Richard Mark Kirkner
November 11, 2025
NEW ORLEANS — The long-approved antidiabetes therapy metformin may hold promise for reducing the burden of recurrent atrial arrhythmia after catheter ablation in people with overweight or obesity, according to new data.
George Schwartz, MD, PhD“Can an old dog learn new tricks? I think we need to stay tuned, but we certainly should pay attention,” George Schwartz, MD, PhD, cardiologist at the University of Colorado Anschutz and chief of cardiology at the Rocky Mountain Regional Veterans Affairs Medical Center in Aurora, Colorado, said after results from the META-AF trial were presented at the American Heart Association (AHA) Scientific Sessions 2025.
Trial investigator Amrish Deshmukh, MD, of the University of Michigan Health in Ann Arbor, Michigan, reported that patients enrolled in META-AF who took metformin before and after catheter ablation had about half the incidence of recurrent atrial arrhythmias lasting 30 seconds or longer a year after the procedure.
“We saw a lower rate of recurrent atrial fibrillation in patients with metformin as compared to catheter ablation alone, with 78% of patients free from recurrent atrial fibrillation or atrial arrhythmia, as compared with 58% of those in the control arm,” said Deshmukh, who presented the data.
META-AF was a randomized, open-label trial that enrolled overweight or obese individuals who did not have diabetes.
Amrish Deshmukh, MD“Metformin was well-tolerated by a majority of patients, and we did not see large weight or glycemic changes to explain the effect we saw,” Deshmukh told attendees.
He acknowledged that the study population was small, with 49 in the metformin group and 50 in the usual care group, which did not receive metformin after catheter ablation. Patients who took metformin were started on the drug up to 6 weeks before their procedure, were titrated to the maximum tolerated dose, and continued on the drug for 1 year.
Study participants were given handheld ECG monitors and had the standard clinical follow-up to monitor for arrhythmias. The study population was almost evenly divided between those with paroxysmal and persistent atrial fibrillation.
The study’s secondary outcomes included atrial fibrillation burden — that is, the percentage of days monitored with atrial fibrillation — which was 8% in the metformin group vs 16% in the ablation-only group (P = .02), Deshmukh said.
However, he noted the differences in weight and A1c between the two groups were not statistically significant, although the metformin group lost an average of 6 kg and the ablation-only group lost 2 kg. Likewise, Atrial Fibrillation Severity Scale scores were similar between the two groups, Deshmukh added.
“These differences should be interpreted in the context of anti-arrhythmic medication use or repeat ablation or cardioversion after ablation,” he said. “These were higher in the control arm in both groups; however, the differences were not statistically significant.”
At 1 year, 12 patients in the metformin group had discontinued the drug, some of whom did so not because they could not tolerate the drug but because they no longer had symptoms and decided on their own to stop taking metformin, Deshmukh said.
Metformin in the Era of Newer Drugs
Despite the emergence of GLP-1 receptor agonists and SGLT2 inhibitors to treat obesity and potentially cardiovascular disease, Schwartz told Medscape Medical News there is a place for investigating new indications for metformin for heart disease.
“The principal mechanism of action of metformin, activation of AMP [adenosine monophosphate] kinase, is thought to be a very important one,” he said, noting that experimental and observational studies have suggested metformin has an anti-arrhythmic effect in people who don’t have diabetes. He called AMP kinase a “ubiquitous, self-protection, self-survival pathway.”
He also noted that metformin is much cheaper than GLP-1 receptor agonists and SGLT2 inhibitors.
The percentage of patients in META-AF who stopped taking metformin, about 25%, is much higher than other reports, but that carries a lesson for future research, Schwartz said.
“When you try to repurpose an approved drug for a new use, the acceptance of that drug may be less in a research context or in a clinical context because patients don’t have the proven reasons to stick with the therapy,” he said.
Future studies could use a “run-in” period of low-dose metformin to weed out people who cannot tolerate the drug, he added.
Even with the “many caveats” of the study, such as its open-label design and the high dropout rate of metformin users, there still appeared to be a benefit in an intention-to-treat analysis, according to Schwartz.
“I definitely think it’s worth looking at the old dog to see if it can learn new tricks,” he said.
Deshmukh reported having no relevant financial relationships. Schwartz reported receiving research support through his institution from AstraZeneca, Sanofi, and Silence Therapeutics.
Richard Mark Kirkner is a medical journalist based in Philadelphia.
