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

Nov 09, 2025

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Author/Summarized by Author:
Ufuk Vardar, MD
Summary Reviewer:
Fred M. Kusumoto, MD, FACC
Original Posted Date:
11/09/2025
On this page:
References
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Resources

Contribution To Literature:

The META-AF study demonstrated that adding metformin to standard care reduced atrial fibrillation (AFib) episodes in individuals with obesity or overweight despite no diagnosis of diabetes.

Study Design:

META-AF was a prospective, open-label, parallel group randomized controlled trial in which patients with paroxysmal or persistent AFib undergoing catheter ablation for AFib were randomized in a 1:1 ratio to receive metformin (n=49) (maximally tolerated dose, 1000 mg twice daily) for 12 months or standard care (n=50).

  • Total number of enrollees: 99
  • Duration of follow-up: 12 months
  • Mean patient age: 62.6 years
  • Demographics: 30.3% women; mean BMI, 32.5 kg/m2

Inclusion criteria:

  • Adults ≥18 years and BMI ≥25 kg/m2 with paroxysmal or persistent AFib undergoing AFib ablation

Exclusion criteria:

  • Diabetes mellitus
  • Current or planned antidiabetic medications
  • Glomerular filtration rate <30 mL/min/ 1.73 m2
  • Chronic metabolic acidosis or use of carbonic anhydrase inhibitors
  • Use of >2 alcoholic drinks/day on average
  • New York Heart Association class III or IV heart failure
  • Pregnancy or nursing

Other salient features/characteristics:

  • All patients were counseled for lifestyle and risk factor modification (weight loss, exercise, sleep apnea, tobacco, alcohol use)
  • No placebo was used; 12 out of 49 participants stopped taking metformin due to side effects or because they felt better or did not want to add a medication to their regimen.
  • Catheter ablation was targeting antral pulmonary vein isolation, additional ablation, and antiarrhythmic drugs per treating physician
  • Catheter ablation: 92% radiofrequency, 4% cryoballoon, 4% pulse field energy
  • AFib recurrence was checked with a hand-held electrocardiogram device (AliveCor KardiaMobile) with symptoms, weekly, or daily when notified of AFib

Principal Findings:

Primary outcome:

  • Atrial arrhythmia recurrence (>30 seconds) after a single procedure at 12 months (after a 3-month blanking period), time-to-event analysis: hazard ratio, 0.50 (95% CI, 0.2-0.9; p=0.04)

Secondary outcomes:

  • Atrial arrhythmia burden: mean of 8% in metformin plus ablation group compared with 16% in ablation alone group (p=0.02)
  • The metformin plus ablation group had fewer patients who needed a repeat ablation or cardioversion to restore normal rhythm compared with standard care (6% vs. 16%)
  • Antiarrhythmic drugs were used after ablation in 8% of patients in the metformin plus ablation group and 18% with standard care
  • Quality of life by Atrial Fibrillation Severity Scale, change in weight, change in glycated hemoglobin: significant changes in weight and glycemic control were not observed with metformin treatment compared with standard care

Safety outcomes:

  • Currently not available without the published manuscript

Interpretation:

In this open-label randomized controlled trial of patients with paroxysmal or persistent AFib, BMI ≥25 kg/m2, and without diabetes undergoing catheter ablation for AFib, metformin resulted in greater freedom from recurrent atrial arrhythmia and decreased AFib burden vs. standard care. The results suggest that metformin may lead to favorable atrial remodeling or antiarrhythmic effects independent of glycemic control in individuals with overweight or obesity.

References

Presented by Amrish Deshmukh, MD, at the American Heart Association Scientific Sessions (AHA 2025), New Orleans, LA, Nov. 9, 2025.

Resources

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: AHA Annual Scientific Sessions, AHA25, Metabolic Syndrome, Arrhythmias, Cardiac