New Study Finds GLP-1 Receptor Agonists May Reduce Atrial Fibrillation-Related Events in Patients with Obesity

SAN DIEGO, CA, April 25, 2025 – 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.”

Session Details

“Late Breaking Clinical Trials and Science: Clinical Trial Updates and Registries: TRANSFORM-AF: Targeting Metabolic Therapy with GLP-1 Receptor Agonism for Secondary Prevention in Atrial Fibrillation” [Friday, April 25, 2025 at 2:15 pm PT]

ⁱ Reddy V et al. Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med 2023;389:1660-1671

ⁱⁱ Sha R, Baines O, Hayes A, Tompkins K, Kalla M, Holmes AP, O’Shea C, Pavlovic D. Impact of obesity on atrial fibrillation pathogenesis and treatment options. Journal of the American Heart Association. 2024; 13(1):e032277.

ⁱⁱⁱ Hsu J et al. Initial Findings From the National Cardiovascular Data Registry of Atrial Fibrillation Ablation Procedures. J Am Coll Cardiol. 2023;81(9):867-878

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The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients and is the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal healthcare policies and standards. Incorporated in 1979 and based in Washington, D.C., it has a membership of more than 9,000 heart rhythm professionals from 94 countries. For more information, visit www.HRSonline.org.

About Heart Rhythm 2025

The Heart Rhythm Society’s annual Heart Rhythm meeting convenes 9,500 of the world’s finest clinicians, scientists, researchers, and innovators in cardiac pacing and electrophysiology. More than 2,000 international experts in the field will serve as faculty for the 200+ educational sessions, forums, symposia, and ceremonies, while 110+ exhibitors will showcase innovative products and services. For more information, visit www.HeartRhythm.com.