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Study · Systematic review · 2025

14 results

Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Yin Y, Zhang M, Cao Q, Lin L, Lu J, Bi Y, Chen Y

Journal of diabetes1 Apr 2025Cited by 17 (Europe PMC)

PMID40207414 (opens in a new tab)PMCIDPMC11982705 (opens in a new tab)DOI10.1111/1753-0407.70082 (opens in a new tab)PepBankPUB-40207414
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Summary

BackgroundThe cardioprotective effects of glucagon-like peptide-1 receptor agonist (GLP-1RA)-based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta-analysis evaluates their impact on cardiovascular events and metabolic parameters in this population.MethodsA meta-analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases from inception to June 18, 2024. Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity. These studies compared GLP-1RA-based therapies with placebo and reported cardiovascular events and metabolic parameters.ResultsA total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included. Compared to placebo, GLP-1RA-based therapies significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87]), major adverse cardiovascular events (0.80, [0.72, 0.89]), myocardial infarction (0.72, [0.61, 0.85]), and all-cause mortality (0.81, [0.71, 0.93]). No significant differences were observed in cardiovascular death or stroke. Additionally, GLP-1RA-based therapies were associated with significant reductions in some cardiometabolic parameters. Among GLP-1RA-based therapies, orfroglipron demonstrated strong benefits in reducing systolic blood pressure (mean difference: -7.10 mmHg, 95% CI: [-11.00, -2.70]). Tirzepatide induced the greatest reduction in body mass index (-6.50 kg/m2, [-7.90, -5.10]) and hemoglobin A1c concentrations (-0.39%, [-0.52, -0.26]). Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C-reactive protein levels (-1.20 mg/dL, [-1.80, -0.63]), respectively.ConclusionsIn nondiabetic individuals with overweight or obesity, GLP-1RA-based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP-1RA-based therapies targeting cardiovascular risk factors.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In a meta-analysis of placebo-controlled RCTs in nondiabetic adults with overweight or obesity, retatrutide was the most effective of the GLP-1RA-based therapies at improving lipid profiles.

    In plain wordsIn a pooled analysis of trials in adults with overweight or obesity without diabetes, retatrutide was most effective of the drugs for improving blood lipids.

    Peptide
    Retatrutide
    Outcome
    Direction not reportedLipid profile improvement
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Lipids · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C-reactive protein levels (-1.20 mg/dL, [-1.80, -0.63]), respectively.
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    These studies compared GLP-1RA-based therapies with placebo and reported cardiovascular events and metabolic parameters.
  2. 02HumanSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, tirzepatide gave the greatest BMI reduction among the GLP-1RA-based therapies versus placebo (-6.50 kg/m2).

    In plain wordsIn adults with overweight or obesity and no diabetes, tirzepatide lowered BMI the most of the drugs compared, versus placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody mass index change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    BMI difference
    −6.5 kg/m2
    tirzepatide versus placebo

    Source sentences

    Summary
    Tirzepatide induced the greatest reduction in body mass index (-6.50 kg/m2, [-7.90, -5.10]
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.
  3. 03HumanSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, tirzepatide gave the greatest HbA1c reduction among the GLP-1RA-based therapies versus placebo (-0.39%).

    In plain wordsIn adults with overweight or obesity and no diabetes, tirzepatide lowered HbA1c the most of the drugs compared, versus placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    HbA1c difference
    −0.39%
    tirzepatide versus placebo

    Source sentences

    Summary
    hemoglobin A1c concentrations (-0.39%, [-0.52, -0.26]).
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.
  4. 04HumanSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, semaglutide was the most effective GLP-1RA-based therapy at reducing C-reactive protein (-1.20 mg/dL) versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, semaglutide was the best of the drugs compared at lowering the inflammation marker CRP, versus placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseC-reactive protein change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Measurements

    CRP difference
    −1.2 mg/dL
    semaglutide versus placebo

    Source sentences

    Summary
    Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C-reactive protein levels (-1.20 mg/dL, [-1.80, -0.63]), respectively.
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

Studies that did not test the peptide alone10

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

  1. 05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including semaglutide) reduced the risk of total cardiovascular events versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including semaglutide, lowered heart and blood vessel events compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseTotal cardiovascular events
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    relative risk
    0.81 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87])
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  2. 06HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including tirzepatide) reduced the risk of total cardiovascular events versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including tirzepatide, lowered heart and blood vessel events compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseTotal cardiovascular events
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    relative risk
    0.81 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87])
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  3. 07HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including semaglutide) reduced major adverse cardiovascular events versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including semaglutide, lowered major heart events compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMajor adverse cardiovascular events
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    relative risk
    0.8 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    major adverse cardiovascular events (0.80, [0.72, 0.89])
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  4. 08HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including tirzepatide) reduced major adverse cardiovascular events versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including tirzepatide, lowered major heart events compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseMajor adverse cardiovascular events
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    relative risk
    0.8 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    major adverse cardiovascular events (0.80, [0.72, 0.89])
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  5. 09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including semaglutide) reduced myocardial infarction risk versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including semaglutide, lowered heart attack risk compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMyocardial infarction
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    relative risk
    0.72 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    myocardial infarction (0.72, [0.61, 0.85])
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  6. 10HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including tirzepatide) reduced myocardial infarction risk versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including tirzepatide, lowered heart attack risk compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseMyocardial infarction
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    relative risk
    0.72 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    myocardial infarction (0.72, [0.61, 0.85])
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  7. 11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including semaglutide) reduced all-cause mortality versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including semaglutide, lowered deaths from any cause compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseAll-cause mortality
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Mortality · Cardiovascular

    Measurements

    relative risk
    0.81 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    all-cause mortality (0.81, [0.71, 0.93]
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  8. 12HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including tirzepatide) reduced all-cause mortality versus placebo.

    In plain wordsIn adults with overweight or obesity and no diabetes, GLP-1 drugs as a group, including tirzepatide, lowered deaths from any cause compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAll-cause mortality
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Mortality · Cardiovascular

    Measurements

    relative risk
    0.81 ratio
    pooled GLP-1RA-based therapies

    Source sentences

    Summary
    all-cause mortality (0.81, [0.71, 0.93]
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

  9. 13HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including semaglutide) did not significantly change cardiovascular death or stroke versus placebo.

    In plain wordsIn adults with overweight or obesity, GLP-1 drugs as a group, including semaglutide, did not significantly change heart death or stroke versus placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeCardiovascular death and stroke
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Source sentences

    Summary
    No significant differences were observed in cardiovascular death or stroke.
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  10. 14HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    In nondiabetic adults with overweight or obesity, pooled GLP-1RA-based therapies (including tirzepatide) did not significantly change cardiovascular death or stroke versus placebo.

    In plain wordsIn adults with overweight or obesity, GLP-1 drugs as a group, including tirzepatide, did not significantly change heart death or stroke versus placebo.

    Peptide
    Tirzepatide
    Outcome
    No significant changeCardiovascular death and stroke
    Study

    n = 37,348

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Source sentences

    Summary
    No significant differences were observed in cardiovascular death or stroke.
    2 context sentences
    Summary · context
    Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity.
    Summary · context
    A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included.

    In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Versions 4 to 39Current

    28 Oct 2026, 02:04 UTC

    The same notice was added 36 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.

    Study results updated

  2. Versions 2 to 3

    9 Oct 2026, 03:07 UTC

    The same notice was added 2 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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