Preliminary findings presented at the American Heart Association (AHA) Scientific Sessions 2024 revealed that treatment with metformin, a common type 2 diabetes medication, lifestyle changes, or a combination of both did not significantly reduce atrial fibrillation (AFib) burden or progression compared with standard care.1
Metformin and lifestyle changes show no significant impact on atrial fibrillation (AFib) burden or progression compared with standard care. | Image credit: ibreakstock – stock.adobe.com
“Interventions including weight loss, exercise and metformin act on an enzyme called AMP kinase, which is the master regulator of metabolic stress in the cells,“ said lead study author Mina K. Chung, MD, FAHA, a cardiologist and professor of medicine at the Cleveland Clinic in Ohio, in a statement. “In this study, we examined whether interventions including these might reduce AFib burden or progression.”
Metformin works by reducing glucose production in the liver, helping regulate blood sugar levels effectively. AFib, the most common type of arrhythmia, poses significant health risks, including stroke, heart failure, and other cardiovascular complications. Over 12 million people in the US are expected to be living with AFib by 2030, underscoring the urgent need for effective prevention and management strategies, according to the AHA’s 2024 Heart Disease and Stroke Statistics.
The TRIM-AF (NCT03603912) trial included 149 adults with AFib, who were randomly assigned to 1 of 4 treatment groups: standard care (educational pamphlets on diet and exercise without personalized counseling), metformin only, a lifestyle and risk factor modification program (including referrals for diet, nutrition, exercise counseling, and management of cardiovascular risk factors), or a combination of metformin and the lifestyle program.
Participants in the lifestyle groups received diet and exercise counseling every 3 months in the first year and every 6 months in the second year. While weight loss was observed in all groups except standard care by the 1-year mark, none met activity or fitness targets.
This open-label study followed participants for up to 2 years, utilizing implanted cardiac devices to track daily AFib burden—the percentage of time participants experienced arrhythmia each day.
After 1 year, the findings showed that AFib burden decreased over time in the standard care, lifestyle and risk factor modification, and combined lifestyle and risk factor modification with metformin groups, while the metformin-only group initially showed a worsening trend before stabilizing.
However, no significant differences in AFib burden changes were observed between the 4 groups. Despite weight loss in all intervention groups—averaging 2.4% in the metformin group, 2.1% in the lifestyle group, and 4.4% in the combined group—none met the study’s target of 10% weight loss or fitness improvement goals. Device-recorded activity and exercise test results also showed no significant fitness changes.
Additionally, gastrointestinal adverse effects led over one-third of participants in the metformin groups to stop or avoid the medication. Notably, lifestyle modification groups reported improved AFib symptom scores, highlighting potential benefits for symptom relief through exercise and weight loss, even if these strategies did not reduce AFib burden.
However, the study faced several limitations. First, its small sample size reduced its statistical power. Moreover, the onset of the COVID-19 pandemic during the study further complicated recruitment efforts and disrupted in-person visits. To address these challenges, the study’s protocol was adapted to include virtual visits and reduced the target sample size from 200 to 150 participants. Despite these adjustments, the disruptions may have impacted the consistency of interventions.
“We can’t at this time recommend metformin alone as an upstream therapy for AFib, but there may be synergistic benefits to the combined arm, and that the combined arm seemed to produce some benefits, but we also have long-term results at 2 years expected,” said Chung.
The study’s 2-year follow-up is expected to conclude in fall 2025, potentially offering additional insights.
References
1. Lifestyle & risk factor changes improved AFib symptoms, not burden, over standard care. American Heart Association. News release. November 18, 2024. Accessed December 5, 2024. https://newsroom.heart.org/news/lifestyle-risk-factor-changes-improved-afib-symptoms-not-burden-over-standard-care#:~:text=A%20clinical%20trial%20with%20adults,followed%20a%20lifestyle%2Frisk%20factor.