Abstract
BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in managing hyperglycemia and reducing cardiovascular (CV) outcomes. However, its effects on arrhythmic, major CV, and microvascular outcomes remain uncertain. This systematic review and meta-analysis aimed to evaluate these outcomes in patients with type 2 diabetes (T2D) treated with semaglutide. METHODS: We searched the PubMed, Embase, and Cochrane databases for eligible randomized controlled trials (RCTs) reported up to November 2024. We performed a meta-analysis via a random-effects model to estimate overall relative risks (RRs) with 95% confidence intervals (CIs) for arrhythmic, major CV, and microvascular outcomes. We conducted subgroup analyses on the basis of different administration types, treatment comparisons, and treatment durations. Additionally, we performed a meta-regression for retinopathy complications on the basis of baseline patient characteristics. RESULTS: This meta-analysis included 30 RCTs encompassing 32490 patients with T2D. Compared with the controls, semaglutide significantly reduced the incidence of atrial fibrillation (AF) (RR 0.73, 95% CI 0.54 to 0.98), complete atrioventricular (AV) block (RR 0.22, 95% CI 0.06 to 0.80), death from CV causes (RR 0.76, 95% CI 0.58 to 0.98), and revascularization (RR 0.68, 95% CI 0.52 to 0.88). Subgroup analyses revealed that semaglutide (long-term treatment) reduced the risk of AF, supraventricular tachycardia, and complete AV block. Meta-regression analysis revealed that the heterogeneity of retinopathy complications was not associated with baseline patient characteristics. CONCLUSION: Semaglutide reduces the risk of AF, complete AV block, death from CV causes, and revascularization in patients with T2D, with long-term treatment showing greater benefits for arrhythmic outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024618146.