AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
GLP-1 Receptor Agonists, Weight Loss, and Predicted Risk of Atrial Fibrillation: An Analysis Using the CHARGE-AF Score
By Aldulimy A, Gao H, Pak J et al.
Background: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy has been shown to improve cardiovascular outcomes. However, it is uncertain whether GLP-1 RA-mediated weight loss reduces the 5-year risk of developing atrial fibrillation (AF) in high risk individuals. We hypothesize that GLP-1 RA-mediated weight loss will decrease the 5-year risk of developing AF. Methods: This retrospective chart review analysis included 652 individuals on GLP-1 RA therapy, without AF. We estimated the 5-year risk of AF using the 2013 CHARGE-AF risk prediction algorithm at baseline. We stratified individuals by risk categories into low risk (< 5.0%; N = 507) and high risk (≥ 5.0%; N = 145) groups. Participants were followed-up until the end of the analysis window or development of AF. After follow-up, we calculated weight loss and the CHARGE-AF risk score. Regression analysis was performed to determine effects of covariates. Findings were validated using a matched exposed/unexposed cohort analysis in the UK Biobank (N=1322). Results: The mean ± standard deviation age of participants was 62 ± 10 years, and 46% were non-Hispanic white (NHW). There was no significant difference in baseline weight (92.4 ± 26.2 kg vs 88.5 ± 25.5 kg; P = 0.11) or weight loss (-2.2 ± 18.6 kg vs 0.25 ± 19.6 kg; P = 20) between groups. AF risk did not change in the low risk group, but was significantly reduced in the high risk (-5.8 ± 10.5%; P < 0.001). Within the high risk group, after adjusting for age and heart failure, GLP-1 RA-mediated weight loss was a strong predictor of risk reduction among both NHW participants (R ² = 0.53; P < 0.001) and non-NHW participants (R ² = 0.88; P < 0.001). Within the validation cohort, GLP-1 RA therapy was associated with a 26.4% lower risk of incident AF (HR, 0.736; 95% CI, 0.560-0.969; P = 0.029). Conclusions: GLP-1 RA-mediated weight loss was associated with reduction in the 5-year risk of developing AF. Despite similar baseline weight and weight loss profiles, individuals at high risk had greater risk reduction compared to those with low risk. In non-NHW individuals, GLP-1 RA-mediated weight loss was the strongest predictor of risk reduction. Treatment with GLP-1 RA therapy leads to a reduction in the 5-year risk of developing AF, especially in high risk individuals.