Key result
Semaglutide cuts serious adverse events ~43% vs. placebo in established ASCVD.
Why the study?
Although semaglutide has shown cardiovascular benefits, its safety profile and risks of various adverse events in adults with established ASCVD required systematic evaluation.
Does semaglutide alter the risk of adverse events compared to placebo in adults with established ASCVD?
Meta-Analysis
Does semaglutide alter the risk of adverse events compared to placebo in adults with established ASCVD?
In adults with established ASCVD, semaglutide significantly reduces serious adverse events, infections, and cardiac disorders compared to placebo, despite a modest increase in gastrointestinal events without increasing discontinuation rates.
Supports semaglutide safety for secondary ASCVD prevention; confirms and extends RCT safety data across four trials.
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.
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Keswani et al. (2026) conducted a meta-analysis in Established atherosclerotic cardiovascular disease (ASCVD). Semaglutide vs. Placebo was evaluated on Serious adverse events (RR 0.57, 95% CI 0.46-0.72, p=<0.001). Semaglutide reduced serious adverse events by 43% compared to placebo in adults with established ASCVD (RR 0.57, 95% CI 0.46-0.72, p<0.001).
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