Effect of glucagon-like peptide-1 receptor agonists on major adverse cardiovascular events in adults with type 2 diabetes and established atherosclerotic cardiovascular disease: systematic review and meta-analysis of randomised trials.

Abstract

Cardiovascular outcome trials suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events in individuals with type 2 diabetes (T2DM), but the magnitude of benefit, including recent evidence from the landmark SOUL trial and oral formulations, remains uncertain. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (International Prospective Register of Systematic Reviews ID: CRD420251034652), searching PubMed, Embase, Cochrane CENTRAL, Scopus and ClinicalTrials.gov on 6 May 2025 for randomised controlled trials comparing GLP-1RAs with placebo or usual care in adults with T2DM and established atherosclerotic cardiovascular disease. Seven trials, including 56 191 participants (mean follow-up: 3.5 years), were analysed. GLP-1RAs reduced major adverse cardiovascular events by 11% [hazard ratio: 0.89, 95% confidence interval (CI): 0.83-0.96], all-cause mortality by 11% (hazard ratio: 0.89, 95% CI: 0.82-0.97) and hospitalisation for heart failure by 7% (hazard ratio: 0.93, 95% CI: 0.89-0.98), all with high-certainty evidence. Overall, GLP-1RAs - available in subcutaneous and oral formulations - provide clinically meaningful cardiovascular benefits in high-risk adults with T2DM.