GLP-1-based therapies for reduction of heart failure and cardiovascular outcomes: A systematic review and meta-analysis of randomized controlled trials

Background: Glucagon-like peptide-1 (GLP-1) based therapies have demonstrated cardiovascular benefits beyond glycemic control in patients with type 2 diabetes mellitus (T2DM). However, the magnitude and consistency of their effects across individual cardiovascular and heart failure outcomes remain incompletely defined. This systematic review and meta-analysis evaluated the effects of GLP-1-based therapies on cardiovascular mortality, hospitalization for heart failure, hospitalization for unstable angina, nonfatal myocardial infarction (MI), and nonfatal stroke. Methods: We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials evaluating GLP-1-based therapies in adults with or without T2DM. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were performed to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for each prespecified outcome. Results: Eleven randomized controlled trials comprising 81,948 participants were included, and all studies were judged to be at low risk of bias. GLP-1-based therapy significantly reduced cardiovascular mortality (RR: 0.85, 95% CI: 0.79–0.91), hospitalization for heart failure (RR: 0.90, 95% CI: 0.83–0.97), nonfatal MI (RR: 0.87, 95% CI: 0.79–0.96), and nonfatal stroke (RR: 0.88, 95% CI: 0.81–0.97). GLP-1-based therapy was not associated with a statistically significant reduction in unstable angina compared with placebo. However, substantial between-study heterogeneity was observed, indicating variability in the reported treatment effects. Heterogeneity was low for most outcomes, although moderate heterogeneity was observed for nonfatal MI ( I ² = 56%) and substantial heterogeneity for hospitalization for unstable angina ( I ² = 83%). For nonfatal MI, formal analyses showed no evidence of small-study effects. Conclusion: GLP-1-based therapies were associated with significant reductions in cardiovascular mortality, nonfatal MI, nonfatal stroke, and hospitalization for heart failure. These findings support the cardiovascular benefits of GLP-1-based therapies in patients with T2DM and elevated cardiovascular risk, while no significant benefit was observed for hospitalization because of unstable angina.