Metformin Shows Promise in Reducing Atrial Fibrillation Recurrence After Catheter Ablation
核心洞察
The META-AF study found that 78% of overweight/obese adults with atrial fibrillation (搜索) who took metformin after catheter ablation remained free from AFib episodes for one year, compared to 58% in the usual care group.
Metformin treatment reduced AFib burden from 16% to 8% and decreased the need for repeat ablations or electric shock treatments from 16% to 6% compared to standard care alone.
The study included 99 adults without diabetes but with BMI ≥25 kg/m², with researchers suggesting metformin's benefits may stem from direct metabolic effects on heart cells rather than weight loss.
Adults with atrial fibrillation (搜索) and overweight or obesity (搜索) experienced significantly fewer recurrent episodes when taking metformin alongside standard care after catheter ablation, according to preliminary results from the META-AF study presented at the American Heart Association Scientific Sessions 2025.
The prospective trial analyzed 99 adults with a BMI of 25 kg/m² or higher but without a history of type 2 diabetes (搜索) who were undergoing catheter ablation for AFib. Researchers randomly assigned participants 1:1 to metformin plus ablation (n = 49; mean age, 62 years; 76% men) or usual care before ablation (n = 50; mean age, 63 years; 64% men).
Primary Outcomes Show Significant Benefit
At 12 months, the primary endpoint of freedom from recurrent AF or sustained atrial arrhythmia occurred in 38 participants in the metformin group compared to 29 participants in the usual care group (HR = 0.5; 95% CI, 0.2-0.9; P = .04). This translated to 78% of patients treated with metformin being free from recurrent atrial fibrillation (搜索) or atrial arrhythmia compared with 58% of those in the control arm.
"Treatment with metformin in people with obesity (搜索) who do not have diabetes and are undergoing AFib ablation seems to lower the likelihood of recurrent AFib or atrial arrhythmias after a single procedure," said Amrish Deshmukh, MD, clinical assistant professor of medicine at the University of Michigan in Ann Arbor and lead author of the study.
Secondary Endpoints Demonstrate Additional Benefits
The study revealed several secondary benefits of metformin treatment. The metformin group experienced a significant decrease in AFib burden, with an average of 8% compared to 16% in the ablation-alone arm. Additionally, the metformin group had fewer patients who needed a repeat ablation or electric shock to restore normal heart rhythm during an AFib episode (6% versus 16%, respectively).
Antiarrhythmia medications (搜索) were used after ablation in 8% of patients in the metformin group compared to 18% in usual care. Weight changes were minimal in all participants, consistent with prior studies of metformin use in people without diabetes.
Mechanism of Action Beyond Weight Loss
Researchers speculated about metformin's mechanism of action beyond its modest weight loss effects. "Metformin is associated with small amount of durable weight loss. Our study was not powered to detect a weight-loss difference," Deshmukh explained during a press conference. "Metformin also potentially has direct metabolic effects on cardiomyocytes (搜索) and stimulates [adenosine monophosphate] kinase, and that has been shown in basic models to be protective of atrial fibrillation (搜索)."
Study Population and Design
The study included adults with an average age of 63 years, with 70% of participants categorized as obese and the rest as overweight. Although no patients at baseline had known diabetes, about 40% had an HbA1c in the prediabetic range. Patients were equally split between paroxysmal and persistent atrial fibrillation (搜索), and 22% had undergone a previous ablation.
Researchers titrated metformin to the maximum tolerated dose, to be continued for 1 year after the ablation. Among patients in the metformin group, the median tolerated dose was 2,000 mg daily. However, 12 participants did not tolerate the drug or were not taking it 3 months after the procedure.
Tolerability and Future Directions
Drug tolerance emerged as a notable limitation, with a significant number of study participants stopping metformin due to side effects or because they felt better and didn't want to add another medication to their regimen. "The patients who are best suited for that kind of therapy are those who are, first, willing to take an additional medication," Deshmukh noted. "Then, we titrated the drug quite slowly over 6 weeks. That limited the side effects that would stop someone from continuing [therapy]."
Paul J. Wang, MD, professor of medicine and bioengineering at Stanford University, highlighted that the findings are limited by the small study size and that applicability to other technologies such as pulsed field ablation remain unknown. "This study demonstrates that metformin may be used in conjunction with AF ablation, but adoption may be limited by the generalizability and drug tolerance," Wang said.
The results raise questions about whether other medications for diabetes and weight loss, such as GLP-1 receptor agonists, may have similar benefits and side effects in adults without diabetes with AFib and obesity (搜索). Similar studies are planned or ongoing assessing the potential benefits of GLP-1 receptor agonists, including people with AF who are not undergoing an ablation.
"I would suggest conducting a larger study to investigate metformin and other diabetes treatments. We know that many of these medications offer cardiovascular benefits, and we are starting to gain a better understanding of how they might specifically benefit patients with arrhythmias," Deshmukh said.