Semaglutide and atrial fibrillation: a systematic review and meta-analysis of randomized clinical trials

Abstract Introduction Semaglutide is a glucagon-like peptide-1 receptor agonist that has been highly recommended for glycemic controland weight reduction. Obesity can also increase the risk of developing atrial fibrillation (AF). Aims To assess the association of semaglutide with cardiac arrhythmias, primarily AF. Methods We performed a systematic searched Pubmed, Embase and Cochrane database, between November and December 2023, to identify semaglutide’s randomized controlled trials (RCTs) with or without diabetic patients that reported new-onset cardiac arrythmias. A Mantel-Haenszel method and a random-effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI). Results 16 RCTs were included, 6 with oral semaglutide and 11 with subcutaneous semaglutide. A total of 19892 patients were included, providing 137 new-onset AF. Our meta-analysis revealed a lower incidence of new-onset AF in semaglutide patients (pooled odds ratio [OR], 0.54; 95% confidence interval [CI] 0.39, 0.77, P < 0.01; I2 = 0%). Sub-analysis of oral and subcutaneous showed similar significant reduction (pooled OR 0.44; 95% CI [0.22, 0.87], P = 0.02, I2 = 0% and pooled OR 0.59; 95% CI [0.39, 0.88], P < 0.01, I2 = 0%, respectively). Significant reduction was also observed, regardless diabetic status. However, semaglutide revealed similar atrial flutter incidence (pooled OR 0.78; 95% CI [0.30, 2.05], P = 0.62, I2 = 0%), ventricular arrhythmias (pooled OR 1.68; 95% CI [0.77, 3.6], P = 0.19, I2 = 0%) and sudden cardiac death (pooled OR 1.68; 95% CI [0.77, 3.66], P = 0.19, I2 = 0%). Conclusion Our study suggests that in patients with or without diabetes, semaglutide reduces the risk of new-onset atrial fibrillation. This analysis provides an additionalcardiovascular benefit of this drug besides the major adverse cardiovascular events.