GLP-1 Therapy Linked to Lower Atrial Fibrillation and Mortality Risk-Independent of Weight Loss: Study

Use of GLP-1 medications is associated with a reduced risk of atrial fibrillation and death, and this protective effect appears independent of weight loss.

A new study, TRANSFORM-AF, found that patients with atrial fibrillation (AF) and obesity who were treated with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) experienced a reduction in AF-related events, including hospitalization, cardioversion, and ablation for AF. This multi-center pharmacoepidemiologic study, conducted across 170 Veterans Affairs hospitals, is among the first to evaluate the clinical effectiveness of GLP-1 RAs for secondary prevention of AF in patients with both obesity and pre-existing AF. Findings from the TRANSFORM-AF trial were presented today as a late-breaking clinical trial at Heart Rhythm 2025.

Despite significant advancements in modern ablation techniques, the residual risk of AF recurrence remains approximately 30% at one year and continues to rise cumulatively over time.i This persistent risk is likely driven by inadequately managed cardiometabolic risk factors, with obesity being the most prevalent.ii In the United States, over 50% of patients undergoing AF ablation are classified as obese, underscoring the need for integrated strategies that target metabolic health alongside procedural interventions.iii

The TRANSFORM-AF study aimed to evaluate whether GLP-1 RAs, typically prescribed for diabetes, could reduce the burden of AF in patients with both AF and obesity. This large, robust pharmacoepidemiologic study, involving 2,510 patients from Veterans Affairs medical centers across the United States, found that GLP-1 RA use was associated with a 13% reduction in major AF-related events, including hospitalizations for AF, cardioversions, and ablation procedures, during a median follow-up of three years. The benefits of the GLP-1 RAs were even greater for those with severe obesity (BMI over 40). Interestingly, there was only modest weight loss (an additional 4%) with diabetes management doses of GLP-1 RA, indicating a potential non-weight loss mediated effect of GLP-1 RA in AF.

"In patients with atrial fibrillation and obesity, the use of diabetic-dose GLP-1 receptor agonists was associated with improved AF-related outcomes, despite only a modest incremental weight loss," said Varun Sundaram, MD, PhD, MSc, Section Chief, Advanced Heart Failure, Louis Stokes Cleveland VA Medical Center, University Hospitals Harrington Heart &Vascular Institute, and Associate Professor of Medicine, Case Western Reserve University and Principal Investigator of the TRANSFORM-AF study.

"Given the growing obesity epidemic and the rising prevalence of atrial fibrillation, the TRANSFORM-AF study lays the foundation for a comprehensive, multimodal metabolic approach in conjunction with novel ablation techniques for patients with AF. Further randomized controlled trials are needed to assess the potential benefits of weight-loss doses of GLP-1 RA in this patient population."