potentially through reducing the generation of ROS and decreasing the expression of inflammatory cytokines. Activation of its receptor by GLP-1 can promote the phosphorylation of CREB, subsequently fostering the expression of genes related to neuronal survival and regeneration. 396 , 397 , 398 , 399

GLP-1RAs and nerve cells

GLP-1 can modulate peripheral nerves through the ERK (extracellular signal-regulated kinase) signaling pathway, reducing the occurrence of neurological dysfunction. 400 Researchers have discovered that GLP-1RAs exhibit a noticeable increase in the level of phosphorylated ERK1/2 within the sciatic nerve of diabetic rats. This observation led them to speculate that GLP-1 analogs might possess distinct neurotrophic properties and exert protective effects specifically on the nerve. 71 , 395 , 401 , 402 , 403

Astrocytes, the most abundant cell type in adult brain nerve tissue, have recently been recognized for their pivotal role in regulating glucose and energy homeostasis. 404 , 405 , 406 These cells not only respond to signals from leptin and insulin but also adapt to alterations in brain metabolism to accommodate behavioral changes by controlling glucose transport. 406 , 407 Furthermore, astrocytes express GLP-1R, which has been found to be crucial for their proper functioning. 408 Studies have shown that the loss of GLP-1R in astrocytes can impair mitochondrial integrity, leading to the dysfunction and inhibition of glucose uptake and β-oxidation. 407 GLP-1 inhibits glucose uptake in astrocytes and promotes beta-oxidation, which is essential for regulating energy balance in the brain and maintaining mitochondrial integrity. 406 When GLP-1R is knocked out in astrocytes, it activates an integrated stress response, which affects the overall metabolic state by increasing the production of FGF21. 405 This suggests that signaling through GLP-1R in astrocytes is crucial for maintaining the metabolic stability and functionality of the cells. 406 FGF21 is recognized as a stress response factor that addresses mitochondrial dysfunction in cells. In astrocytes lacking GLP-1R, the increase in FGF21 is associated with improved systemic glucose homeostasis and memory formation. 406 This indicates that FGF21 not only plays a role in cellular stress responses but also has a significant role in regulating brain function and systemic metabolism. 406 Therefore, endogenous GLP-1R signaling in astrocytes plays a critical role in maintaining mitochondrial homeostasis and is dependent on FGF21 to effectively regulate glucose metabolism. 406 , 407

GLP-1RAs can alleviate neuroinflammation by acting on the nervous system, thereby offering additional relief from pain in patients. 6 , 409 , 410 During a previous experiment, researchers induced pain and observed symptoms of cognitive impairment in rats through spinal nerve ligation. Then, the researchers administered exendin-4 via intrathecal injection to the experimental rats and observed a reduction in pain sensitivity, alleviation of neural inflammation, and suppression of inflammatory factors such as IL-1β, TNF-α, and iNOS. This finding suggests a direct correlation between the analgesic effects of GLP-1R signaling and its Anti-neuroinflammatory activity. 411 In another study, 3D fluorescence microscopy was used to eliminate proteins within chondrocytes in the subchondral bone of cartilage, resulting in bone transparency and the acquisition of high-resolution 3D images. By utilizing this methodology, researchers have revealed that GLP-1RAs can exhibit affect the axon terminals of sensory neurons. Ultimately, it was revealed that cholinergic fibers are present within the subchondral bone of individuals with OA, and the release of acetylcholine (Ach) triggered by vagus nerve stimulation plays a prominent role in combating inflammation across various diseases while also providing pain relief. 412 Notably, GLP-1RAs, including exendin-4, have been shown to attenuate microglial activation, resulting in a reduction in the expression of proinflammatory cytokines such as TNF-α and IL-1β. By modulating inflammatory responses, GLP-1RAs can help prevent the degeneration of dopamine-producing cells. 413 GLP-1RAs play a neuroprotective role in neurons by facilitating neuronal survival and promoting neuronal growth, thereby preserving the structural and functional integrity of synapses. 6 , 14 Furthermore, GLP-1 signaling indirectly enhances and restores the insulin signaling pathway in neurons, leading to a reduction in the phosphorylation of insulin receptor substrates and the burden caused by monomeric α-synuclein. 414 Together, these effects contribute to the protection of dopaminergic neurons (source). Exenatide has been shown to mitigate the phosphorylation of insulin receptor substrates and the accumulation of monomeric α-synuclein. 414 By activating the GLP-1 signaling pathway, exenatide exhibits neuroprotective effects and safeguards dopaminergic neurons. 5

The most well-known mechanism through which GLP-1RAs affect weight loss is through the endocrine pathway, but its role in the nervous system should not be overlooked. 415 , 416 , 417 GLP-1RAs can exert their local effects by activating vagal dendritic terminals that innervate the gut. 418 , 419 , 420 This activation holds the ability to modulate food consumption by reducing food intake and conveying signals of satiety to the brain. 391 GLP-1 and GLP-1 analogs exert their effects on food intake and body weight through a myriad of neural substrates, encompassing several hypothalamic nuclei (including the arcuate nucleus of the hypothalamus, periventricular hypothalamus, and lateral hypothalamic area), hindbrain nuclei (such as the parabrachial nucleus and medial nucleus tractus solitarius), the ventral subregion of the hippocampus (vHP), and nuclei embedded within the mesolimbic reward circuitry (including the ventral tegmental area, VTA, and nucleus accumbens, NAc). 421 , 422 Remarkably, GLP-1R activation in certain nuclei (such as the VTA, NAc, and vHP) elicits reductions in food intake and body weight without concurrent nausea responses. 392

The relationship of inflammatory response and neurodegenerative disease

In the research conducted by Daniel J. Drucker’s team, the mechanism of anti-inflammatory action of GLP-1RAs was explored, revealing a key role for the CNS in regulating this anti-inflammatory effect. 423 The study began by inducing inflammation in mice through the injection of various Toll-like receptor (TLR) agonists and then assessed the inflammation by measuring plasma tumor necrosis factor-alpha (TNF-α) levels. 423 It was observed that the GLP-1RA, exendin-4, significantly reduced the TNF-α levels caused by various TLR agonists, indicating that exendin-4 can lower the TNF-α levels induced by multiple TLR agonists. 423 The research further demonstrated that this anti-inflammatory effect was not mediated by GLP-1R in the blood or endothelial cells but required the GLP-1R in the CNS.

Additionally, to simulate sepsis caused by polymicrobial infection and assess the impact of GLP-1RAs, the study utilized a cecal content injection method. It was found that semaglutide, a long-acting GLP-1RA, could improve symptoms caused by sepsis, reduce body temperature, and decrease the bacterial load in multiple organs, along with the levels of inflammatory factors in plasma and lungs. 423 These findings further confirmed the central role of the CNS in regulating the anti-inflammatory effects of GLP-1RAs, highlighting the potential application of GLP-1RAs in anti-inflammatory treatment.

The study also discovered the roles of α1-adrenergic and δ- and κ-opioid receptors in this process. Specifically, blocking the α1-adrenergic receptors with prazosin or the opioid receptors with nalbuphine interfered with the ability of GLP-1RAs to reduce plasma TNF-α levels, indicating the critical importance of these pathways in the anti-inflammatory effects mediated by GLP-1 activation. The α1-adrenergic receptors, found on the surface of cells, facilitate various physiological responses, including regulating vascular contraction and heart rate. The use of prazosin, an α1-adrenergic receptor blocker, showed that the ability of GLP-1RAs to reduce TNF-α in plasma was disrupted, signifying the vital role of α1-adrenergic receptors in the anti-inflammatory action of GLP-1RAs. Opioid receptors, which are associated with pain regulation, mood, and immune responses, include δ and κ types. The use of nalbuphine, a blocker of δ- and κ-opioid receptors, also disrupted the effect of GLP-1RAs on reducing TNF-α levels, highlighting the essential role of these opioid receptors in the anti-inflammatory effects mediated by GLP-1RAs. 423

Furthermore, the study emphasized that neurons in specific brain regions, such as the hindbrain and hypothalamus, co-express GLP-1R along with α1-adrenergic and δ-opioid receptors, suggesting a localized mechanism within the CNS that could coordinate peripheral anti-inflammatory responses. This co-expression indicates a mechanism within the CNS allowing these neurons to sense and respond to the peripheral inflammatory state. Through the interaction of these receptors, the brain can receive signals of peripheral inflammation and respond through neural signaling, thereby modulating or alleviating the inflammatory response. This receptor co-expression on neurons in specific brain regions may enable the brain to finely regulate the body’s response to inflammation. For instance, when peripheral tissues become inflamed, the related signals might be transmitted to the brain through these receptors on the neurons, and the brain could then respond to these signals via neural pathways, thus regulating the level of peripheral inflammation. 423

GLP-1RAs and AD

AD is a progressive and irreversible neurodegenerative disorder characterized by an unclear etiology and pathogenesis. 424 In AD, GLP-1(7-36) amide inhibits IL-1β transcription and prevents cognitive dysfunction, amyloid precursor protein synthesis, and cell death. It also enhances learning and memory by promoting long-term potentiation (LTP). 425 , 426 In a murine model of AD, the administration of GLP-1RAs effectively reduced the levels of pathological markers associated with AD. These markers include oligomeric antibodies and amyloid plaque load. Furthermore, GLP-1RAs have been shown to attenuate microglial activation and improve memory-related behaviors. 71 Moreover, GLP-1RAs have demonstrated considerable therapeutic promise in animal models of both PD and AD. 427 , 428 , 429 The compound NLY01 is particularly effective at attenuating the activity of proinflammatory microglia and preventing the transformation of astrocytes to a reactive phenotype. This activity is instrumental in safeguarding hippocampal neurons from the deleterious impacts of glutamate-induced excitotoxicity and hypoxic conditions. In the context of AD, where neuroinflammation and neurotoxicity are prominent pathological hallmarks, the modus operandi of NLY01 offers a potential therapeutic avenue to mitigate analogous pathological mechanisms inherent to this neurodegenerative condition. 430

GLP-1RAs and PD

PD is a chronic neurodegenerative disorder that affects the CNS and is the second most prevalent neurodegenerative disease worldwide. 14 GLP-1RAs are promising pharmacological agents for treating PD due to their potential to preserve the integrity and function of dopaminergic neurons. In addition to its effects on metabolic regulation, GLP-1, when synthesized within the brain, exhibits neuroprotective properties. 397 , 427 , 431 A clinical trial titled “Liraglutide in Early Parkinson’s Disease” was published in the New England Journal of Medicine, exploring the effects of liraglutide on patients with early-stage PD diagnosed within the last three years. 432 The research was a 14-month Phase II double-blind randomized controlled trial. The results showed that liraglutide had a modest positive effect on improving motor function and performed well in terms of safety and tolerability, although there were some manageable gastrointestinal side effects. 432 The study emphasizes the need for further research into the potential benefits and risks of liraglutide in patients at different stages of PD. 432

GLP-1RAs and addictive disorders

Researchers have discovered that semaglutide has the ability to reduce both recurrent alcohol consumption and overall alcohol intake in rats by more than 50%. 433 Specifically, alcohol-dependent rats were administered semaglutide, which resulted in a significant reduction in their alcohol consumption. 433 Further investigation into the mechanism underlying the alcohol-reducing effects of semaglutide suggested that this effect may involve the modulation of alcohol-induced rewards and punishments within the brain. Researchers have also shown that semaglutide impacts the reward and punishment systems in the brains of mice, particularly in the nucleus accumbens region, which is part of the limbic system. 433 It is believed that alcohol activates the brain’s reward and punishment system, triggering the release of dopamine, a neurotransmitter associated with pleasure and reward, both in humans and animals. However, the administration of semaglutide appeared to block this process, potentially leading to a diminished alcohol-induced reward and punishment response within the body. 433 Remarkably, compared with untreated rats, treated rats exhibited a significant reduction in alcohol intake, which was reduced by half. 433 These findings highlight the potential therapeutic efficacy of semaglutide in mitigating alcohol consumption. 434

Interestingly, a clinical study published in “Nature Metabolism” in 2023 investigated the restorative effects of liraglutide on impaired associative learning in individuals with obesity. The study utilized a single-blind, randomized, placebo-controlled, crossover design, combined with functional magnetic resonance imaging (fMRI), to analyze the performance of 54 participants (30 with normal insulin sensitivity and 24 with impaired insulin sensitivity) on sensory associative learning tasks while receiving liraglutide and placebo treatments. 435 Liraglutide significantly enhanced associative learning abilities in obese individuals with impaired insulin sensitivity. It modulated neural activity in the ventral striatum and midbrain pathways, affecting brain areas related to metabolic signaling. 435 , 436 Liraglutide improved task performance at the behavioral level and enhanced the encoding of adaptive prediction errors, which are crucial neural signals in the learning process. 435 (Fig. 5 ).

The effects of GLP-1RAs on nervous system. GLP-1RAs have diverse effects, including alleviating neuroinflammation and pain in OA, reducing food intake and improving body weight, protecting peripheral nerves, maintaining astrocyte function and metabolic homeostasis, and showing potential therapeutic benefits in AD and PD. Semaglutide, a diabetes drug, can also reduce alcohol consumption by modulating the brain’s reward and punishment systems

GLP-1RAs in the cardiovascular system

In the cardiovascular system, GLP-1 can reduce cardiac ischemia-reperfusion injury through the activation of specific signaling pathways, such as the PI3K/Akt pathway. 437 , 438 This involves modulating the cell apoptosis process, for example, by decreasing the Bax/Bcl-2 ratio in cardiomyocytes, reducing cytochrome C release, and caspase activation. 438 , 439 GLP-1 can also enhance endothelial function by promoting the production of NO, possibly through activating eNOS, thereby affecting vasodilation, anti-inflammatory actions, and anti-atherosclerosis. 43 , 192 , 440 , 441

GLP-1RAs and AS

AS is characterized by the formation of fibrofatty plaques within arterial walls and is one of the foremost global causes of mortality. 5 GLP-1RAs, as exemplified by liraglutide and semaglutide, exhibit pronounced cardiovascular protective effects. 43 Liraglutide and semaglutide have been demonstrated to be effective at reducing lipid and blood pressure levels through numerous scientific investigations, thereby contributing to the mitigation of AS and cardiovascular ailments. 442 Preclinical studies have documented the inhibitory effects of GLP-1RAs on the development of AS in animal models. 443 These agents exert their anti-atherosclerotic effects through various mechanisms, including by improving blood lipid profiles, 444 preserving endothelial integrity and regulating endothelial function, 445 as well as modulating inflammatory processes. 70

GLP-1RAs confer substantial benefits for individuals with AS owing to their multifaceted impact on various aspects of cardiovascular health. 39 , 40 , 446 Notably, GLP-1RAs exhibit pronounced efficacy in optimizing blood lipid profiles by effectively suppressing chylomicron secretion in the intestine, thereby mitigating the occurrence of postprandial hyperlipidemia. 447 Moreover, these agents promote hemodynamic equilibrium, 18 diminish thrombotic propensity, 448 alleviate endothelial oxidative stress, 449 attenuate inflammatory processes, 450 and foster a favorable balance of the gut microbiota, 451 all of which collectively contribute to the salutary effects of these agents in patients with AS.

GLP-1RAs have been shown to exert beneficial effects on the maintenance of endothelial integrity. One study suggested that GLP-1RAs exert direct endothelial protective effects by activating the GLP-1R-dependent AMPK/Akt/eNOS pathway. This pathway facilitates the generation of NO, thereby contributing to the preservation of vascular health and endothelial function. Additionally, GLP-1RAs facilitate the maintenance of endothelial barrier integrity, thus playing a crucial role in preventing vascular leakage. 452 Endothelial cells exhibit enhanced NO production and concurrent suppression of endothelin formation, resulting in vascular smooth muscle relaxation and vasodilation mediated by the endothelium (e.g., GLP-1, exenatide, and liraglutide). 453 Indeed, GLP-1RAs, including exenatide, liraglutide, and semaglutide, have been linked to the diminished expression of matrix metalloproteinases (MMPs). 454 , 455 , 456 MMPs are a class of enzymes that play a crucial role in the breakdown of extracellular matrix components. Excessive MMP activity can lead to the weakening of fibrous caps and increase the risk of plaque rupture in atherosclerotic lesions. 454 By reducing MMP expression, GLP-1R stimulation may help preserve the integrity of fibrous caps and mitigate the risk of plaque rupture.

GLP-1RAs have been shown to reduce the levels of systemic inflammatory markers. 457 , 458 Importantly, the effective management of inflammation is widely acknowledged to play a crucial role in the prevention of cardiovascular diseases. 459 , 460 The anti-inflammatory effects of GLP-1RAs contribute to the attenuation of atherosclerotic plaque lesion development through various mechanisms. First, GLP-1RAs have been shown to inhibit the expression and release of proinflammatory cytokines, such as IL-6 and TNF-α, thereby inhibiting the overall inflammatory response. 461 GLP-1RAs can suppress the activation of nuclear factor-kappa B (NF-κB), a key transcription factor involved in the regulation of inflammatory processes. 462 Inhibition of the NF-κB signaling pathway leads to the decreased production of inflammatory mediators, including adhesion molecules and chemokines, which are crucial for the recruitment of immune cells to sites of inflammation. 463 In addition, liraglutide can delay the formation of AS by inducing cell cycle arrest in vascular smooth muscle cells through the AMPK pathway. 5

GLP-1RAs and hypertension

The carotid body, a vital chemoreceptor in the human body, plays a pivotal role in the regulation of respiratory and cardiovascular activity, energy homeostasis, and blood glucose sensitivity. 464 Notably, the carotid body expresses GLP-1R, which is implicated in the concurrent regulation of blood pressure and blood glucose. 465 The downregulation of GLP-1R expression may represent a significant contributory factor to the co-occurrence of hypertension and hyperglycemia. 466 One study proposed a novel mechanism wherein postprandial GLP-1 release, under normal physiological conditions, inhibits the activity of chemosensory cells in the carotid body, thereby counteracting sympathetic excitability mediated by elevated blood glucose or insulin levels. 465 Impaired GLP-1 secretion or reduced GLP-1R expression may result in aberrantly heightened sympathetic excitation. However, the exogenous administration of GLP-1RAs can mitigate sympathetic excitability by suppressing the peripheral chemoreflex originating from the carotid body. 467 Under hyperglycemic conditions, GLP-1RAs regulate hypertension by inhibiting carotid body function. 468 Specifically, these agents can attenuate the excitability of carotid body cells and diminish sympathetic activation, ultimately leading to a reduction in sympathetic responses. 465 This modulatory effect holds promise for ameliorating sympathetic activity in individuals with hypertension, as these agents lower blood pressure levels. 469 Importantly, the “GLP-1-carotid body pathway” may represent a novel therapeutic target for managing cardiovascular metabolism and treating patients with diabetes and hypertension who exhibit heightened sympathetic activity. 465 (Fig. 6 ).

The Effects of GLP-1RAs on Carotid Body Activation. GLP-1 by inhibiting the chemoreception in carotid body cell activity to adjust the new mechanism of sympathetic nerve excitability, and points out that GLP-1 agonists can inhibit the origin of the carotid body around chemical reflection to lighten the sympathetic nerve excitability, which is expected to improve the sympathetic activity of the patients with high blood pressure, reduce blood pressure levels

GLP-1RAs and heart failure

The prevalence of left ventricular ejection fraction (LVEF)-preserved heart failure continues to increase. The symptoms in patients are severe and often accompanied by functional impairments, especially in the obese population. Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases, with patients bearing a high symptomatic burden and physical limitations that impact their daily lives. These limitations include fatigue, shortness of breath, reduced exercise capacity, and limb swelling. Currently, there are no approved targeted therapies for LVEF-preserved heart failure associated with obesity. Moreover, GLP-1R has not yet been identified on human myocardial cells, negating any direct effects of GLP-1RAs on myocardial cells. 470

Recently, studies have shown that the GLP-1RA Meg peptide also enters the ejection fraction reserve following heart failure therapy. The results of a trial of semaglutide in obese patients with HFpEF showed a significant amelioration of symptoms and improvements in motor function and weight loss compared with patients treated with a placebo. 470 In this study, researchers randomized 529 patients with heart failure with a preserved ejection fraction and body mass index (weight in kilograms in the square of the height in meters) ≥30 to receive once-weekly injections of semaglutide (2.4 mg) or placebo for 52 weeks. The two primary endpoints were the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, which ranges from 0 to 100) and the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Higher scores indicate fewer symptoms and physical limitations and weight change from baseline. The confirmatory secondary endpoints included the change in the 6-min walking distance, a hierarchical composite of death and heart failure events; the difference between the change in the KCCQ-CSS and the change in the 6-min walking distance; and the change in the C-reactive protein (CRP) level. 470 In this trial, semaglutide benefited patients with heart failure and preserved ejection fraction by intervening with upstream metabolic drivers. This agent differs from earlier therapies that were designed to reduce myocardial loading or induce neurohumoral blockade. These positive results indicate that the change in myocardial cells may not be the primary driver of HFpEF; instead, the multisystem pathologic processes that are associated with this condition have long been well established as drivers of its clinical presentation and outcomes. 470

One could argue that the success of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and now of GLP-1RAs, suggests that metabolic abnormalities play an important role in driving HFpEF. 470 SGLT2 inhibition is also known to benefit patients with heart failure and a reduced ejection fraction. 471 The mechanisms by which SGLT2 inhibitors treat heart failure include lowering blood glucose levels by inhibiting the SGLT2 protein in the renal tubules and reducing glucose reabsorption in the tubules. 472 Promoting the urinary excretion of sodium and water reduces fluid retention and hypervolaemia, thereby reducing the load on the heart. 473 It also improves myocardial energy metabolism, increases fatty acid oxidation in the myocardium, and improves myocardial energy supply. 474 Moreover, these agents reduce the risks of myocardial inflammation and fibrosis and improve cardiac structure and function. 475 By the way, a clinical study published in “Nature Metabolism” detailed the effects of semaglutide and dapagliflozin (an SGLT2 inhibitor) on blood sugar control in patients with T2DM of different pathophysiological types. 476 It was found that semaglutide performed better than dapagliflozin in reducing HbA1c levels. 476 The study results suggest that semaglutide may be a more suitable choice for patients with severe insulin deficiency, while dapagliflozin might be effective for a broader range of patients with metabolic abnormalities. 476

If SGLT2 inhibitors and GLP-1RAs are effective in patients with heart failure (regardless of whether the ejection fraction is reduced or preserved), the commonalities between the two types of heart failure may be greater than is often thought. If so, the two types of heart failure may be very similar, except that the cause of heart failure with a preserved ejection fraction may not be the same as that with a reduced ejection fraction. 477 , 478 , 479 If this is indeed the case, then both types of heart failure are syndromes caused by multiple metabolic and inflammatory changes; however, heart failure with reduced ejection fraction also has a regional cause. Therefore, intrinsic cardiac load and capacity do not improve in patients with heart failure with reduced ejection fraction, and patients HFpEF benefit only from the treatment of abnormal metabolism and inflammation. 475 , 480 , 481

The encouraging results obtained with semaglutide in patients with heart failure and a preserved ejection fraction may provide a new option for this patient population, in which additional therapy, as well as another upstream therapy for patients with a higher BMI who have indications for this condition, is urgently needed. The clinical translation of these trial results, which will be important for the comparison of GLP-1RAs with SGLT2 inhibitors in the treatment of patients with heart failure and a preserved ejection fraction, remains to be determined. 470 , 478 , 482 , 483 , 484

GLP-1RAs in the digestive system

Treatment with GLP-1RAs can alleviate insulin signaling by reducing the phosphorylation of Akt protein (Decreased Akt-P) and activating Protein Kinase C-ε (PKC-ε). 485 , 486 This affects the synthesis of triacylglycerol (TAG), phosphatidic acid (di-P PA), and diacylglycerol (DAG) in the liver. 206 , 487 These changes lead to a reduction in the production of non-esterified fatty acids (LCFAs) and glucose, as well as a decrease in the synthesis of VLDL (Very Low-Density Lipoprotein). 3

GLP-1RAs and NAFLD/NASH

When dietary nutrients are ingested, endogenous incretins (GIP and GLP-1) activate K and L cells in the gut, which then secrete GIP and GLP-1. 488 , 489 , 490 In the pancreas, this stimulates the secretion of insulin and inhibits the secretion of glucagon. 491 In the brain, it reduces appetite and improves satiety. 130 , 133 In the gastrointestinal tract, it lowers the synthesis and secretion of triglycerides. 491 By regulating appetite, insulin secretion, and lipid metabolism, GLP-1RAs have potential benefits in the treatment of NAFLD, NASH, and T2DM. 130 , 492 , 493

NASH is a liver disease primarily caused by fat accumulation, which can progress to liver fibrosis, cirrhosis, or even liver cancer. 494 , 495 , 496 , 497 , 498 The role of GLP-1 in NASH has garnered attention due to its potential in regulating metabolism, improving insulin sensitivity, and exerting anti-inflammatory effects. 17 , 499 , 500 , 501 , 502 , 503 Insulin resistance, a common occurrence in NASH patients, is a key driver of the disease’s progression. 504 , 505 , 506 GLP-1 enhances the insulin signaling pathway in the liver by activating the GLP-1R, especially through the phosphorylation of insulin receptor substrates and the activation of the PI3K/Akt signaling pathway, thereby increasing hepatic insulin sensitivity, facilitating glucose uptake and utilization, and reducing hepatic gluconeogenesis. 3 , 507

GLP-1RAs reduce liver fat accumulation by activating AMPK, which inhibits fatty acid synthesis enzymes and promotes fatty acid β-oxidation, thus diminishing lipid droplet accumulation in hepatocytes. 508 , 509 , 510 , 511 Additionally, GLP-1 mitigates liver inflammation and fibrosis by inhibiting the NF-κB pathway, reducing the release of pro-inflammatory cytokines such as TNF-α and IL-6, and thus suppressing inflammatory pathways. 307 , 413

In terms of apoptosis inhibition, GLP-1 activates the PI3K/Akt signaling pathway, enhances the expression of the anti-apoptotic protein Bcl-2, and inhibits the activation of caspase family proteins, reducing cell apoptosis. 206 This helps prevent the progression of NASH to liver fibrosis and cirrhosis. The weight-loss effect of GLP-1RAs also benefits NASH improvement, by reducing appetite and increasing energy expenditure to promote weight loss, thereby indirectly ameliorating NASH. 206 , 512 Thus, GLP-1 and its agonists slow down the progression of NASH and may positively impact the reversal of liver fibrosis. 513 , 514 These signaling pathways suggest that GLP-1 and its receptor agonists may influence the progression of NASH through multiple mechanisms, providing several potential therapeutic targets including: FOXO1, a transcription factor that plays a critical role in regulating glucose and lipid metabolism. GLP-1 can improve abnormalities in glucose metabolism and excessive lipid accumulation by modulating the activity of FOXO1. 5 , 514 Sirt1, a protein deacetylase, plays a key role in delaying cellular aging and regulating metabolism. 515 , 516 , 517 GLP-1 may improve the liver’s antioxidant capacity and metabolic function by activating Sirt1, thereby helping to alleviate the pathological changes associated with NASH.

A 2023 study published in the “Journal of Hepatology” reported on a Phase IIa trial aimed at evaluating the efficacy and safety of efinopegdutide in patients with NAFLD, comparing it to semaglutide. 144 Efinopegdutide is a dual agonist for GLP-1R and GIPR. 144 The study used a randomized, open-label design and employed magnetic resonance imaging technology (MRI-PDFF) to measure liver fat content (LFC) after 24 weeks of treatment. Results showed that efinopegdutide was more effective in reducing LFC compared to semaglutide. Additionally, the study assessed weight and metabolic responses, finding that efinopegdutide’s tolerability was similar to that of semaglutide, although certain gastrointestinal side effects were more common. Overall, efinopegdutide emerged as a promising option for the treatment of NAFLD. 144

GLP-1RAs and gastrointestinal cancers

GLP-1 and its receptor agonists show some potential in the treatment of gastrointestinal cancers, although this remains an emerging area of research. 518 , 519 , 520 , 521

Hepatocellular carcinoma (HCC)

Initially developed for treating diabetes, GLP-1RAs have shown potential in treating NASH, which is closely related to HCC. 513 Studies suggest that the anti-inflammatory and metabolic effects of GLP-1RAs might also influence the progression of liver diseases, including HCC. 503 , 512 , 518 These effects include modulating cell proliferation, inflammation, and oxidative stress in liver cells, all of which are key factors in the development and progression of HCC. 513 , 522 In a mouse model induced with NASH-related HCC, treatment with liraglutide (a type of GLP-1RA) was shown to prevent the progression of hepatocellular carcinoma. 518 This was observed through improved glycemic control, reduced occurrence of liver cancer, and better liver histology compared to the control group. 518 Studies indicate that liraglutide may inhibit liver carcinogenesis through its metabolic effects, suggesting that GLP-1RAs could potentially play a role in preventing or managing HCC in the context of NASH. 523 Not only hepatocellular carcinoma, but GLP-1 has also shown potential in the treatment of other gastrointestinal tumors. 524 , 525

Pancreatic cancer

Researchers first compared the expression of GLP-1R in human pancreatic cancer tissues with adjacent non-tumorous pancreatic tissues, finding generally lower or absent expression of GLP-1R in pancreatic cancer tissues. 520 Subsequently, the study observed that treatment with liraglutide, both in vitro (cell culture models) and in vivo (mouse models), inhibited the tumor formation and metastatic capabilities of pancreatic cancer cells by activating GLP-1R. 520 The anti-tumor effect of liraglutide is related to its inhibition of the PI3K/Akt signaling pathway, as the activation of Akt is crucial for promoting cell survival and proliferation, and liraglutide can inhibit this process in a dose-dependent manner. 520 , 526 In the context of T2DM, liraglutide, by regulating the PI3K/Akt pathway and activating GLP-1R, effectively inhibits the growth and spread of pancreatic cancer cells. 520

Colorectal cancer

The potential impact of GLP-1RAs on colorectal cancer (CRC) treatment is achieved through the modulation of Bone Morphogenetic Protein 4 (BMP4). 519 In T2DM and CRC, the regulation of BMP4 is abnormal, which is a key focus of the research. 519 Specifically, high blood glucose-induced insulin resistance in CRC cells leads to increased BMP4 expression, which activates the BMP4-Smad1/5/8 signaling pathway. 519 The activation of this pathway enhances cell proliferation and metastatic capabilities by promoting epithelial-mesenchymal transition (EMT), thereby increasing the invasiveness and metastatic potential of tumors. However, GLP-1RAs have been shown to reduce BMP4 levels through exogenous administration. Studies have shown that treating CRC cells with GLP-1RA can inhibit cell proliferation induced by insulin resistance by downregulating BMP4. Therefore, BMP4 becomes a potential therapeutic target in CRC, especially in a diabetic context where high blood glucose significantly affects cancer progression through the BMP4 pathway. 519 Ultimately, GLP-1RA, by regulating BMP4 and its effects on cell proliferation and metastasis, provides a promising treatment approach. 519 This not only demonstrates the role of GLP-1RA in diabetes management but also offers potential for integrating diabetes and cancer treatment. 520 This finding emphasizes the importance of considering metabolic status in cancer treatment and the necessity for further research in this area. 519 While early models have shown promising results, the application of GLP-1RAs in cancer treatment has not yet been established and requires further clinical trials. 527

Conclusions and perspective

Primarily recognized for their role in diabetes mellitus treatment, GLP-1RAs have demonstrated significant benefits in cardiovascular health, skeletal muscle-related diseases, obesity management, and neurodegenerative conditions, among others. In this review, we delved into the multifaceted role of GLP-1R, especially its significance in disease contexts beyond traditional glucose metabolism. It explored the mechanisms of action of GLP-1RAs and their therapeutic potential in a wide array of diseases, such as diabetes mellitus, providing new insights into metabolic disease management. These findings underscore the multifunctionality of GLP-1R as a therapeutic target and its involvement in various biological processes, emphasizing its role in addressing complex disease mechanisms. GLP-1 acts on the GLP-1R, activating multiple intracellular signaling pathways, including the cAMP/PKA pathway, the PI3K/Akt signaling pathway, and pathways related to anti-inflammatory and anti-oxidative stress responses, among others. These pathways play a crucial role in its wide-ranging therapeutic effects, extending the benefits of GLP-1RAs beyond metabolic diseases. While the therapeutic benefits of GLP-1RAs in diabetes management are well-established, their emerging role in other diseases suggests novel treatment strategies. Conclusively, research on GLP-1R and its agonists marks a promising direction in metabolic disease therapy, extending their potential beyond glucose regulation and offering hope for more comprehensive approaches in addressing metabolic diseases. This research necessitates continued exploration, potentially revolutionizing future therapeutic strategies.

In the intensely competitive GLP-1 drug market, simply enhancing drug efficacy is no longer sufficient to make new products stand out. Looking ahead, the key strategies for product innovation and differentiation are likely to focus on five main directions: expanding the therapeutic indications, achieving precision treatment with multiple biological targets, optimizing the clinical application of drug combinations, developing new formulations of oral medications, and extending the duration of drug action. These strategies not only illustrate the depth and breadth of pharmaceutical research but also signify the frontier of future medical innovations. Firstly, expanding indications is a current hotspot in GLP-1 drug research. GLP-1 drugs have been found applicable for various diseases such as cardiovascular disease, NASH, AD, and chronic kidney disease. For instance, semaglutide has been approved and is being researched for indications including obesity, T2DM, reducing cardiovascular risk, chronic kidney disease, NAFLD, and AD, indicating that the development of new indications could provide new growth opportunities for GLP-1 drugs. Secondly, efficacy is the core criterion for evaluating drugs, and currently, multi-target GLP-1 drugs have shown better efficacy. For example, triple-target agonists like retatrutide are leading multi-target GLP-1 drugs. Moreover, combination therapies have demonstrated significant advantages, such as Novo Nordisk’s CagriSema (semaglutide + cagrilintide), which shows superior glycemic control and weight reduction effects compared to semaglutide alone, demonstrating that combination therapy can achieve more than the sum of its parts while reducing side effects. 117 Additionally, to improve patient compliance, it is crucial to extend the drug’s half-life. This has been achieved through techniques such as peptide sequence modification, peptide lipidation, albumin fusion, and Fc fusion. For example, scientists are developing GLP-1 drugs that require only monthly injections. Lastly, considering some patients’ resistance to injections, oral medications have become the preferred option. However, the oral GLP-1 product, Rybelsus, has low bioavailability and requires cumbersome daily administration, which reduces its convenience. Therefore, enhancing bioavailability and stability will be key in the future, although breakthroughs in once-weekly oral GLP-1 drugs are still awaited. With the increasing prevalence of metabolic diseases globally, interventions targeting GLP-1R could play an important role in reducing the burden of these conditions. Collaborative efforts among researchers, clinicians, and pharmaceutical developers are essential to translate these scientific insights into effective and accessible treatments.

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Acknowledgements

This study was performed with the support of the National Natural Science Foundation of China (82002339, 81820108020), Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System (BJ1-9000-22-4002). BioRender ( https://www.biorender.com/ ) was used to create the Fig. 2 .

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These authors contributed equally: Zhikai Zheng, Yao Zong

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Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China

Zhikai Zheng, Yiyang Ma, Yucheng Tian, Yidan Pang, Changqing Zhang & Junjie Gao

Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China

Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, WA, 6009, Australia

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Z.Z., Y.Z. and J.G. drafted and conceived the initial manuscript. J.G. and C.Z. provided the essential assistant for our final manuscript. Z.Z., Y.M., Y.T., Y.Z. and Y.P. drew the figures and arranged the tables. All authors have read and approved the article.

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Zheng, Z., Zong, Y., Ma, Y. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9 , 234 (2024). https://doi.org/10.1038/s41392-024-01931-z

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DOI : https://doi.org/10.1038/s41392-024-01931-z

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The Dangers of Uncontrolled Immigration

The alarming current intensity of migration to Europe, along with the weak reaction that fuels the "woke" mentality entrenched in all layers and institutions, makes this wave of migration very different from previous ones and represents a true threat to the soul—and soon to the institutional body—of our Western, Judeo-Christian, and liberal civilization.

As of June 7, 2024, for the first time in the history of Spain, the prison population of young people born abroad exceeds that of young Spaniards in prison, at a ratio of 60 to 40. If we include those born in Spain with Spanish nationality but to foreign parents, that ratio skyrockets to over 70/30. And if we distinguish by categories of crimes, we will find that most convictions for rape and sexual assault fall on foreigners, following an exponential increase in this type of crime in recent years. 

Europe—and Spain—are historically accustomed to large population movements, and perhaps for this reason, they view the new wave of immigrants arriving on their shores with a certain benevolence and naivety. Past migrations occurred within the same civilization, religion, and culture, while the new migratory wave almost always and predominantly comes from Muslim countries and sub-Saharan Africa, which are very distant, if not opposed, to the liberal values, gender equality, and freedoms of the Western world. This fact is overshadowed by a benevolent perspective that grants every immigrant the right to come to Europe, to enjoy the welfare state built and paid for by Europeans over decades, and to welcome them as if they were all refugees fleeing from armed conflicts.

The conjunction of a business class interested in cheap labor, the guilt complex of a political elite, with leaders like Angela Merkel who opened European borders wide in 2015, and an anti-capitalist left that, in the absence of a proletariat to follow it, pursues a de facto alliance with political Islam, means that merely presenting data reflecting a different reality is considered a hate crime, racism, or xenophobia. The alarming current intensity of migration to Europe, along with the weak reaction that fuels the "woke" mentality entrenched in all layers and institutions, makes this wave of migration very different from previous ones and represents a true threat to the soul—and soon to the institutional body—of our Western, Judeo-Christian, and liberal civilization.

Spain as an example

In 1996, there were 542,314 foreigners registered in Spain. Most came from Northern European countries and the United Kingdom—retirees with dual residency who came to enjoy long stays or their retirement in the benefits of the Spanish climate. They represented 1.4% of the total population at that time. During the 8 years of the first conservative government of Spanish democracy, the economy experienced unprecedented growth, and Spain became an attractive destination for those wanting to work and enjoy better opportunities. Thus, by 2004, when the Socialist Party returned to power, the foreign population had multiplied sixfold, reaching just over 3 million. The conservative government encouraged this growth driven by an economic vision (more workers and more consumers should fuel more prosperity) and because during these years most immigration to Spain came from Latin America. And as was often argued back then, they shared with Spaniards the same religion, attachment to family institutions, and individual values. What was not mentioned was that the value placed on life differed substantially and that the risk of crime associated with "maras" and other criminal organizations was irresponsibly dismissed.

Since 2004, with very few exceptions linked to the deep economic crisis generated by the Socialist government of Rodríguez Zapatero (2004-2011), immigration has continued to rise. The latest census from 2022 places it at over 5.5 million (almost 12% of the total population), and estimates for 2024 range from 6.5 million to 7.5 million, depending on who is counting around 15% of the population.

What the raw numbers do not reveal is the qualitative change that is occurring: Immigration from Latin America is slowing down, immigration from the European Union is plummeting, while immigration from Africa is rocketing up. In 2022, the largest minority of immigrants in Spain came from Morocco, with nearly one million people. Today, that number could already be at 1.2 million, despite the strong push for naturalizations granted by the current socialist-communist government, which tends to favor Moroccans (30% of the total in 2021).

Even worse, the economic argument that justified previously unseen levels of immigration—now supplemented by the need for young workers to support an aging population and our pension system—remains a fallacy when it is confirmed that most of these new immigrants do not contribute anything to state coffers but rather consume public resources. Thus, according to data from the Social Security Ministry at the end of 2023, only 35% of Moroccans settled in Spain were contributing to social security; the same was true for Nigerians; and barely 25% for Algerians.

The only independent study that analyzed the costs and benefits of immigration in Spain was conducted by the Strategic Studies Group (GEES) in 2018 [1] , and although raw data may have changed, I do not believe its conclusions have been altered at all: The only foreign community in Spain with a higher employment rate than nationals is the Chinese community. The unemployment rate for those originating from North Africa triples or quadruples that of Spaniards, depending on the specific nationality.

In terms of direct costs, it is important to remember that due to the quasi-federal system of the Spanish state and the lack of communication between local institutions, autonomous communities, and state authorities, it is practically impossible to know how much public money is spent on the aid and social benefits offered for free to illegal immigrants. We do know, for example, that the Community of Madrid allocates about 6,000 euros a month to take care of each unaccompanied minor (around 15,000 in reception centers). However, what we do not know is the number of benefits that the rest of the immigrant population accumulates. Only in scandalous cases do we gain access to information; for instance, in 2014 it was revealed that Redouan Bensbih, a Moroccan enrolled in an Al-Qaeda franchise in Syria who died that year, received nearly 1,000 euros a month in integration aid from social services in the Basque Country for five years. In 2017, another jihadist, Said Lachhab, was arrested while receiving social benefits worth 1,800 euros. Another example: the first hundred names on the list of 300 housing aids granted by the Community of Madrid (under conservative governance) are all North Africans. Some claim that the direct cost of illegal immigration in Spain amounts to ten times the defense budget—80 billion euros a year. This is something to consider when discussing the economic benefits of immigration.

But there is another social factor that must be kept very much in mind: crime associated with immigration. The subject is anathema for the left and a toxic topic for conventional right-wing parties that do not want to be labeled as xenophobic. But the data speaks for itself: according to figures from the National Institute of Statistics and those provided by the Supreme Council of Justice, in 2022 convictions of foreigners in Spain accounted for 26% of the total. By 2023, this figure exceeded 31%. This means that the immigrant population in Spain commits three times more crimes than native Spaniards. This issue worsens when we talk about sexual offenses, where foreigners commit crimes four times more often than Spaniards (seven times more when it comes to rapes) [2] . 

However, the most serious problems are not just the disparity in propensity to commit crimes between foreigners and nationals but also—as we are seeing these days with stark clarity in the United Kingdom—the double standard employed by police and judicial systems when dealing with immigrants. It is not only about different sentences being handed down for the same crime based on race, religion, or nationality; it also involves discriminatory police treatment against Catholics and Christians compared to Muslims, against whites compared to immigrants of color, and against nationals compared to foreigners—regardless of whether they are legal or illegal.

European media, in turn, respond to directives not to publish either the faces or the nationalities of criminals if they are immigrants or Muslims in order to avoid an increase in racism, it is said. However, they do not hesitate to highlight data when native Europeans are the ones committing crimes. The issue of gender-based violence is paradigmatic in this regard.

In Spain, when immigration involves believers—mostly evangelical Christians from Latin America—faith is practiced within the usual separation between Church and State. However, when Muslim minorities reach a certain threshold, they attempt to impose their customs regardless of the social friction this generates. This includes prayers blocking streets; demands for the removal of certain foods in schools and prisons; acceptance of being governed by Sharia law; and the imposition of animal sacrifices that should scandalize animal rights activists. But it does not stop there. As we have observed and suffered in major capitals around the world (with no American exception), tolerance towards the Muslim Brotherhood and political maneuvering by Hamas and its supporters have made the streets dangerous for Jews and for any decent European who aspires to continue living freely as before. Not to mention the illegitimate pressures on parliamentarians and government members.

The infamous Arab or Muslim Street has moved from the Middle East to the West with the acquiescence of timid conservatives and the complacency of a childish and nihilistic left. The local elections in 2024 in the United Kingdom show the future of Europe and the emergence of Muslim religious parties that aim to gradually take power from the bottom up.

The Suicide of Europe (and Spain)

Within Spain, there is a special place, Catalonia, that reveals how far the stupidity of current political and business leaders can go. Immersed in an ideology that seeks independence from the rest of Spain, their social policies have been oriented towards attracting immigrants who are not Spanish-speaking, prioritizing Pakistanis and Africans over Latin Americans. It was supposed that this would allow them to advance more quickly with their linguistic cleansing of Spanish. The result has been a disproportionate increase in Muslim communities and the highest rates of jihadism and crime among foreigners compared to the rest of Spain. It is in Catalonia where foreign convicts exceed Spaniards in all age categories. Today, Barcelona resembles Marseille and Tangier more than Copenhagen or Milan.

As British essayist Douglas Murray warned in his prescient book  The Strange Death of Europe [3] , it is the current weakness of Europe—the rejection of everything European by a significant part of the ruling class and the entire left, the social condemnation of practicing Christianity, and the ideological disarmament against Islamism—that makes this new wave of immigration so dangerous. One does not need to believe in the great replacement theory to see the disparity in birth rates between European women and those from Muslim countries. In Spain, for example, Spanish women have a fertility rate of 1.1 children per woman, while Moroccan women have 3.4. In other words, the growth of the Spanish population is due to the birth of babies to foreign parents, while the actual native population is decreasing. And continuing with the case of Catalonia, there are municipalities like Salt (in Girona), where births to foreign parents reach 75.7%.

Another point to consider: in Spain in 1970, not so long ago, more than 90% of the population identified as Catholic, with more than half also considering themselves practicing Catholics. By 2022, those figures had fallen to 37.2% and a meager 18%, respectively. By 2024, Spain will cease to be predominantly Catholic. Only evangelical Christians and Muslims are growing, but not so much due to conversions as driven by migration flows. Not far off, there will be more faithful on Fridays in mosques than Catholics at Mass on Sundays.

A population that has fundamentally turned its back on its faith cannot understand the religious motivations of others—much less those of Islam. This partly explains the difficulty in accepting the true challenge and risks posed to us Westerners—Europeans and Spaniards—by an open borders policy and uncontrolled immigration. But without that understanding, there is no strength or motivation that can save us.

Rafael L. Bardají served as National Security Advisor to the Spanish Prime Minister José Maria Aznar (1996-2004), director of the Net Assessment Office at the Spanish Ministry of Defense  (2012), and  CEO of World Wide Strategy, a consulting firm since 2013.

[1] GEES: El coste de la inmigración extranjera en España . Madrid, GEES 2018

[2] Ministerio del Interior: Informe general 2022 . Gobierno de España 2022

[3] Murray, Douglas. The Strange Death of Europe .   Bloomsbury Continuum; Updated edition (June 2018.

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