Peri-ablation semaglutide exposure and atrial fibrillation recurrence: a meta-analysis of time-to-event outcomes

Background Atrial fibrillation recurrence after catheter ablation remains common, particularly in patients with obesity and metabolic comorbidity. Current atrial fibrillation management guidelines emphasize weight reduction and cardiometabolic optimization as central components of rhythm control strategies [1,2]. Semaglutide, a glucagon-like peptide-1 receptor agonist, produces substantial weight loss and improves metabolic and inflammatory profiles. Whether exposure to semaglutide around the time of ablation is associated with improved rhythm durability after atrial fibrillation ablation has not been systematically evaluated. Purpose To evaluate the association between peri-ablation semaglutide therapy and atrial arrhythmia recurrence following atrial fibrillation ablation. Methods We performed a meta-analysis of full-text studies reporting time-to-event outcomes as hazard ratios (HRs) for post-blanking atrial arrhythmia recurrence in adults undergoing ablation with peri-ablation semaglutide exposure. Log-transformed hazard ratios were pooled using inverse-variance random-effects models with restricted maximum likelihood. Prespecified sensitivity analyses included leave-one-out assessment, Hartung-Knapp adjustment and Bayesian posterior estimation using a weakly informative prior on the pooled log(HR). Results Three studies comprising metabolically enriched atrial fibrillation populations (obesity or elevated body mass index) were included. All demonstrated directionally consistent associations favoring semaglutide exposure (individual HRs 0.52, 0.68 and 0.85). The pooled random-effects estimate was HR 0.71 (95% confidence interval 0.54-0.94; p=0.015). Leave-one-out analyses showed no single-study dominance. Hartung-Knapp adjustment preserved the point estimate (HR 0.71) but widened the confidence interval (95% CI 0.39–1.29; p=0.13). Bayesian analysis yielded a posterior median HR of 0.71 (95% credible interval 0.54-0.94) with a 99.2% posterior probability of benefit (HR below 1). Conclusion In obesity-enriched atrial fibrillation populations undergoing ablation, peri-ablation semaglutide exposure was consistently associated with a lower risk of atrial arrhythmia recurrence. Although conservative adjustment attenuated frequentist significance, the magnitude and direction of association remained stable across analytic approaches. These findings support prospective randomized evaluation of semaglutide as a structured adjunct to atrial fibrillation ablation in metabolically high-risk patients.Figure 1(Bayesian): Posterior of pooled HR.