Reduction of New Onset of Atrial Fibrillation in Patients Treated with Semaglutide: An updated systematic review and meta regression analysis of randomized controlled trials

Abstract Aim This meta-analysis aims to evaluate the effect of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RAs), on new-onset atrial fibrillation (AF) in randomized clinical trials (RCTs). Methods and Results Twenty-six RCTs involving 48,583 participants (of whom 25,879 on semaglutide) with 541 new onset AF were analyzed. Semaglutide treatment resulted in a 17% reduction in AF incidence compared to controls (OR 0.83, 95% CI 0.70–0.98, p = 0.03) with no heterogeneity (I² = 0%). The effect was more pronounced with the oral formulation, which reduced AF incidence by 52% (OR 0.48, 95% CI 0.24–0.95, p = 0.04), while studies with active comparators showed a 59% reduction in AF risk (OR 0.41, 95% CI 0.20–0.83, p = 0.01). In trials without Sodium-Glucose Co-Transporter 2 inhibitors (SGLT2i) concomitant therapy, there was a significant reduction of 21% in new-onset AF (OR 0.79, 95% CI, 0.63-0.99; p=0.04). Meta-regression revealed no influence of baseline covariates, including BMI and HbA1c. An additional meta-regression analysis evaluating the percentage of patients on SGLT2 inhibitors as a potential moderator revealed no statistically significant association (p= 0.336). Conclusions Treatment with semaglutide significantly reduces the incidence of new-onset AF. This effect appears more evident with the oral formulation and independent of baseline characteristics.