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
- Design
- Meta-analysis · 37348 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with obesity/overweight.
- Could weight loss explain it?
- PossiblyParticipants had overweight or obesity without diabetes; the abstract does not separate direct drug effects from weight loss.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In 29 trials of adults with overweight or obesity and no diabetes, GLP-1-based drugs lowered major cardiovascular events (RR 0.80), heart attacks (0.72) and all-cause death (0.81), but not cardiovascular death or stroke. They also improved some cardiometabolic measures such as blood pressure, BMI, lipids and C-reactive protein. Review rated critically low confidence (AMSTAR 2).
What the study reported
- Drugs
- Semaglutide, Tirzepatide, Retatrutide
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- excluded (no diabetes)
- Cvd status
- not an entry criterion (mixed; includes SELECT, which required established CVD)
- Sample size
- 37348
Study quality details
- Study design
- Meta-analysis
- Sample size
- 37348
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% confidence interval [CI]: [0
- Risk of bias
- not assessed (auto)
- Peer review status
- yes
How far the review's own results can be trusted
This record is a systematic review, so it is appraised with AMSTAR 2, which rates how far the review's own pooled results can be trusted. It does not grade the trials inside the review; those are appraised one by one.
On this scale High is the best rating. The levels run High, Moderate, Low, Critically low: Critically low confidence in the review is the worst rating a review can receive, and means it should not be relied on for an accurate summary. That is the opposite direction to the risk-of-bias scale used for single trials, where High is the worst.
Critically low confidence in the review · AMSTAR 2 · AI: two passes agreed (item splits settled by owner ruling)
Why: 6 critical items fail: review methods set out in a protocol before the review began; comprehensive literature search; list of excluded studies, with reasons; appropriate methods for combining results; risk of bias taken into account when interpreting the results; publication bias investigated and its likely impact discussed.
What it is used for here: Used only to find trials. A review at this level does not supply a pooled result to any outcome in this collection; the trials it lists are appraised on their own.
| Item | Answer |
|---|---|
| 1 Research question and inclusion criteria include the PICO components | Yes |
| 2 · critical Review methods set out in a protocol before the review began | No — a critical flaw |
| 3 Choice of included study designs explained | No |
| 4 · critical Comprehensive literature search | No — a critical flaw |
| 5 Study selection done by two reviewers independently | Yes |
| 6 Data extraction done by two reviewers independently | Yes |
| 7 · critical List of excluded studies, with reasons | No — a critical flaw |
| 8 Included studies described in adequate detail | Partial Yes |
| 9 · critical Satisfactory technique for assessing risk of bias in the included studies | Yes |
| 10 Funding of the included studies reported | No |
| 11 · critical Appropriate methods for combining results | No — a critical flaw |
| 12 Effect of risk of bias on the pooled results assessed | No |
| 13 · critical Risk of bias taken into account when interpreting the results | No — a critical flaw |
| 14 Differences between study results explained and discussed | Yes |
| 15 · critical Publication bias investigated and its likely impact discussed | No — a critical flaw |
| 16 Review authors' conflicts of interest and funding reported | Yes |
Where the two reviewers differed: item 3 (choice of included study designs explained): one read Yes, the other No; settled at No by a recorded ruling; item 9 (satisfactory technique for assessing risk of bias in the included studies): one read Partial Yes, the other Yes; settled at Yes by a recorded ruling; item 11 (appropriate methods for combining results): one read No, the other Yes; settled at No by a recorded ruling.
Two reviewers assessed the review independently against a written guide (AMSTAR 2 guide, version 1.1), from the full text and retrieved supplements, 2026-10-05.
Funding and conflicts
- Funding
- National Natural Science Foundation of China; Innovative Research Team of High Level Local Universities in Shanghai; Science and Technology Commission of Shanghai Municipality; Shanghai Municipal Health Commission; National Key Research and Development Program of China; Natural Science Foundation of Shanghai
- Industry funded
- No
- Manufacturer
- None identified
- Sponsor role
- no manufacturer funding identified
- Author conflicts
- The authors declare no conflicts of interest.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
The source, as retrieved
Abstract
[BACKGROUND] The 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. [METHODS] A 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. [RESULTS] A 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. [CONCLUSIONS] In 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.