Effect of glucagon-like-peptide-1 receptor agonists on major cardiovascular outcomes: a systematic review and meta-analysis

Glucagon-like-peptide-1 (GLP-1) receptor agonists are an antihyperglycemic group of drugs that have emerged as potentially preventing the risk of cardiovascular events. This meta-analysis assesses the effect of GLP-1 receptor agonists on cardiovascular outcomes. A detailed search of existing literature was based on MEDLINE, the Cochrane Library, Embase, and ClinicalTrials.gov. The search included all the studies from inception to February 2026. Statistical analyses were performed using the RevMan software, and a random-effects model was used to conduct the meta-analysis. Data were represented via forest plots, and dichotomous outcomes were evaluated using the Mantel-Haenszel method. This meta-analysis includes 12 randomized control trials (RCTs) with 82,669 patients. The analysis showed that GLP-1 receptor agonists reduce risk of cardiac death [relative risk (RR): 0.89, 95% confidence interval (CI): 0.82-0.96, p=0.003, I²=0%], all-cause mortality (RR: 0.88, 95% CI: 0.84-0.93, p<0.00001, I²=0%), stroke (RR: 0.85, 95% CI: 0.77-0.94, p=0.001, I²=0%), non-fatal stroke (RR: 0.87, 95% CI: 0.79-0.96, p=0.005, I²=0%) and revascularization (RR: 0.82, 95% CI: 0.72-0.95, p=0.007, I²=59%). There was no statistically significant reduction in myocardial infarction (MI) (RR: 0.92, 95% CI: 0.84-1.01, p=0.09, I²=42%), fatal MI (RR: 1.15, 95% CI: 0.80-1.66, p=0.44, I²=0%), non-fatal MI (RR: 0.91, 95% CI: 0.82-1.01, p=0.09, I²=51%), fatal stroke (RR: 0.75, 95% CI: 0.55-1.00, p=0.05, I²=0%), heart failure hospitalization (RR: 0.94, 95% CI: 0.85-1.03, p=0.20, I²=17%), or hospitalization for unstable angina (RR: 0.97, 95% CI: 0.85-1.12, p=0.71, I²=0%). This meta-analysis demonstrates that GLP-1 receptor agonists have a significant impact on cardiovascular death. More thorough RCTs with longer follow-up periods are required to completely understand the possible cardiovascular advantages of GLP-1 receptor agonists.