AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiometabolic Antiarrhythmic Therapy: A Systematic Review and Meta-Analysis of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Atrial and Ventricular Arrhythmias
By Sana F, pillay S, Gandhi S et al.
Introduction: Atrial and ventricular arrhythmias remain major contributors to cardiovascular morbidity and mortality despite advances in catheter ablation and device therapy. Emerging evidence suggests that GLP-1 receptor agonists and SGLT2 inhibitors exert anti-inflammatory, antifibrotic, and structural remodeling effects that may reduce arrhythmogenic burden. We performed a systematic review and meta-analysis evaluating their impact on atrial and ventricular arrhythmia outcomes. Methods: PubMed, Embase, Scopus, and Cochrane Library were systematically searched from inception through January 2026 for studies evaluating GLP-1 receptor agonists or SGLT2 inhibitors on atrial or ventricular arrhythmia outcomes. Random-effects meta-analysis pooled hazard ratios and risk ratios for atrial fibrillation, ventricular tachyarrhythmias, sudden cardiac death, and mechanistic remodeling endpoints. Results: A total of 38 studies comprising 412,684 patients were included, including 221,540 males (53.7%) and 191,144 females (46.3%), with a mean age of 64.8 ± 9.6 years. Semaglutide studies included 78,420 patients, tirzepatide 41,215, liraglutide 52,110, dapagliflozin 96,874, empagliflozin 118,640, and sotagliflozin 25,425. Hypertension was present in 72.4%, diabetes mellitus in 68.1%, obesity in 49.7%, heart failure in 38.5%, and prior atrial fibrillation in 21.3%. GLP-1 receptor agonists significantly reduced incident atrial fibrillation (RR 0.85, 95% CI 0.78-0.92; SUCRA 91.2%), while SGLT2 inhibitors reduced ventricular tachyarrhythmias and sudden cardiac death (RR 0.74, 95% CI 0.66-0.84; SUCRA 94.5%). Post-ablation atrial fibrillation recurrence was reduced with both GLP-1RA (RR 0.74, 95% CI 0.64-0.86) and SGLT2 inhibitors (RR 0.79, 95% CI 0.69-0.91). Serious adverse events were lower with SGLT2 inhibitors (OR 0.82, 95% CI 0.74-0.91) without excess treatment discontinuation. Conclusion: GLP-1 receptor agonists and SGLT2 inhibitors demonstrate significant antiarrhythmic benefits beyond metabolic control, with GLP-1RAs predominantly reducing atrial arrhythmias and SGLT2 inhibitors improving ventricular outcomes and sudden cardiac death. These findings support cardiometabolic therapy as an emerging upstream electrophysiologic strategy targeting inflammation, fibrosis, and structural remodeling across the arrhythmia spectrum.