GLP-1 receptor agonist therapy and incident atrial fibrillation in non-diabetic adults with obesity and chronic kidney disease: a propensity matched cohort study

BACKGROUND: Obesity and chronic kidney disease (CKD) are potent risk factors for atrial fibrillation (AF), yet whether GLP-1 receptor agonists (GLP-1RAs) prevent incident AF in non-diabetic adults with obesity and CKD is unexamined. We assessed whether GLP-1RA therapy reduces 1-year AF incidence in this cardiorenal phenotype. METHODS: Using the TriNetX US Collaborative Network (66 healthcare organizations), we conducted a retrospective target trial emulation of non-diabetic adults aged 18 or older with obesity and CKD stages 3-5 diagnosed 2021-2024. Patients receiving semaglutide, liraglutide, or tirzepatide (n = 10,985) were compared with unexposed patients (n = 94,527). After propensity score matching, 7326 patients remained per cohort. The primary outcome was incident AF at 1 year; secondary outcomes included AF subtypes, ventricular tachyarrhythmias, and all-cause hospitalization. Cox models generated hazard ratios (HRs); sensitivity analyses extended follow-up to 2-3 years with landmark analyses. RESULTS: At 1 year, GLP-1RA use was associated with significantly lower incident AF (1.63% vs. 2.62%; HR 0.655, 95% CI 0.508-0.844; p = 0.001), a 34.5% relative risk reduction. Reductions were consistent for paroxysmal (HR 0.586), persistent (HR 0.482), and longstanding persistent AF (HR 0.527; all p < 0.05); permanent AF was non-significant at 1 year. Ventricular tachyarrhythmias (HR 0.556; p = 0.002) and hospitalization (HR 0.668; p < 0.001) were also significantly reduced. Benefits persisted across 2- and 3-year follow-up and remained consistent in landmark analyses. CONCLUSIONS: In non-diabetic adults with obesity and CKD, GLP-1RA therapy was associated with significant, durable reductions in incident AF, ventricular arrhythmias, and hospitalization. These findings are consistent with a possible cardiorenal benefit and support prioritizing this phenotype for dedicated randomized trials.