META-AF: Metformin as an Adjunctive Therapy to Catheter Ablation of Atrial Fibrillation

Obesity is one of the main risk factors for the development and progression of atrial fibrillation (AF). Increased body mass index (BMI) is associated with a higher risk of recurrence after ablation and failure to maintain rhythm control. Intensive lifestyle modification interventions have shown a positive impact, but complementary pharmacological strategies remain under investigation. 

The META-AF (Metformin as an Adjunctive Therapy to Catheter Ablation of Atrial Fibrillation) was a single-center, randomized, open-label, parallel-group study evaluating the role of metformin in patients with BMI ≥ 25 kg/m², without diabetes, undergoing AF ablation. All participants received counseling for lifestyle modification and risk factor control (weight, exercise, sleep apnea, smoking, and alcohol). Patients in the intervention group started metformin between 0 and 6 weeks before ablation, titrated up to 1000 mg twice daily. The procedure consisted of antral pulmonary vein isolation, with additional ablations performed at the electrophysiologist’s discretion. 

The primary endpoint was recurrence of atrial arrhythmia (> 30 seconds) after a single procedure, at 12 months of follow-up, considering a 3-month blanking period. Among patients treated with metformin, there was a 50% reduction in recurrence risk (HR 0.50; 95% CI 0.2–0.9; p = 0.04). When the analysis considered only a 1-month blanking period, the effect was even more pronounced (HR 0.45; p = 0.02). 

Regarding secondary outcomes, AF burden was significantly lower in the metformin group (8% vs 16%; p = 0.02), with reduced use of antiarrhythmic drugs (8% vs 18%) and lower rates of repeat ablation or cardioversion (6% vs 16%). No significant differences were observed in body weight, HbA1c, or AF severity score (AFSS). Treatment was well tolerated, with no relevant discontinuations. 

The authors emphasized that this was a single-center, open-label study with a limited sample size, which restricts the precision of effect estimates and the evaluation of secondary endpoints. Nevertheless, the findings suggest a potential role for metformin as an adjunctive strategy to maintain sinus rhythm after ablation in overweight, non-diabetic patients, a hypothesis that warrants testing in larger, multicenter randomized trials. 

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References:  

1. Deshmukh A, Shah M M, Kozlowski P et al. Metformin as an Adjunctive Therapy to Catheter Ablation of Atrial Fibrillation (META-AF). Presented at the American Heart Association Scientific Sessions (AHA®) 2025.