Atrial fibrillation (AF) risk appeared lower among patients with advanced chronic kidney disease (CKD) receiving glucagon-like peptide-1 agonists (GLP-1a), extending emerging cardiometabolic observations into a high-risk CKD population. Presented at the ACC.26 Conference, the retrospective TriNetX analysis evaluated whether GLP-1a therapy influenced AF outcomes in patients with stage 3-5 CKD. 

Previous analyses suggested lower AF rates with GLP-1a therapy in patients with type 2 diabetes mellitus (T2DM) and obesity, but evidence in severe CKD, particularly among non-dialysis patients, has remained limited.

The analysis identified 3,628,998 adults with stage 3-5 CKD between January 2016 and September 2025. Patients receiving dialysis or kidney transplantation were excluded. New GLP-1a users were propensity score-matched 1:1 with non-users for age, sex, ethnicity, body mass index, diabetes, hypertension, ischemic heart disease, heart failure, and thyroid disorders. The matched cohort included 99,462 GLP-1a users and 99,462 non-users, with a mean age of 69 years. Men accounted for 45.3% of the cohort, 20.2% were African American, and 81.2% had diabetes mellitus.

Over a median follow-up of 1.5 years, AF-related outcomes occurred less frequently among GLP-1a users. A total of 7460 events occurred in the GLP-1a group compared with 9198 events among non-users. GLP-1a use was associated with an 18% lower risk of incident AF (adjusted HR 0.82; 95% CI 0.80-0.85) and a 43% lower risk of AF-related events (adjusted HR 0.57; 95% CI 0.47-0.68).

The findings suggest that GLP-1a therapy may be associated with lower AF burden in patients with advanced CKD, although the observational design does not establish causality, and residual confounding cannot be excluded.