Key Points:
- Obesity is a well-established risk factor for atrial fibrillation (AF) and is associated with greater risk of AF progression and treatment failure.
- Observational studies have linked metformin use to lower AF incidence, but prospective randomized data in non-diabetic patients undergoing ablation are lacking.
- In the META-AF trial, metformin significantly reduced the risk of atrial arrhythmia recurrence at 12 months after ablation in patients with BMI ≥25 kg/m² and no diabetes.
- Metformin was well tolerated and associated with reduced AF burden but did not lead to significant changes in weight or glycemic control.
Obesity is a key modifiable risk factor in the management of atrial fibrillation (AF), particularly in patients undergoing catheter ablation. Although lifestyle and risk factor modification (LRFM) improves ablation outcomes, adjunct pharmacologic therapies remain underexplored—particularly in overweight or obese patients without diabetes. Observational data have suggested that metformin may reduce arrhythmia risk, prompting interest in its off-label use as an antiarrhythmic adjunct.
At the American Heart Association 2025 Scientific Sessions in New Orleans, Louisiana, USA on November 9, 2025, Dr. Amrish Deshmukh from the University of Michigan presented results from the META-AF trial, a randomized, parallel-group, open-label study evaluating the efficacy of metformin as adjunctive therapy in patients undergoing AF ablation. Eligible participants were aged ≥18 years, had a BMI ≥25 kg/m², paroxysmal or persistent AF, and no history of diabetes. A total of 99 patients were randomized to receive either catheter ablation alone or ablation plus metformin (initiated 0–6 weeks prior to ablation, titrated to 1,000 mg twice daily).
All patients received standardized counseling on lifestyle modification, including guidance on weight loss, exercise, sleep apnea management, and avoidance of tobacco and alcohol. Ablation targeted pulmonary vein isolation (PVI), with additional ablation strategies and antiarrhythmic drugs at physician discretion. Post-procedure rhythm monitoring was conducted using handheld ECGs, event monitors, and implantable devices. After a 3-month period to allow for healing after ablation and increasing metformin to the maximum dose, patients were monitored for recurrence of AFib lasting at least 30 seconds.
At 12 months, following a 3-month period, the primary endpoint; freedom from recurrent atrial arrhythmia lasting >30 seconds after a single ablation, occurred significantly more often in the metformin group (hazard ratio [HR]: 0.50; 95% CI: 0.2–0.9; p=0.04). Results remained significant in a sensitivity analysis excluding the 3-month period (HR: 0.45; p=0.02). Patients receiving metformin also had lower AF burden (8% vs. 16%; p=0.02), lower rates of antiarrhythmic drug use (8% vs. 18%), and fewer repeat ablations or cardioversions (6% vs. 16%).
No significant differences were observed in weight change or HbA1c reduction between groups. The drug was well tolerated overall, with high adherence and no major safety concerns reported. The trial was limited by its single-center design, open-label nature, and small sample size. Additionally, it was not powered to detect differences in secondary endpoints or long-term outcomes.
In discussing the implications of the study, Dr. Deshmukh remarked, “In overweight patients without diabetes, metformin appears to offer an inexpensive, well-tolerated adjunct that can improve ablation outcomes—without requiring dramatic changes in weight or glycemic control.” META-AF was supported by the Fischer Arrhythmia Fund.