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Top 7 Research Summary Templates with Samples and Examples

Kavesh Malhotra

Turning complex research into a compelling summary is like having a superpower in the vast world of information. A well-crafted research summary isn't just a data crunch; it's a strategic tool. Research shows that concise summaries enhance understanding. Studies reveal that audiences retained 50% more information when presented with well-structured summaries.

Imagine condensing your extensive research into a single page that instantly captivates the reader's attention and highlights the core of your findings. Whether presenting a market research proposal, diving into clinical medicine research, or outlining a project research proposal, a smartly crafted research statement can make your work convenient, accessible, and impactful.

In this blog, we'll guide you through a curated selection of seven Research Summary Templates, each a gem in its own right.

Why Choose Research Summary Templates?

"Efficiency is the soul of every impactful presentation."

• Time-Saving Marvels:  These presets are your express pass to creating professional, impactful presentations that save you so much time and energy that would otherwise be spent making a summary from scratch!
• Customizable Frameworks:  Tailor each layout to suit your unique research, maintaining flexibility while leveraging a solid starting point.
• Visual Appeal:  The slides are not just functional; they are visually engaging, ensuring that your  research paper  doesn't just get read but leaves a lasting impression.

Let’s begin exploring these templates!

Template 1: Market Research Proposal One-Page Summary Presentation Report Infographic PPT PDF Document

This preset is a game-changer for presenting  market research proposals  concisely. It encapsulates your research's key aspects in a one-page summary, making a compelling case for readers. It includes details about the project name, researcher's information,  and project research proposal  details like background, objectives, methodology, and outcomes. Visual elements and a well-organized structure enhance readability, effectively communicating your market insights. Download this preset that transforms your  market research proposal  into a concise yet comprehensive summary, guiding your stakeholders through the essentials.

DOWNLOAD NOW

Template 2: Executive Summary Clinical Medicine Research Company Profile

For clinical medicine researchers, this layout provides a succinct yet comprehensive overview. The  executive summary  format communicates vital information, making it ideal for quickly understanding the research's significance. The slide depicts the company outline, critical statistics, and financial overview. The significant facts covered are the employee count, number of regulatory approvals, global market share, revenue CAGR, total revenue, and market capitalization. Elevate your  clinical medicine research  with an executive summary that encapsulates the essence of your findings and the potential impact on the medical landscape.

Template 3: Sample Research Paper Outline in One-Page Summary Report

This structure streamlines your detailed  research paper  into a digestible one-page summary. It breaks down the research paper's structure, ensuring the audience grasps vital points efficiently. It encapsulates five main sections: introduction, issue, literature review, recommendations, and conclusion. The easy-to-follow format makes it a valuable tool for presenting a complex  research statement.  Download this layout that transforms your detailed  research paper  into a  one-page summary  wonder, clearly presenting the structure and key points.

Template 4: One-Page Summary for Business Excellence Models Research Paper

Condense your exploration of business excellence models into a single, impactful page. This slide highlights the introduction,  executive summary , company background, financial information, business excellence model used, key findings and insights, and conclusion, presenting them aesthetically pleasing. It's perfect for delivering the essence of your business excellence research with clarity and brevity. Condense your exploration of business excellence models into a single page, making your insights accessible and actionable.

Template 5: One-Page Project Research Proposal Summary Presentation

Efficiently communicate the crux of your  project research proposal  with this preset. It highlights crucial components of your project research like objectives, study design, budget, project milestones and durations, etc. The  one-page summary  format ensures that your proposal's key elements are prominently featured. Visual elements enhance engagement, ensuring that key stakeholders swiftly grasp your project's significance. Download this layout and make it an excellent choice for a compelling project research presentation.

Template 6: One-Page Research Paper Summary on Business Ethics and Corruption

Navigate the complex landscape of business ethics and corruption research with this template. It condenses your  research paper  into a  one-page summary , focusing on crucial ethical considerations:

• Introduction of the concept
• sources of corruption in businesses
• The legislative framework
• Principals of ethics
• Conclusion and
• Customer viewpoint

Clear visuals and a cohesive layout ensure that your insights on ethics and corruption are communicated effectively, giving your  research statement  the attention it deserves. Download this  one-page summary , ensuring readers grasp your project's significance swiftly.

Template 7: Research Statement One Page Summary with Future Goals

Craft a compelling narrative of your research journey, culminating in a  one-page summary  with future goals. This presentation seamlessly integrates your  research statement  with a forward-looking perspective. It offers an overview of past and future research approaches and future goals to be achieved, along with a visual flowchart presenting your  project research proposal , research activity, and other written content. Download this powerful tool for presenting your research's impact and future directions.

Conclusion: Your Research, Your Way

In the world of academia, business, or healthcare, your research is a cornerstone of progress. Ensure it's not just buried in volumes of data but presented in a way that captivates and communicates. Explore the above research summary templates and transform your research journey into a resonant narrative. Furthermore, dive into the past with our  top history research proposal examples , complete with templates and samples for your historical research endeavors.

Remember, brevity is not just appreciated in a world saturated with information; it's often indispensable. So,  here , you can streamline your  project research proposals  with our top 7 one-page templates for compelling and concise presentations.

Craft your research summary with care, and let your findings shine!

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What’s Included: Research Paper Template

If you’re preparing to write an academic research paper, our free research paper template is the perfect starting point. In the template, we cover every section step by step, with clear, straightforward explanations and examples .

The template’s structure is based on the tried and trusted best-practice format for formal academic research papers. The template structure reflects the overall research process, ensuring your paper will have a smooth, logical flow from chapter to chapter.

The research paper template covers the following core sections:

• The title page/cover page
• Abstract (sometimes also called the executive summary)
• Section 1: Introduction 
• Section 2: Literature review 
• Section 3: Methodology
• Section 4: Findings /results
• Section 5: Discussion
• Section 6: Conclusion
• Reference list

Each section is explained in plain, straightforward language , followed by an overview of the key elements that you need to cover within each section. We’ve also included links to free resources to help you understand how to write each section.

The cleanly formatted Google Doc can be downloaded as a fully editable MS Word Document (DOCX format), so you can use it as-is or convert it to LaTeX.

FAQs: Research Paper Template

What format is the template (doc, pdf, ppt, etc.).

The research paper template is provided as a Google Doc. You can download it in MS Word format or make a copy to your Google Drive. You’re also welcome to convert it to whatever format works best for you, such as LaTeX or PDF.

What types of research papers can this template be used for?

The template follows the standard best-practice structure for formal academic research papers, so it is suitable for the vast majority of degrees, particularly those within the sciences.

Some universities may have some additional requirements, but these are typically minor, with the core structure remaining the same. Therefore, it’s always a good idea to double-check your university’s requirements before you finalise your structure.

Is this template for an undergrad, Masters or PhD-level research paper?

This template can be used for a research paper at any level of study. It may be slight overkill for an undergraduate-level study, but it certainly won’t be missing anything.

How long should my research paper be?

This depends entirely on your university’s specific requirements, so it’s best to check with them. We include generic word count ranges for each section within the template, but these are purely indicative. 

What about the research proposal?

If you’re still working on your research proposal, we’ve got a template for that here .

We’ve also got loads of proposal-related guides and videos over on the Grad Coach blog .

How do I write a literature review?

We have a wealth of free resources on the Grad Coach Blog that unpack how to write a literature review from scratch. You can check out the literature review section of the blog here.

How do I create a research methodology?

We have a wealth of free resources on the Grad Coach Blog that unpack research methodology, both qualitative and quantitative. You can check out the methodology section of the blog here.

Can I share this research paper template with my friends/colleagues?

Yes, you’re welcome to share this template. If you want to post about it on your blog or social media, all we ask is that you reference this page as your source.

Can Grad Coach help me with my research paper?

Within the template, you’ll find plain-language explanations of each section, which should give you a fair amount of guidance. However, you’re also welcome to consider our private coaching services .

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Research Summary: What is it & how to write one

The Research Summary is used to report facts about a study clearly. You will almost certainly be required to prepare a research summary during your academic research or while on a research project for your organization.

If it is the first time you have to write one, the writing requirements may confuse you. The instructors generally assign someone to write a summary of the research work. Research summaries require the writer to have a thorough understanding of the issue.

This article will discuss the definition of a research summary and how to write one.

What is a research summary?

A research summary is a piece of writing that summarizes your research on a specific topic. Its primary goal is to offer the reader a detailed overview of the study with the key findings. A research summary generally contains the article’s structure in which it is written.

You must know the goal of your analysis before you launch a project. A research overview summarizes the detailed response and highlights particular issues raised in it. Writing it might be somewhat troublesome. To write a good overview, you want to start with a structure in mind. Read on for our guide.

Why is an analysis recap so important?

Your summary or analysis is going to tell readers everything about your research project. This is the critical piece that your stakeholders will read to identify your findings and valuable insights. Having a good and concise research summary that presents facts and comes with no research biases is the critical deliverable of any research project.

We’ve put together a cheat sheet to help you write a good research summary below.

Research Summary Guide

• Why was this research done?  – You want to give a clear description of why this research study was done. What hypothesis was being tested?
• Who was surveyed? – The what and why or your research decides who you’re going to interview/survey. Your research summary has a detailed note on who participated in the study and why they were selected. 
• What was the methodology? – Talk about the methodology. Did you do face-to-face interviews? Was it a short or long survey or a focus group setting? Your research methodology is key to the results you’re going to get. 
• What were the key findings? – This can be the most critical part of the process. What did we find out after testing the hypothesis? This section, like all others, should be just facts, facts facts. You’re not sharing how you feel about the findings. Keep it bias-free.
• Conclusion – What are the conclusions that were drawn from the findings. A good example of a conclusion. Surprisingly, most people interviewed did not watch the lunar eclipse in 2022, which is unexpected given that 100% of those interviewed knew about it before it happened.
• Takeaways and action points – This is where you bring in your suggestion. Given the data you now have from the research, what are the takeaways and action points? If you’re a researcher running this research project for your company, you’ll use this part to shed light on your recommended action plans for the business.

LEARN ABOUT:   Action Research

If you’re doing any research, you will write a summary, which will be the most viewed and more important part of the project. So keep a guideline in mind before you start. Focus on the content first and then worry about the length. Use the cheat sheet/checklist in this article to organize your summary, and that’s all you need to write a great research summary!

But once your summary is ready, where is it stored? Most teams have multiple documents in their google drives, and it’s a nightmare to find projects that were done in the past. Your research data should be democratized and easy to use.

We at QuestionPro launched a research repository for research teams, and our clients love it. All your data is in one place, and everything is searchable, including your research summaries! 

Authors: Prachi, Anas

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Research Summary

A research paper analyzes a perspective or argues a point. It is an expanded essay based on your interpretation, evaluation or argument about a certain topic.

According to Sunny Empire State College , “When you write a research paper you build upon what you know about the subject and make a deliberate attempt to find out what experts know. A research paper involves surveying a field of knowledge in order to find the best possible information in that field.” Whatever type of research paper you choose to write, it should present your own ideas backed with others’ (especially experts on the field) information and data.

Every research paper has a research summary. A research summary is a brief overview of what the whole research is about. It is a professional piece of writing that describes your research to the readers. It concisely yet perfectly captures the essence of the research as a whole. You may also see What Should Be in an Executive Summary of a Report?

Fundamentals of a Research Summary

Having a good template for a research summary is nothing if you don’t know its importance and basic function. Before you start writing your research summary, you should first know its fundamentals on the areas you need to pay attention to such as its content, style and organization.

• The content of your research summary must briefly discuss the techniques and tools used in the research and the importance of the research as a whole. Explain how the research can be of benefit for the people.
• To organize your research summary, each topic must be discussed in separate paragraphs. How you came up with a factual research must be briefly explained in a separate paragraph.
• If you have a lengthy research paper, try not to write not more than 10% of the entire paper. If it’s not as lengthy, you should not write more than 300 words in your summary.

However, rules may vary according to your research professor’s standards. This is just the basic fundamentals on how to write your research summary. Also see  Thesis Outline Examples

How to Write a Research Summary

It is apparent that a research summary is a condensed version of the main idea of your research paper. Because of this, it is advised that the summary of your paper is written after you are done with your entire research. This is to ensure that all the added information in your research can be written in your summary as well and all of those that removed can be edited out. Here are a few steps on how to write a research summary:

Read your paper

It should be a fact you should know beforehand; the importance of reading your entire research paper thoroughly to write an effective research summary. Along the way, take notes of the important details and key findings that you want to highlight in your paper. This will help you organize your summary better. Remember that your research summary is a mini-paper of your study and it should contain the main ideas of your entire research.

Write a draft

For your first draft, focus on the content rather than the length of your summary. Your draft is your first outline on what to include in the final summary. Writing a draft ensures you write a clear, thorough and coherent summary of your research paper. Also see  How to Write a Rough Outline

Identify main points

Within your research paper, you must identify the major points that will encourage prospective readers to go through your research paper. These major points must thoroughly and completely explain what the paper is trying to convey.

Separate sections

Identify the differences of the main section in your paper. Write a few sentences describing the main ideas of each section. In short, you should be able to present and thoroughly describe what each main section is focused on. It should have these basic sections:

• Introduction, brief opening statement
• Purpose of the study
• Data gathering method
• Summary of findings
• Description of recommendations with actual justification.

Combine Information

All the information you have gathered must be then used to make your summary. Remember that your summary is just an overview of your research paper as a whole. It should be not be more than 10% of your whole paper. Also see  5 Summary Writing Examples and Samples

Making The First Draft

After establishing the basic way of writing a research summary, it is a must to write a first draft. It should follow the flow of the original paper. Here’s a few steps on how to make a first draft:

First, state the research question in the introduction of your summary. This holds the ground as to the summary’s direction. Provide an explanation why your research is interesting and how it can help your target recipients.

Second, state the hypothesis you wish to prove. This will help you and your readers stay grounded on the topic at hand.

Third, briefly discuss the methodology used in your research. Discuss and describe the procedure, materials, participants, design, etc. The analysis of your data must also be included. You may also see  How to Write a Successful Thesis Proposal

Fourth, describe the results and significance of your research. And lastly, briefly discuss the key implications of your research. The results and its interpretation should directly coincide with your hypothesis.

Editing your Research Summary

A research paper is a formal piece of writing. Your summary should be tailored to your expected readers. Say for example the prospective readers are your classmates, so the style of your paper should be clearly understood by them.

Eliminate wordiness. Avoid using unnecessary adjectives and adverbs. Write in a way it would be easier for your readers to understand. It is common for research papers to establish a word count. Avoid elongating your sentences when it has shorter versions.

Being vague in describing and explaining the points of your paper might lead to confusion in your readers part. Use specific, concrete language when presenting results. Use reliable and specific examples and references as well. You should also use scientifically accurate language to help support your claims. Avoid informal words and adjectives to describe the results of your research.

Paraphrase the information you want to include in your research paper. Direct quoting the information you have read from a different source is not oftenly used in formal writings. To give the exact credit for the information you paraphrased, follow the citation format required by your professor.

Reread your paper and let others read it as well. This way minor errors you were not able to notice can be quickly pointed out and corrected.

Research Summary Writing Tips

Your research summary should not be more than 10 pages long or not more than 10% of your original document. This keeps your research summary concise and compact. It should be short enough for your readers to read through but long enough for you to clearly explain your study.

Copy and paste

Avoid simply copy and pasting different parts of your paper into your summary. You should paraphrase parts that you want to include. As most research advisers read through all of your paper, it can easily be identified if you have copy-pasted parts from your research and might give you a bad grade.

Consider the readers

Although not a requirement from your professor, catering your summary to what the readers need is sometimes required. As some studies are given out to different influential people in the field, writing a summary that caters to the readers’ necessities might be required.

Research Article Summary Template

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Research Summary Sample

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Research Writing Summary Tips (continuation)

Clarity and organization.

One of the common mistakes in writing a research is publishing an unclear and unpolished summary. Bear in mind that your readers are likely reading about the topic of your research for the first time, avoid unclear and uncertain explanations and a disorganized summary.

Use strong and positive language

Use precise and strong words to help strengthen the foundation of your summary. Your summary should be able to stand alone despite it being a part of the research paper. Once you have convinced your readers with the recommendations regarding the topic of your paper, the readers should be able to find concrete evidence and explanations within your summary. Avoid pleas and biased statements in your summary, but make sure you are able to relay the sense of urgency for the recommendations you have given.

Divide into parts

To make things easier for you, divide your paper into different sections and headings, much like creating an outline. With this in mind, every point should be explained limited to its essence. In this way, you avoid writing too much information about your paper in your summary.

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Writing an article summary.

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When writing a summary, the goal is to compose a concise and objective overview of the original article. The summary should focus only on the article's main ideas and important details that support those ideas.

Guidelines for summarizing an article:

• State the main ideas.
• Identify the most important details that support the main ideas.
• Summarize in your own words.
• Do not copy phrases or sentences unless they are being used as direct quotations.
• Express the underlying meaning of the article, but do not critique or analyze.
• The summary should be about one third the length of the original article. 

Your summary should include:

• Give an overview of the article, including the title and the name of the author.
• Provide a thesis statement that states the main idea of the article.
• Use the body paragraphs to explain the supporting ideas of your thesis statement.
• One-paragraph summary - one sentence per supporting detail, providing 1-2 examples for each.
• Multi-paragraph summary - one paragraph per supporting detail, providing 2-3 examples for each.
• Start each paragraph with a topic sentence.
• Use transitional words and phrases to connect ideas.
• Summarize your thesis statement and the underlying meaning of the article.

 Adapted from "Guidelines for Using In-Text Citations in a Summary (or Research Paper)" by Christine Bauer-Ramazani, 2020

Additional Resources

All links open in a new window.

How to Write a Summary - Guide & Examples  (from Scribbr.com)

Writing a Summary  (from The University of Arizona Global Campus Writing Center)

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• Last Updated: Mar 15, 2024 9:32 AM
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Research Summary

Learn how to provide the key points, main findings, and any other relevant information for the research you want to summarize

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What is a Research Summary?

Have you ever found yourself drowning in a sea of research articles, struggling to make sense of it all? Well, fear not! A research summary is here to save the day. But what exactly is a research summary, and how can it help you navigate the vast ocean of information?

A research summary is a concise and informative overview of a research article, report, or thesis. It aims to provide the reader with a clear understanding of the study's purpose, methods, results, and conclusions without having to read the entire document. Think of it as a mini-version of the original work that highlights its most important aspects.

Now that we know what a research summary is let's dive into why they're so beneficial.

The Benefits of Research Summaries

Research summaries offer several advantages for both readers and writers:

Time-saving : Reading a well-written research summary can save you hours of sifting through dense academic papers. It allows you to quickly grasp the key points and decide if you want to explore the full document further.

Improved comprehension : By breaking down complex ideas into digestible chunks, research summaries make it easier for readers to understand the material. This is particularly helpful for those who are new to a topic or have limited knowledge in the field.

Enhanced communication : Research summaries enable researchers to share their findings with a wider audience, including non-experts and industry professionals. This can lead to increased collaboration and knowledge exchange across disciplines.

Better decision-making : For professionals who rely on evidence-based practices, research summaries provide an accessible way to stay informed about the latest developments in their field. This enables them to make better decisions based on up-to-date information.

With these benefits in mind, let's explore some tips for writing an effective research summary.

Tips for Writing a Great Research Summary

Creating an engaging and informative research summary doesn't have to be a daunting task. Here are some tips to help you craft the perfect summary:

Know your audience : Consider who will be reading your summary and tailor your language and content accordingly. If you're writing for a general audience, avoid jargon and technical terms. If your readers are experts in the field, focus on the most relevant and novel aspects of the research.

Be concise : A research summary should be brief yet informative. Aim to capture the essence of the study without getting bogged down in unnecessary details.

Use clear language : Write in simple, straightforward sentences that are easy to understand. Avoid flowery language or complex sentence structures that may confuse readers.

Highlight key points : Focus on the main elements of the study, such as its purpose, methods, results, and conclusions. Make sure these points stand out by using headings, bullet points, or bold text.

Stay objective : Present the information in a neutral tone and avoid expressing personal opinions or biases. Stick to the facts and let your readers draw their own conclusions.

Proofread : Before submitting your research summary, take the time to proofread it carefully for grammar, spelling, and punctuation errors. A polished summary will make a better impression on your readers.

Generate the Perfect Research Summary with Our Research Summary Generator

Now that we've covered what a research summary is, its benefits, and tips for writing one – wouldn't it be great if there was a tool that could generate a perfect research summary every single time? Well, guess what? There is!

With our Research Summary Generator, you can create an engaging and informative summary in just a few clicks. Say goodbye to hours spent poring over dense academic papers and hello to quick, easy-to-understand summaries tailored to your needs.

Give it a try today and see how our Research Summary Generator can revolutionize your research process!

Example outputs

This Research Summary Generator saves you time and effort by summarizing your research findings in a clear and concise manner, allowing you to easily communicate your results to others.

The Effects of Exercise on Mental Health

A study was conducted to investigate the effects of exercise on mental health. Participants were randomly assigned to either an exercise group or a control group. The exercise group engaged in moderate-intensity aerobic exercise for 30 minutes, three times per week for eight weeks. The results showed that the exercise group had significantly lower levels of depression and anxiety compared to the control group.

Keywords: exercise, mental health, depression, anxiety

The impact of social media on body image.

This study aimed to examine the impact of social media on body image. A sample of young adults completed surveys assessing their use of social media and their perceptions of their own body image. Results indicated that individuals who spent more time on social media reported greater dissatisfaction with their bodies. Additionally, exposure to images of thin and fit individuals on social media was associated with increased body dissatisfaction.

Keywords: social media, body image, young adults, body dissatisfaction

The benefits of meditation for stress reduction.

This meta-analysis aimed to evaluate the effectiveness of meditation for stress reduction. A total of 18 randomized controlled trials were included in the analysis. Results showed that meditation was effective in reducing perceived stress, with larger effect sizes observed for mindfulness-based interventions. Furthermore, the benefits of meditation appeared to be maintained over time.

Keywords: meditation, stress reduction, mindfulness, meta-analysis

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Frequently asked questions

• How does the Research Summary Generator work? Simply input your research findings into the generator, and it will automatically summarize them in a clear and concise manner.
• Can I customize the generated summary? Yes, you can edit the summary as needed to ensure it accurately reflects your research findings.
• Is the Research Summary Generator free to use? Yes, the generator is completely free to use with no limitations.

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An executive summary is a thorough overview of a research report or other type of document that synthesizes key points for its readers, saving them time and preparing them to understand the study's overall content. It is a separate, stand-alone document of sufficient detail and clarity to ensure that the reader can completely understand the contents of the main research study. An executive summary can be anywhere from 1-10 pages long depending on the length of the report, or it can be the summary of more than one document [e.g., papers submitted for a group project].

Bailey, Edward, P. The Plain English Approach to Business Writing . (New York: Oxford University Press, 1997), p. 73-80 Todorovic, Zelimir William and Marietta Wolczacka Frye. “Writing Effective Executive Summaries: An Interdisciplinary Examination.” In United States Association for Small Business and Entrepreneurship. Conference Proceedings . (Decatur, IL: United States Association for Small Business and Entrepreneurship, 2009): pp. 662-691.

Importance of a Good Executive Summary

Although an executive summary is similar to an abstract in that they both summarize the contents of a research study, there are several key differences. With research abstracts, the author's recommendations are rarely included, or if they are, they are implicit rather than explicit. Recommendations are generally not stated in academic abstracts because scholars operate in a discursive environment, where debates, discussions, and dialogs are meant to precede the implementation of any new research findings. The conceptual nature of much academic writing also means that recommendations arising from the findings are distributed widely and not easily or usefully encapsulated. Executive summaries are used mainly when a research study has been developed for an organizational partner, funding entity, or other external group that participated in the research . In such cases, the research report and executive summary are often written for policy makers outside of academe, while abstracts are written for the academic community. Professors, therefore, assign the writing of executive summaries so students can practice synthesizing and writing about the contents of comprehensive research studies for external stakeholder groups.

When preparing to write, keep in mind that:

• An executive summary is not an abstract.
• An executive summary is not an introduction.
• An executive summary is not a preface.
• An executive summary is not a random collection of highlights.

Christensen, Jay. Executive Summaries Complete The Report. California State University Northridge; Clayton, John. "Writing an Executive Summary that Means Business." Harvard Management Communication Letter (July 2003): 2-4; Keller, Chuck. "Stay Healthy with a Winning Executive Summary." Technical Communication 41 (1994): 511-517; Murphy, Herta A., Herbert W. Hildebrandt, and Jane P. Thomas. Effective Business Communications . New York: McGraw-Hill, 1997; Vassallo, Philip. "Executive Summaries: Where Less Really is More." ETC.: A Review of General Semantics 60 (Spring 2003): 83-90 .

Structure and Writing Style

Writing an Executive Summary

Read the Entire Document This may go without saying, but it is critically important that you read the entire research study thoroughly from start to finish before you begin to write the executive summary. Take notes as you go along, highlighting important statements of fact, key findings, and recommended courses of action. This will better prepare you for how to organize and summarize the study. Remember this is not a brief abstract of 300 words or less but, essentially, a mini-paper of your paper, with a focus on recommendations.

Isolate the Major Points Within the Original Document Choose which parts of the document are the most important to those who will read it. These points must be included within the executive summary in order to provide a thorough and complete explanation of what the document is trying to convey.

Separate the Main Sections Closely examine each section of the original document and discern the main differences in each. After you have a firm understanding about what each section offers in respect to the other sections, write a few sentences for each section describing the main ideas. Although the format may vary, the main sections of an executive summary likely will include the following:

• An opening statement, with brief background information,
• The purpose of research study,
• Method of data gathering and analysis,
• Overview of findings, and,
• A description of each recommendation, accompanied by a justification. Note that the recommendations are sometimes quoted verbatim from the research study.

Combine the Information Use the information gathered to combine them into an executive summary that is no longer than 10% of the original document. Be concise! The purpose is to provide a brief explanation of the entire document with a focus on the recommendations that have emerged from your research. How you word this will likely differ depending on your audience and what they care about most. If necessary, selectively incorporate bullet points for emphasis and brevity. Re-read your Executive Summary After you've completed your executive summary, let it sit for a while before coming back to re-read it. Check to make sure that the summary will make sense as a separate document from the full research study. By taking some time before re-reading it, you allow yourself to see the summary with fresh, unbiased eyes.

Common Mistakes to Avoid

Length of the Executive Summary As a general rule, the correct length of an executive summary is that it meets the criteria of no more pages than 10% of the number of pages in the original document, with an upper limit of no more than ten pages [i.e., ten pages for a 100 page document]. This requirement keeps the document short enough to be read by your audience, but long enough to allow it to be a complete, stand-alone synopsis. Cutting and Pasting With the exception of specific recommendations made in the study, do not simply cut and paste whole sections of the original document into the executive summary. You should paraphrase information from the longer document. Avoid taking up space with excessive subtitles and lists, unless they are absolutely necessary for the reader to have a complete understanding of the original document. Consider the Audience Although unlikely to be required by your professor, there is the possibility that more than one executive summary will have to be written for a given document [e.g., one for policy-makers, one for private industry, one for philanthropists]. This may only necessitate the rewriting of the introduction and conclusion, but it could require rewriting the entire summary in order to fit the needs of the reader. If necessary, be sure to consider the types of audiences who may benefit from your study and make adjustments accordingly. Clarity in Writing One of the biggest mistakes you can make is related to the clarity of your executive summary. Always note that your audience [or audiences] are likely seeing your research study for the first time. The best way to avoid a disorganized or cluttered executive summary is to write it after the study is completed. Always follow the same strategies for proofreading that you would for any research paper. Use Strong and Positive Language Don’t weaken your executive summary with passive, imprecise language. The executive summary is a stand-alone document intended to convince the reader to make a decision concerning whether to implement the recommendations you make. Once convinced, it is assumed that the full document will provide the details needed to implement the recommendations. Although you should resist the temptation to pad your summary with pleas or biased statements, do pay particular attention to ensuring that a sense of urgency is created in the implications, recommendations, and conclusions presented in the executive summary. Be sure to target readers who are likely to implement the recommendations.

Bailey, Edward, P. The Plain English Approach to Business Writing . (New York: Oxford University Press, 1997), p. 73-80; Christensen, Jay. Executive Summaries Complete The Report. California State University Northridge; Executive Summaries. Writing@CSU. Colorado State University; Clayton, John. "Writing an Executive Summary That Means Business." Harvard Management Communication Letter , 2003; Executive Summary. University Writing Center. Texas A&M University;  Green, Duncan. Writing an Executive Summary.   Oxfam’s Research Guidelines series ; Guidelines for Writing an Executive Summary. Astia.org; Markowitz, Eric. How to Write an Executive Summary. Inc. Magazine, September, 15, 2010; Kawaski, Guy. The Art of the Executive Summary. "How to Change the World" blog; Keller, Chuck. "Stay Healthy with a Winning Executive Summary." Technical Communication 41 (1994): 511-517; The Report Abstract and Executive Summary. The Writing Lab and The OWL. Purdue University; Writing Executive Summaries. Effective Writing Center. University of Maryland; Kolin, Philip. Successful Writing at Work . 10th edition. (Boston, MA: Cengage Learning, 2013), p. 435-437; Moral, Mary. "Writing Recommendations and Executive Summaries." Keeping Good Companies 64 (June 2012): 274-278; Todorovic, Zelimir William and Marietta Wolczacka Frye. “Writing Effective Executive Summaries: An Interdisciplinary Examination.” In United States Association for Small Business and Entrepreneurship. Conference Proceedings . (Decatur, IL: United States Association for Small Business and Entrepreneurship, 2009): pp. 662-691.

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Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization

• Yue Su 1   na1 ,
• Youqian Zhang 2   na1 &
• Jinfu Xu 1  

BMC Pulmonary Medicine volume  24 , Article number:  240 ( 2024 ) Cite this article

Metrics details

Previous research has emphasized the potential benefits of anti-diabetic medications in inhibiting the exacerbation of Chronic Obstructive Pulmonary Disease (COPD), yet the role of anti-diabetic drugs on COPD risk remains uncertain.

This study employed a Mendelian randomization (MR) approach to evaluate the causal association of genetic variations related to six classes of anti-diabetic drug targets with COPD. The primary outcome for COPD was obtained from the Global Biobank Meta-analysis Initiative (GBMI) consortium, encompassing a meta-analysis of 12 cohorts with 81,568 cases and 1,310,798 controls. Summary-level data for HbA1c was derived from the UK Biobank, involving 344,182 individuals. Positive control analysis was conducted for Type 2 Diabetes Mellitus (T2DM) to validate the choice of instrumental variables. The study applied Summary-data-based MR (SMR) and two-sample MR for effect estimation and further adopted colocalization analysis to verify evidence of genetic variations.

SMR analysis revealed that elevated KCNJ11 gene expression levels in blood correlated with reduced COPD risk (OR = 0.87, 95% CI = 0.79–0.95; p  = 0.002), whereas an increase in DPP4 expression corresponded with an increased COPD incidence (OR = 1.18, 95% CI = 1.03–1.35; p  = 0.022). Additionally, the primary method within MR analysis demonstrated a positive correlation between PPARG-mediated HbA1c and both FEV1 (OR = 1.07, 95% CI = 1.02–1.13; P  = 0.013) and FEV1/FVC (OR = 1.08, 95% CI = 1.01–1.14; P  = 0.007), and a negative association between SLC5A2-mediated HbA1c and FEV1/FVC (OR = 0.86, 95% CI = 0.74–1.00; P  = 0.045). No colocalization evidence with outcome phenotypes was detected (all PP.H4 < 0.7).

This study provides suggestive evidence for anti-diabetic medications' role in improving COPD and lung function. Further updated MR analyses are warranted in the future, following the acquisition of more extensive and comprehensive data, to validate our results.

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Introduction

Chronic obstructive pulmonary disease (COPD), is a progressive lung disease characterized by poorly reversible airflow blockage and persistent lung inflammation [ 1 ], contributing to increased resistance to airflow in the small conducting airways, reduced compliance of the lungs, and progressive airflow obstruction and air trapping [ 2 ]. Owing to the lung is a complex and vulnerable organ that is exposed to smoking, environmental degradation, and occupational hazards, the prevalence rate of COPD is increasing [ 3 ]. Based on the systematic analysis for the Global Burden Disease Study 2019, lower respiratory infection was the 3rd and COPD was the 6th cause of death, and the incidence rates vary by country and region, with higher rates in low- and middle-income countries and among people who smoke or work in industries with exposure to lung irritants [ 4 ]. The treatment for COPD includes medications, oxygen therapy, pulmonary rehabilitation, surgery, and lifestyle changes.

Diabetes mellitus is a chronic and metabolic disease, involving inappropriately increased blood glucose levels and systematic inflammatory responses accompanied by decreased insulin synthesis, insulin resistance (IR) or reduced metabolic response to insulin in many tissues [ 5 ]. To date, the major classes of oral antihyperglycemic medications include biguanides (e.g., metformin), thiazolidinedione (TZD), sulfonylureas, glucagon-like peptide 1 (GLP-1) receptor agonists, Insulin/insulin analogues (i.e., INSR), sodium-glucose cotransporter (SGLT2) inhibitors, dipeptidyl peptidase-IV (DPP-IV) inhibitors, and α-glucosidase inhibitors. Several studies have demonstrated the beneficial effect of antidiabetic drugs on COPD and its exacerbations. Pradhan et al. have demonstrated that GLP-1 receptor agonists and SGLT-2 inhibitors were capable of reducing severe exacerbations compared to sulfonylureas in patients diagnosed with COPD. However, the use of DPP-4 inhibitors did not clearly show a reduced risk of exacerbations in COPD [ 6 ]. Similarly, Au et al have suggested that SGLT2 inhibitor was associated with a decreased risk of incidence and exacerbations of obstructive airway diseases (OAD) compared with DPP4 inhibitor [ 7 ]. However, Hitchings et al. have found that metformin did not effectively decrease blood glucose levels in non-diabetic patients admitted to the hospital due to exacerbations of COPD, and no beneficial effect on CRP downregulation or clinical outcomes was identified [ 8 ]. However, to date, the role of antidiabetic drugs on COPD risk is inconclusive, and the confounding bias and conflicting results contribute to uncertain causation between antihyperglycemic medications and COPD.

Mendelian randomization is a statistical technique used in epidemiology and genetics to investigate causal relationships between an exposure (or risk factor) and an outcome, utilizing genetic variants or alleles as instrumental variables to estimate the causal effect of an exposure on an outcome. Importantly, MR is able to provide evidence for causality by leveraging genetic variants as instrumental variables, which helps overcome issues such as reverse causality and confounding over traditional observational studies and randomized controlled trials over traditional observational studies and randomized controlled trials. It is also less prone to biases introduced by self-reporting or recall bias. Hence, we performed a two-sample MR analysis in this study to explore the association of antidiabetic drugs with COPD.

Materials and methods

Study design.

The foundational data for this study were procured from publicly accessible, summary-level datasets originating from Genome-Wide Association Studies (GWAS) and Expression Quantitative Trait Loci (eQTL) studies. A description of summary statistics data sources is available in Supplementary file 1 : Table S1 and Supplementary file 2 . Figure  1 displays the details of the Mendelian Randomization (MR) design. All included GWAS studies have received approval from the relevant institutional review boards. As this research involves secondary analysis of publicly available data, no additional ethical approval was required.

Flowchart of the study analysis

Selection of genetic instrumental variables

In this study, the GeneCard database ( https://www.genecards.org/ ) and drug targets used in this MR study [ 9 ], we identified the final drug targets analysed, namely TZD (i.e. PPARG), SU (i.e. KCNJ11 and ABCC8), GLP-1 analogues (i.e. GLP1R), Insulin/insulin analogues (i.e. INSR), SGLT2 inhibitor (i.e. SLC5A2), DPP-IV inhibitor (i.e. DPP4), metformin (i.e. PRKAB1, ETFDH, etc .). Owing to the controversy surrounding metformin's protein target and the largely unknown molecular basis of its physiological effects [ 10 ], we excluded metformin from further analytical consideration.

Summary-level data for eQTLs were sourced from the eQTLGen Consortium ( https://www.eqtlgen.org/ ). We pinpointed common eQTLs single-nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) over 1% [ 11 ] that demonstrated a statistically significant correlation ( p  < 5.0 × 10 −8 ) with PPARG, KCNJ11, GLP1R, INSR, SLC5A2 and DPP4 expression in blood. ABCC8 lacked significant eQTL levels and was therefore excluded. To generate genetic tools in this study, only cis eQTLs were included. These were defined as eQTLs situated within a 1 Mb range on either side of the encoding gene.

SNPs associated with HbA1c levels at genome-wide significance levels ( p  < 5.0 × 10 −8 ) were selected from the target genes (± 100 kb of gene location) for each drug, based on the methodology used in the previous study [ 12 ]. HbA1c was obtained from UKB. To maximize the strength of the instrument for each drug, SNPs used as instruments were allowed to be in low weak linkage disequilibrium (r2 < 0.30) with each other. Finally, four drug targets were included in the study (PPARG, KCNJ11, GLP1R and SLC5A2). Additionally, we employed F-statistics (F = beta²/se²; beta for the SNP-exposure association; variance (se)) to examine the presence of weak instrumental variables [ 13 ]. The higher the F-statistic, the stronger the instrumental strength indicated. It was a requirement that all included SNPs have an F-statistic greater than 10. In MR analyses, MR-Steiger filtering was utilized to enhance the robustness of our findings by excluding variants manifesting stronger associations with the outcomes than with the exposure [ 13 ].

The primary outcome was COPD, derived from the database with the largest sample size of GWAS data available, the Global Biobank Meta-analysis Initiative (GBMI).

The GBMI [ 14 ], covering GWAS meta-analyses of 12 biobanks (BioMe, BioVU, Colorado Center for Personalised Medicine, Estonian Biobank, FinnGen, Generation Scotland, HUNT, Lifelines, Massachusetts General Brigham Biobank FinnGen, Generation Scotland, HUNT, Lifelines, Massachusetts General Brigham Biobank, Michigan Genomics Initiative, UCLA Precision Health Biobank, UK Biobank), ultimately including a European population of 81568 cases and 1310798 controls.

For secondary outcomes, lung function traits were examined, specifically Forced Expiratory Volume in 1-second (FEV1), Forced Vital Capacity (FVC), and the FEV1/FVC ratio. We utilized data from the most extensive presently available lung function GWAS by Shrine et al., which reported 279 genome-wide significant SNPs ( p  < 5×10 −9 ) from a population of 321,407 of European ancestry [ 15 ]. The study adjusted for age, age 2 , height, and smoking status.

Statistical analyses

Primary mr analysis.

We employed the Summary-data-based Mendelian Randomization (SMR) approach to generate effect estimations using eQTLs as instrumental variables. This method enables a comprehensive exploration of the association between a specific gene's expression level and the desired outcome, utilizing summary-level data from both GWAS and eQTL studies. We used SMR software, version 1.03 ( https://cnsgenomics.com/software/smr/#Overview ), for allele harmonization and subsequent analytical procedures. The Wald ratio test was applied to individual instrumental variables (IVs), followed by the multiplicative random-effects inverse-variance-weighted (IVW) method for estimating causal associations of multiple IVs (≥ 2), supplemented by the MR-Egger and weighted median methods. The IVW weighting is directly proportional to the Wald ratio estimate for each SNP and inversely proportional to the variance estimate of the Wald ratio for each SNP. IVW provides reliable and efficient estimates when all genetic variations are considered valid. The weighted median method performs better when at least half of the genetic variations are considered invalid, whereas the MR-Egger method is applied when all genetic variations are considered invalid.

Genetic correlation analysis

Linkage Disequilibrium Score (LDSC) regression, applicable to summary-level GWAS data, serves as an effective approach to genetic correlation analysis of complex diseases or traits. It distinguishes true polygenic signals from confounding biases such as cryptic relatedness and population stratification. If the genetic correlation demonstrates both statistical and quantitative significance, the overall phenotype correlation cannot be entirely attributed to environmental confounding factors [ 16 ]. The LDSC tool ( https://github.com/bulik/ldsc ) assists us in evaluating the genetic correlations among HbA1c, COPD, FEV1, FVC, and the FEV1/FVC ratio.

Colocalization analysis

To confirm the shared causal genetic variation of eQTL implicated in the outcome phenotype as identified by MR, we conducted a colocalization analysis using the R package Coloc (version 3.2-1) [ 17 ]. The genetic variant showing the strongest association with the exposure in the MR assessment, indicated by the lowest P -value, was selected as the reference variant. Genetic variants within a range of ± 100 kb of this reference variant was included in the study. The LD reference panel was based on the 1000 Genomes v3 European ancestry dataset. The criterion for colocalization was a posterior probability exceeding 0.7 for a shared causal variant (posterior probability of hypothesis 4 > 0.7).

Sensitivity analysis

We initially conducted a positive control analysis to verify the validity of the two selected genetic instruments. As HbA1c reflects the average blood sugar level over the past 2–3 months due to long-term exposure of haemoglobin to blood sugar, we investigated the association of related exposures with HbA1c levels as a positive control study for eQTL tools. For the HbA1c GWAS tool, given that diabetes is the primary indication for hypoglycemic drugs, we conducted a positive control study by investigating the association of related exposures with T2DM.

Within the SMR analysis, we acknowledged that observed associations between gene expression and the outcome could result from a linkage scenario. To validate this, we utilized the heterogeneity in dependent instruments (HEIDI) test. A P -value less than 0.01 would indicate the possibility of an association due to linkage [ 18 ]. Considering potential horizontal pleiotropy, we initially identified other genes significantly associated with genetic IVs (5×10 −8 ) in close proximity to the top eQTL (within a 1 Mb window). We then performed SMR analysis to determine whether a single SNP was associated with the expression of multiple genes.

During the MR analysis, numerous tests were employed to ensure rigour and validity. Cochran's Q test was used to assess heterogeneity amongst the selected genetic variants, with a P -value of less than 0.05 indicating significant dissimilarity among the SNPs under investigation [ 16 ]. We further scrutinized any potential directional pleiotropy within our MR study by using MR-Egger regression [ 19 ]. Significant directional pleiotropy is indicated by a P -value less than 0.05 for the MR-Egger's intercept, despite this method's relative lack of precision [ 20 ]. We also employed the MR-PRESSO method to identify potential outliers and explore horizontal pleiotropy, inferred if the global P -value is under 0.05 [ 21 ]. This process allowed for the removal of outliers, thereby improving the accuracy of our correction. Following the Bonferroni adjustment for multiple testing, we regarded a P -value smaller than 0.0125 (derived from 0.05/4) as evidence of a statistically significant causal association. A P -value lower than 0.05 is considered to offer suggestive evidence of a possible causal relationship.

Genetic instruments selection and genetic correlation between phenotypes

We identified 1127, 330, 134, and 13 cis-eQTLs for the drug target genes PPARG, KCNJ11, GLP1R, and SLC5A2, respectively, from the eQTLGen Consortium. The most significant cis-eQTL SNP for each drug target gene was selected as a genetic tool. Furthermore, from the GWAS summary data for HbA1c levels, we identified 23, 3, 3, and 4 SNPs within or near the genes PPARG, KCNJ11, GLP1R, and SLC5A2, respectively (Supplementary file 1 : Table S2). The average F-statistic values of all instrument variations are 63.73, 81.69, 51.69, and 32.44, respectively, indicating robustness against weak instrument bias (Supplementary file 1 : Table S3). In the positive control study, significant associations were observed between exposure to each drug and HbA1c when using the IVs represented by eQTLs (Supplementary file 1 : Table S4). Similarly, significant associations were found between exposure to each medication and T2DM when using the IVs proposed by HbA1c GWAS, further confirming the effectiveness of the selected genetic instruments (Supplementary file 1 : Table S5).

LDSC analysis unveiled robust genetic correlations between HbA1c and COPD (genetic correlation = 0.2048, P  = 3.52×10 −13 ), FEV1 (genetic correlation = -0.1179, P  = 1.27×10 −7 ), and FVC (genetic correlation = -0.1342, P  = 2.88×10 −9 ). A less pronounced genetic correlation was observed between HbA1c and FEV1/FVC (genetic correlation = 0.0221, P  = 0.32). SNP-based liability-scale heritability h² for HbA1c, COPD, FEV1, FVC, and FEV1/FVC were 0.173, 0.011, 0.196, 0.191, and 0.189, respectively (Supplementary file 1 : Table S6).

Primary analysis

In Fig.  2 , the SMR analysis provided suggestive evidence that a one standard deviation (SD) increases in the blood expression of the KCNJ11 gene reduced the incidence of COPD by 13% (OR = 0.87, 95% CI = 0.79–0.95; P  = 0.002). Additionally, a one SD increase in the expression of the DPP4 gene in the blood increased the incidence of COPD by 18% (OR = 1.18, 95% CI = 1.03–1.35; P  = 0.022), implying that HMGCR agonists and DPP4 inhibitors may reduce the risk of COPD. No significant association was found between the expression of PPARG, GLP1R, INSR, and SLC5A2 and outcome phenotypes (Supplementary file 1 : Table S7).

Summary-data-based Mendelian randomization (SMR) association between expression of gene PPARG, KCNJ11, GLP lR, INSR, SLC5A2, or DPP4 and outcome phenotypes. SMR method was used to assess the association. COPD, chronic obstructive pulmonary disease; FEV 1, forced expiratory volume in 1-second;FVC, forced vital capacity; HEIDI, heterogeneity in dependent instruments.

In Fig.  3 , The MR analysis found strong evidence for an association between PPARG-mediated HbA1c and higher FEV1 (OR = 1.07, 95% CI = 1.02–1.13; P  = 0.013) as well as FEV1/FVC (OR = 1.08, 95% CI = 1.01–1.14; P  = 0.007), supporting a protective role of PPARG agonists on lung function (Fig.  2 , Table S 4 ). Suggestive evidence was observed for an association between SLC5A2-mediated HbA1c and lower FEV1/FVC (OR = 0.86, 95% CI = 0.74-1.00; P  = 0.045), supporting a protective role of SLC5A2 inhibitors on lung function. No evidence was found of an association between HbA1c mediated by KCNJ11 or GLP1R and outcome phenotypes (Supplementary file 1 : Table S8). All genes demonstrated no evidence of colocalization with the risk of outcome phenotypes (posterior probability of hypothesis 4 < 0.7) (Supplementary file 1 : Table S9 and Supplementary file 3 : Figure S1-24).

Summary results of the primary MR analyses between HbA1c mediated by gene PPARG, KCNJ11, GLP lR, or SLC5A2 and outcome phenotypes. IVW, Inverse-variance-weight; MR, Mendelian randomization; COPD, chronic obstructive pulmonary disease; FEV 1, forced expiratory volume in 1-second; FVC, forced vital capacity.

The SMR analysis revealed that all observed associations were not due to linkage disequilibrium (HEIDI test P  > 0.01), with the exception of associations between PPARG expression and FVC ( P  = 0.009), and DPP4 expression and FEV1 ( P  = 0.009) and FVC ( P  = 0.004) (Supplementary file 1 : Table S10). We further explored potential horizontal pleiotropy between KCNJ11 and DPP4 expression and COPD and lung function, by examining associations between the expression of nearby genes significantly associated with the top eQTL SNPs of KCNJ11 and DPP4 and the outcomes. We identified 4 genes (including DPP4) and 8 genes (including KCNJ11) whose expressions were associated with instrumental variants (Table S). After screening, only two and eight genes, respectively, for DPP4 and KCNJ11, had available eQTLs at the genome-wide level ( P  < 5.0 × 10 −8 ). The final results indicated that only KCNJ11 and DPP4 expression were significantly associated with COPD, ruling out the distortion of the results by horizontal pleiotropy (Supplementary file 1 : Table S11).

In MR analysis, the Cochran Q test found no heterogeneity in the main reported results (all P  > 0.05; Table S 4 ), but unremovable heterogeneity was found in the PPARG-mediated HbA1c with FEV1 and FVC, and SLC5A2-mediated HbA1c with FVC. However, the intercepts in the MR-Egger regression and MR-PRESSO analyses indicated that the overall horizontal pleiotropy was not significant. Additionally, all instrumental variables passed MR-Steiger filtering, proving that the results remain robust (all P  > 0.05; Supplementary file 1 : Table S8).

The present study demonstrated the association between antidiabetic drugs and respiratory diseases through the SMR method. We found robust genetic correlations between HbA1c and COPD and lung function, including FEV1, and FVC. Moreover, with every SD increase in the expression of the KCNJ11 gene in the blood, the incidence of COPD is reduced by 13%, implying that KCNJ11 agonists may reduce the risk of COPD. Likewise, every SD increase in the expression of the DPP4 gene in the blood, the incidence of COPD increases by 18%. No significant association was found between the expression of PPARG, GLP1R, INSR, and SLC5A2 and outcome phenotypes.

PPARG, KCNJ11, GLP1R, and SLC5A2 are common therapeutic targets of antihyperglycemic drugs which are capable of inducing cellular differentiation, reducing cellular proliferation and inducing apoptosis [ 22 ]. PPARG is a member of the nuclear receptor superfamily of ligand-dependent transcription factors that is predominantly expressed in adipose tissue, modulating insulin sensitization and glucose metabolism [ 23 ]. Moreover, PPARG also reduces the morbidity in the experimental models of asthma, COPD and acute lung injury [ 24 ,  25 ]. Specifically, Solleti and colleagues have suggested that PPARG in the airway epithelial cell is able to modulate cigarette smoke-induced chemokine expression and emphysema susceptibility in mice [ 26 ]. Similarly, Karagiannis et al have found that PPARG is capable of controlling lipid uptake and transient storage in lipid droplets by influencing glucose levels [ 27 ]. GLP-1 as an incretin hormone possesses anti-inflammatory and immune-modulatory functions, and its receptor agonists contribute to decreased blood glucose levels [ 28 ]. Available studies have suggested that GLP-1 and its based agents have therapeutic potential in lung injury and COPD [ 29 ,  30 ]. Wei et al have shown that GLP-1-based pharmaceuticals presented reduced occurrence in most chronic lung diseases, except for interstitial lung disease [ 31 ]. Dogan et al have demonstrated that liraglutide use leads to increased FVC but no benefits in FEV1/FVC and 6-min walking distance [ 32 ]. Moreover, Rogliani and colleagues have shown that FEV1, FVC and maximal expiratory flow are significantly elevated after the GLP-1R treatment but not in the control group and insulin cohorts [ 33 ]. SLC5A2, namely the SGLT2 gene, was reported to be the drug target for SGLT2 inhibitors, hence the spatial distribution of SLC5A2 would provide insights into the target tissues of SGLT2 inhibitors [ 34 ]. Takashima and colleagues have demonstrated that low-dose luseogliflozin ameliorates ischemic brain injury in mice without glucose-lowering effects [ 35 ]. Similarly, Joki et al have shown that tofogliflozin modulates pulmonary vascular remodelling in mice with left heart disease [ 36 ]. Importantly, Jeong and co-workers have suggested that empagliflozin is able to improve respiratory function, reduce ischemia/reperfusion (I/R)-induced pulmonary edema and inflammatory cytokine production and protein concentration in the bronchoalveolar lavage (BAL) fluid through ERK1/2-mediated signalling pathway [ 37 ]. However, no significant association was found between the expression of PPARG, GLP-1R, and SLC5A2 and outcome phenotypes through SMR analysis, while KCNJ11 and DPP4 inhibitors may reduce the risk of COPD.

KCNJ11 encodes pancreatic β cell KATP channel pore-forming subunit (Kir6.2) with a key role in insulin secretion and glucose homeostasis, and mutation in KCNJ11 contributes to impaired blood glucose control [ 38 ]. A national cohort study showed that SU application was related to lower risks of cardiovascular events, ventilation use, pulmonary pneumonia, and mortality in the patients with COPD and diabetes [ 39 ]. Consistently, Wang et al have suggested that a duration-dependent beneficial impact of SU on severe COPD exacerbation was proved in patients with diabetes [ 40 ]. DPP4 encodes dipeptidyl peptidase 4 expressed on most cell types to decrease the expression of GLP-1 in the intestinal tract [ 41 ]. Kotnala and colleagues have shown that alveolar macrophages isolated from COPD patients presented higher DPP4 expression than that of healthy individuals, and DPP4 inhibition may alleviate the severity of haemophilus influenzae-induced COPD [ 42 ]. Similarly, the level of serum DPP4 was elevated in the patients with acute COPD exacerbation (AECOPD) [ 43 ]. However, a clinical study by Au et al found that DPP4 inhibitor use did not reduce the OAD exacerbations [ 7 ].

MR analysis is a genetic epidemiological approach that takes advantage of minimizing bias due to confounding and reverse causality and thus improves the causal inference [ 44 ]. In the present study, we found that no significant association was found between the expression of PPARG, GLP1R, INSR, and SLC5A2 and outcome phenotypes. Two-sample MR analyses have suggested that PPARG or SLC5A2-mediated HbA1c play an important role in lung function, suggesting a protective role of SLC5A2 inhibitors on lung function. Additionally, there was no evidence of an association between HbA1c mediated by KCNJ11 or GLP1R and outcome phenotypes. In the SMR analysis, only KCNJ11 and DPP4 expression were significantly associated with COPD. However, the intercepts in the MR-Egger regression and MR-PRESSO analyses indicated that the overall horizontal pleiotropy was not significant.

The primary advantage of this study lies in employing genetic tools to represent drug exposure, a strategy that reduces potential bias from external factors and prevents the issue of reverse causation. Furthermore, we utilized two distinct genetic instruments to mimic the drug under investigation. This approach adds credibility to the obtained effect estimates as they support each other. Additionally, we conducted several sensitivity analyses to assess the reliability of the genetic instruments and the assumptions made in this study. However, there are several limitations in this study. First, while we have conducted a range of sensitivity analyses to evaluate the assumptions of the MR study, it is important to acknowledge that the possibility of confounding bias and/or horizontal pleiotropy cannot be entirely ruled out. Second, it is important to note that the anticipated effects of drugs based on genetic predictions may not align with actual therapeutic outcomes. The genetic variants that serve as instruments for drug exposure are present from birth and lasts throughout one's lifetime. Consequently, our analyses cannot capture the impact of exposure to antidiabetic medications during specific periods of life. Third, it is worth noting that the eQTLs and GWAS data utilized in our research primarily stem from individuals with European ancestry, hence, extending these findings to other population groups is essential. Lastly, due to the use of summary-level data, we were unable to conduct subgroup analyses. Therefore, it is imperative to conduct further MR studies using individual-level data to obtain more comprehensive and detailed information to decide the individuals who are likely to be taking these drugs.

To sum up, the MR analysis indicates a potential cause-and-effect connection between KCNJ11 and DPP4 inhibitors and COPD risk, recommending that clinical trials should be conducted to investigate whether antidiabetic drugs offer protective benefits against COPD. Additionally, more research is necessary to delve into the underlying mechanisms.

Availability of data and materials

The authors confirm that the data supporting the findings of this study within the article and its Supplementary material. Raw data analyzed for the present study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all GWAS participants and investigators for making the summary statistics data publicly available.

This work was sponsored by the National Natural Science Foundation of China (81925001 to Jin-Fu Xu), the Innovation Program of Shanghai Municipal Education Commission (202101070007-E00097 to Jin-Fu Xu); the Program of Shanghai Municipal Science and Technology Commission (21DZ2201800 to Jin-Fu Xu). Shanghai Pujiang Program (22PJD065 to Yue Su).

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Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, China

Yue Su & Jinfu Xu

Yangtze University, Jingzhou, Hubei Province, 434000, China

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Material preparation, data collection and analysis were performed by YS and YQZ. Paper retouching by JFX. Format modification by YS and YQZ. The first draft of the manuscript was written by YS, YQZ and all authors commented on previous versions of the manuscript. All authors reviewed the manuscript.

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Su, Y., Zhang, Y. & Xu, J. Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization. BMC Pulm Med 24 , 240 (2024). https://doi.org/10.1186/s12890-024-02959-1

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Received : 23 August 2023

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DOI : https://doi.org/10.1186/s12890-024-02959-1

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