Glucagon-Like Peptide-1 Receptor Agonists and Risk of Arrhythmias: A Network Meta-Analysis

Arrhythmias are often associated with comorbidities such as diabetes and obesity, which significantly influence their onset and progression. In this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have garnered attention for their potential benefits, with emerging evidence indicating that GLP-1 receptor activation might offer antiarrhythmic effects. This study aimed to evaluate the impact of all GLP-1 RAs and co-agonists on the incidence of new-onset arrhythmias, particularly atrial fibrillation (AF). A comprehensive search of databases was conducted from inception to December 2025. Eligible studies included randomized controlled trials (RCTs) focusing on patients with diabetes or obesity receiving GLP-1 RAs or co-agonists. Risk ratios (RR) with 95% confidence intervals (CIs) were estimated. Interventions were ranked using the p-score cumulative rank, ranging from 0 (worst) to 1 (best). A total of 94 RCTs involving 155,989 patients were included, comparing 12 GLP-1 RAs and co-agonists. Subcutaneous semaglutide emerged as the most effective intervention, significantly reducing AF incidence compared with placebo (RR 0.82; 95% CI: 0.68 to 0.99), and compared with tirzepatide (RR 0.57; 95% CI: 0.37 to 0.88). In contrast, dulaglutide was associated with an increased risk of AF, while lixisenatide was associated with a decreased risk in atrioventricular blocks. For AF, semaglutide presented a p-score of 0.7885, while tirzepatide and dulaglutide scored 0.1830 and 0.1750, respectively. Among GLP-1 RAs and co-agonists, subcutaneous semaglutide is highlighted as the most effective intervention for reducing the risk of AF. Further studies focusing on arrhythmic outcomes are needed to confirm these findings.