BACKGROUND AND AIMS: Overweight and obesity represent major modifiable determinants of atrial fibrillation (AF) incidence and arrhythmia outcomes after AF ablation therapy. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their next-generation co-agonists exert potent weight-lowering and cardiometabolic effects and may therefore confer antiarrhythmic effects. This meta-analysis aimed to quantitatively assess the effect of GLP-1-based therapies on the risk of AF among individuals with overweight or obesity.
METHODS: A systematic search of Medline, Scopus, and the Cochrane Library was conducted for randomized controlled trials (RCTs) through October 29, 2025. Data were analyzed using random-effects pairwise meta-analysis.
RESULTS: Twenty-four RCTs encompassing 40,694 participants were included. Compared with placebo, treatment with GLP-1RAs or co-agonists resulted in a 18 % relative reduction in AF risk (Risk Ratio = 0.82; 95 % confidence interval, 0.70-0.96; P = 0.012; I = 0 %). No significant between-subgroup differences were observed according to agent type (single-, dual-, or triple-receptor agonists), individual compound, baseline BMI category (overweight/obesity vs. obesity alone), diabetes inclusion criteria, trial design [cardiovascular outcomes trial (CVOT) vs. non-CVOT], or administration route (oral vs. subcutaneous). Meta-regression analyses identified no significant effect modification by the magnitude of weight reduction or concomitant SGLT2 inhibitor use. 2
CONCLUSIONS: Among individuals with overweight or obesity, GLP-1RAs and co-agonists were associated with a lower risk of incident AF event. This cardioprotective benefit may, at least in part, operate independently of the magnitude of weight loss.
