Abstract
BACKGROUND: Semaglutide has demonstrated potential in controlling hyperglycemia and lowering cardiovascular (CV) risk. However, its impact on arrhythmic, major CV, and renal outcomes is not well-defined. This systematic review and meta-analysis aimed to assess these effects in patients with overweight or obesity. METHODS: We searched the PubMed, Embase, and Cochrane databases for eligible randomized controlled trials (RCTs) reported up to January 2025. We calculated overall relative risks (RRs) with 95% confidence intervals (CIs) for these outcomes. In addition, subgroup analyses were performed based on age, treatment duration and obesity level. RESULTS: Ten RCTs involving 22,937 patients were included. Compared with the controls, semaglutide significantly reduced the risk of atrial fibrillation (AF) (RR 0.79, 95% CI 0.63-0.99), sinus node dysfunction (RR 0.43, 95% CI 0.19-1.00), acute myocardial infarction (RR 0.72, 95% CI 0.60-0.85), and angina pectoris (RR 0.77, 95% CI 0.61-0.98). Subgroup analyses revealed greater efficacy in patients over 60 years old and those treated for more than 52 weeks, especially for acute myocardial infarction, angina pectoris, and acute kidney injury. CONCLUSION: Semaglutide reduces the risk of AF, sinus node dysfunction, acute myocardial infarction, and angina pectoris in patients with overweight or obesity. However, its effects on other arrhythmic, CV, and renal outcomes remain uncertain.