Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis
Pooled result · MACE, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal strokeResult — go to the resultOdds ratio 0.87 95% CI 0.81–0.93Authors' conclusion
GLP-1 RAs significantly reduce MACE, cardiovascular death, and all-cause mortality in T2D patients. Higher baseline BMI and older age were associated with greater cardiovascular benefit.
Study context
- Population
- Patients with type 2 diabetes (T2D) in cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs with placebo
- Participants
- 67,769 patients10 trials34,536 receiving GLP-1 RAs
- Comparison
- GLP-1 RAs with placebo in T2D patients
- GLP-1 RAsn = 34,536
- Outcome
- Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke
Methodological detailsrandom-effects model, meta-regression, sensitivity analyses, GRADE assessments
- Random-effects model
- Meta-regression
- Sensitivity analyses
- GRADE assessments
Pooled result
As reported in the abstract
Odds ratio
0.87
95% CI 0.81–0.93
P < 0.001
GLP-1 RAsvs placebo
OR 0.87 (95% CI 0.81–0.93); P < 0.001
Further pooled results
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Cardiovascular deathI² = 22.6% | 0.86 (0.79–0.94) | P < 0.001 | |
| All-cause mortalityI² = 17.7% | 0.87 (0.82–0.94) | P < 0.001 | |
| 0.512Odds ratio (log scale) |
Meta-regression of cardiovascular benefit by baseline covariates
- Higher baseline body mass index (BMI), logOR per kg/m²
- −0.098
- Older age, logOR per year
- −0.033
- BMI: P = 0.006, R² = 99.98%
- Age: P = 0.023, R² = 75.47%
- Greater cardiovascular benefit with higher BMI and older age
Sensitivity analyses
- Robust findings, consistent effect sizes, no single trial unduly influencing the results
GRADE certainty of evidence
- High for all outcomes
Original publication
Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. Published 31 August 2025. doi:10.
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