Heart Rhythm
HRS 2026: GLP-1s tied to lower afib risk independent of weight loss
Clinical Takeaway: GLP-1 receptor agonists may lower atrial fibrillation (AF) risk and improve survival through mechanisms beyond weight loss, supporting their consideration in patients with obesity or metabolic disease at elevated AF risk.
More than 40 million people worldwide live with atrial fibrillation, and U.S. hospitalizations exceed 450,000 annually—yet traditional risk reduction strategies leave substantial residual risk.
Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with significantly lower rates of new-onset AF and improved survival, independent of weight change, according to a large retrospective study published in Heart Rhythm and presented at Heart Rhythm 2026.
Investigators analyzed 13,034 adults who initiated GLP-1 RA therapy between 2020 and 2024 and had no prior AF. Patients were identified through electronic medical records and propensity-matched 1:1 with controls drawn from over 385,000 individuals without prior GLP-1 RA use. The cohort had a mean age of 55 years, was 67% female, and had a mean baseline BMI of 35.7 kg/m².
GLP-1 RA use was associated with a striking reduction in all-cause mortality compared with controls (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.30–0.40; P<0.001). After accounting for death as a competing risk, GLP-1 RA therapy was also associated with a 25% lower risk of incident AF (HR, 0.75; 95% CI, 0.64–0.88; P<0.001).
Critically, AF risk reduction was consistent across weight-change categories. Patients who lost ≥10% of body weight saw the greatest reduction (HR, 0.42), but benefits persisted among those who lost <10% (HR, 0.78) and even those who gained weight while taking GLP-1 RAs (HR, 0.71). Semaglutide demonstrated the strongest association with AF risk reduction among agents studied.
“As atrial fibrillation continues to affect more patients worldwide, clinicians need new strategies to reduce risk and improve long-term outcomes,” said Kenneth C. Bilchick, MD, professor of cardiovascular medicine at the University of Virginia. “These findings suggest GLP-1 receptor agonists may influence heart rhythm through mechanisms beyond weight loss.”
Source: Bilchick KC, et al. (2026, April 23). Heart Rhythm. Glucagon-like peptide-1 receptor agonists reduce atrial fibrillation independently of effects on weight loss and survival