ESC Congress 2026 Abstract · Oct 26, 2026

Semaglutide demonstrates favorable safety profile with 43% reduction in serious adverse events in adults with established ASCVD: a systematic review and meta-analysis of randomized controlled trials

By Keswani K, Reddy M, Aslam A et al.

Background: Cardiovascular disease remains the leading cause of mortality worldwide. Semaglutide, a GLP-1 receptor agonist, has shown cardiovascular benefits, but its safety profile, including risks of various adverse events, in adults with established atherosclerotic cardiovascular disease (ASCVD) requires systematic evaluation. Purpose: To evaluate whether semaglutide alters the risk of adverse events compared to placebo in adults with established ASCVD. Methods: We conducted a systematic review and meta-analysis of four randomized controlled trials comparing semaglutide versus placebo in adults with established cardiovascular disease. Fixed-effect meta-analysis was performed for 14 safety outcomes including serious adverse events, system-specific disorders, and discontinuation rates. Heterogeneity was assessed using I² statistic. Results: Semaglutide demonstrated a favorable safety profile across multiple domains. Serious adverse events were reduced by 43% (RR 0.57, 95% CI 0.46-0.72, p<0.001). Infections or infestations decreased by 30% (RR 0.70, 95% CI 0.62-0.79, p<0.001), and cardiac disorders by 58% (RR 0.42, 95% CI 0.32-0.54, p<0.001). Gastrointestinal disorders increased by 24% (RR 1.24, 95% CI 1.02-1.49, p=0.0266). No significant differences were observed in discontinuation rates (RR 1.00, 95% CI 0.97-1.04, p=0.9688), hepatobiliary disorders (RR 1.60, 95% CI 0.32-8.08, p=0.5709), renal or urinary disorders (RR 0.97, 95% CI 0.89-1.06, p=0.5013), respiratory disorders (RR 0.62, 95% CI 0.23-1.67, p=0.3483), metabolism or nutrition disorders (RR 0.74, 95% CI 0.27-2.02, p=0.5596), injury or procedural events (RR 1.77, 95% CI 0.67-4.65, p=0.2492), neoplasms (RR 0.76, 95% CI 0.36-1.63, p=0.4852), general disorders (RR 0.38, 95% CI 0.09-1.60, p=0.1896), musculoskeletal events (RR 0.82, 95% CI 0.36-1.87, p=0.6352), or nervous system disorders (RR 1.13, 95% CI 0.55-2.31, p=0.7463). Most outcomes demonstrated low heterogeneity (I²<50%), indicating consistent effects. Conclusion: Semaglutide exhibits a favorable safety profile in adults with established ASCVD, with significant reductions in serious adverse events, infections, and cardiac disorders, despite a modest increase in gastrointestinal events. These findings support semaglutide as a safe adjunctive therapy to standard secondary prevention strategies.Graphical Summary

doi.org/10.1093/eurheartj/ehag785.4181 Open access Interventions