GLP-1 RAs Reduce AF Risk Independent of Weight Loss Effects, With Kennith Bilchick, MD

GLP-1 medications can improve survival and decrease atrial fibrillation (AF) independent of weight loss effects, according to a recent study.1

Globally, >40 million individuals live with AF – in the US, roughly 454,000 hospitalizations are associated with AF annually. The condition also substantially increases the risk of stroke, heart failure, and various other cardiovascular complications. However, GLP-1 RAs have demonstrated significant cardioprotective effects, including in AF – although this is well-known, whether these effects are driven by weight reduction is still in question.2

“First, yes, we found that the patients who had prescriptions for these medications and took them had a reduced risk of incident atrial fibrillation,” Kenneth Bilchick, MD, professor of cardiovascular medicine at the University of Virginia and co-author of the study, told HCPLive in an exclusive interview. “Number 2 is that we found that the reduction in the risk of atrial fibrillation was additive to the effects of the drug on survival. And third, we found that the effect was also independent of weight loss.”

This single-center, retrospective study enrolled 13,034 participants in the treatment arm, all of whom were started on a GLP-1 RA between January 2020 and May 2024. Bilchick and colleagues obtained medication data via the electronic medical record and conducted propensity score matching to generate a control group matched 1:1 without replacement from a cohort of 385,723 patients without prior GLP-1 RA use or AF diagnosis. Mean age among patients in the GLP-1 RA cohort was 55 +/- 14 years and mean body mass index (BMI) was 35.7 +/- 8.7 kg/m2.1

GLP-1 RA was ultimately associated with better survival versus the control group (HR, 0.35; 95% CI, 0.3-0.4; P <.001); this survival benefit was present across all weight loss/gain and agent-specific subgroups (P <.001 for all). When accounting for competing risk of death, Bilchick and colleagues saw that GLP-1 RA use was associated with a lower risk of AF (HR, 0.75; 95% CI, 0.64-0.88; P <.001). This reduced risk was also present in subgroups with ≥10% weight loss (HR, 0.42; 95% CI, 0.25-0.69; P <.001), <10% weight loss (HR, 0.78; 95% CI, 0.63-0.97; P = .028), and weight gain despite GLP-1 RA use (HR, 0.71; 95% CI, 0.54-0.93; P = .014).1

Bilchick and colleagues also determined that the effect on AF reduction was most substantial with semaglutide (HR, 0.67; 95% CI, 0.53-0.84; P < .001) compared with liraglutide, dulaglutide, and tirzepatide. However, they acknowledge that this may be because more patients enrolled in the trial were on semaglutide than any other agent.1

This study adds to a growing body of evidence that GLP-1 RAs have cardioprotective effects beyond diabetes and weight management. Bilchick and colleagues note that, as future studies continue to explore this potential therapeutic pathway, investigators will need to examine their role across larger and more diverse populations.2

“We do some great interventions to help people with atrial fibrillation – in particular, we do ablations for atrial fibrillation, and this has revolutionized the field,” Bilchick said. “But even with these great ablation tools and techniques, if there is an underlying metabolic or inflammatory condition that’s promoting more arrhythmia, then being on these medications can help mitigate that and improve long-term success rates.”

Editors’ Note: Bilchick reports a disclosure with Myochron.

References

1. Bilchick KC, Palmisano T, Guarraia D. CE-534538-001 glucagon-like peptide-1 receptor agonists reduce atrial fibrillation independently of effects on weight loss and survival. Heart Rhythm. 2026;23(4). doi:10.1016/j.hrthm.2026.03.014

2. Grassley B. New Study Links GLP-1 Medications to Lower Risk of Atrial Fibrillation, Independent of Weight Loss. Heart Rhythm Society. April 23, 2026. Accessed May 11, 2026. https://www.hrsonline.org/news/glp1-medications-lower-afib-risk/