Cardiometabolic therapy for rhythm control: A case report of refractory atrial fibrillation resolving after initiation of semaglutide for obesity

Structured abstract Background Obesity is a major modifiable risk factor for atrial fibrillation (AF) and has been linked to processes involved in atrial structural and electrical remodelling. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular events in patients with type 2 diabetes at high cardiovascular risk and are increasingly regarded as cardiometabolic therapies. Whether these agents modify the trajectory of atrial cardiomyopathy or exert direct antiarrhythmic effects beyond their metabolic actions remains an area of active investigation. Case summary A 50-year-old man with obesity (body mass index 34.9 kg/m2) and persistent AF presented with persistent symptomatic episodes despite four prior pulmonary vein isolation procedures and repeated electrical cardioversions. Rhythm monitoring was performed continuously using a wearable device since 2023, documenting recurrent episodes lasting 8–30 hours with an mEHRA class IIb–III symptom burden. Echocardiography demonstrated preserved left ventricular systolic function and left atrial enlargement. In January 2026, once-weekly subcutaneous semaglutide was initiated for weight management (0.25 mg/week with subsequent dose escalation). While a weight reduction of 14 kg was observed within six months, AF episodes and symptoms ceased immediately after treatment initiation and have not recurred during follow-up. Conclusion This case describes cessation of recurrent AF episodes following initiation of semaglutide in a patient with obesity and prior ablation failure. Potential mechanisms may include cardiometabolic effects as well as direct myocardial effects on sodium and calcium handling that have been described experimentally. Although a causal relationship cannot be established from a single observation, this finding may serve as a hypothesis-generating signal and provide a rationale for prospective studies evaluating cardiometabolic therapies as potential adjuncts in rhythm control strategies.