Reduction of new onset of atrial fibrillation in patients treated with semaglutide: an updated systematic review and meta regression analysis of randomized controlled trials
Arturo Cesaro, Daniele Pastori, Vincenzo Acerbo, Flavio Giuseppe Biccirè, Michele Golino, Domenico Panico, Francesco Prati, Antonio Abbate, Gregory Y.H. Lip, Paolo Calabrò
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.