Metformin May Be Effective Treatment for Atrial Fibrillation in Adults wtih Obesity and Without Diabetes

The oral biguanide antihyperglycemic metformin may help maintain normal sinus rhythm (NSR) after cathetr ablation in adults with atrial fibrillation (AF) and obesity, according to preliminary research presented at the American Heart Association's Scientific Sessions 2025.1 Weight loss does not appear to explain metformin's protective effect, study authors noted in a statement.2

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

The META-AF study found that 78% of participants who took metformin after ablation remained free of AF episodes lasting 30 seconds or more during the year following their procedure, compared with 58% of those who received usual care alone.1

"Lifestyle and risk factor modification efforts are essential to treating AFib and according to the results of our study could be aided by taking metformin," Amish Deshmukh, MD, lead author of the study and clinical assistant professor of medicine at the University of Michigan in Ann Arbor, said in a statement.2

The study included 99 adults with a BMI of 25 kg/m2 or higher but without a history of type 2 diabetes (T2D) who underwent catheter ablation at the University of Michigan between 2021 and 2025.1 Seventy percent of participants met criteria for obesity, while the rest were overweight. Nearly a quarter (22%) had undergone a previous ablation, and 46% had AF that stopped without treatment within a week.

Participants were randomly assigned to receive either metformin plus ablation (n = 49; mean age, 62 years; 76% men) or usual care before ablation (n = 50; mean age, 63 years; 64% men). They stratified randomization by AF type (paroxysmal vs persistent) and history of prior AF. All the participants received standard lifestyle education about physical activity, healthy eating, sleep and managing other medical conditions and were recieving anticoagulant treatment to lower stroke risk.1

Metformin doses were titrated to the maximum tolerated and continued for 1 year post-ablation. Participants were issued a handheld ECG monitor for use in addition to the ususal clinical monitoring.

After a 3-month post-ablation recovery period and dose escalation to the maximum tolerated level, participants were monitored for AF recurrence. AF burden, the percentage of monitored time spent in AF, derived from clinical and device-based data, was assessed at 3 and 12 months.1

Benefits Beyond Stable NSR

The investigators reported that the benefits observed in the metformin treatment arm extended beyond AF recurrence. These participants required fewer repeat ablations or electroconversion procedures to restore NSR during AF episodes (6%) compared with the usual care group (16%). There were also less frequent AF episodes in the intervention group during heart rhythm monitoring (8% vs 16%). Moreover, only 8% of participants who recieved metformin required antiarrhythmia medications after ablation, compared with 18% in the usual care group.1

Participants experienced only minimal weight changes, consistent with prior studies of metformin use in people without diabetes. Although potential participants wtih either type 1 or type 2 diabetes were excluded, 40% of the study population had blood glucose meeting criteria for prediabetes (HbA1c between 5.7%-6.4%).1

Medication adherence proved a challenge, according to Deshmukh et al. Of the 49 participants assigned to metformin, 12 discontinued treatment. The primary reason was occurence of adverse effects or followed by a desire to avoid additional medication despite symptom improvement.1

Larger, Comparative Study Needed

The findings raise the question of whether other glucose-lowering or weight-management agents, such as GLP-1 receptor agonists, might confer similar antiarrhythmic and metabolic benefits in adults with AF and obesity but without diabetes. “A larger, comparative study of metformin and other cardiometabolic agents could help confirm these results and clarify issues of tolerability, long-term feasibility, and cost,” Deshmukh said.2

Among the study's limitations the authors acknoweldged the small sample size, single-center design, absence of placebo control, and open-label treatment assignment, which may limit generalizability.

AF affects more than 6 million US adults and occurs more frequently in people with obesity, according to the American Heart Association's 2025 Heart Disease and Stroke Statistics.3 Previous studies in adults with diabetes and obesity showed metformin users had lower AFib risk than those taking other antidiabetic agents. Laboratory studies demonstrated metformin directly affects heart cells and reduces irregular heart rhythms.3

References

1. Deshmukh A, et al. LBS.02 Dilemmas in antithrombotic therapy in AF care post procedures. Presented at: American Heart Association Scientific Sessions; November 7-10, 2025; New Orleans. Accessed November 12, 2025.
2. Diabetes drug reduced irregular heartbeat events in overweight/obese adults with AFib. News release. American Heart Association. November 9, 2025. Accessed November 12, 2025. https://newsroom.heart.org/news/diabetes-drug-reduced-irregular-heartbeat-events-in-overweightobese-adults-with-afib
3. Martin S, Aday AW, Allen NB, et al. 2025 heart disease and stroke statisitics: a report of US and global data from the American Heart Association. Circulation. 2025;151(8). https://doi.org/10.1161/CIR.0000000000001303