Abstract 4371433: Cardiovascular Outcomes Associated with GLP-1 Receptor Agonists in Obese Adults Without Diabetes: A Propensity-Matched Real-World Study

Background: Obesity is a well-established risk factor for atrial fibrillation (AF) and adverse cardiovascular outcomes. Glucagon-Like Peptide 1 receptor agonists (GLP-1 RAs), initially developed for glycemic control, have shown promise in reducing cardiovascular risk independent of diabetes. However, their effect on arrhythmic and cardiovascular outcomes in non-diabetic obese populations remains poorly defined. Research Question: In obese adults without diabetes, does GLP-1 RA therapy reduce the 1-year incidence of atrial fibrillation, mortality, heart failure, and major adverse cardiovascular events (MACE) compared to standard care? Methods: We utilized the TriNetX US Collaborative Network to identify adults ≥18 years with obesity and no history of diabetes from 2014–2022. Patients initiating GLP-1 RAs formed the treatment cohort. Controls were patients with obesity and no GLP-1 RA exposure. One-to-one propensity score matching (n=118,781 per group) was performed on demographics, cardiovascular comorbidities, and medication use. Outcomes were assessed at 1 year, excluding patients with pre-existing conditions. The primary outcome was incident AF while secondary outcomes were all-cause mortality, heart failure (HF), and three-point major adverse cardiovascular events (3P-MACE: acute MI, stroke, cardiac arrest). Results: GLP-1 RA use was associated with significant reductions across all endpoints: Atrial Fibrillation: 0.4% vs 0.7% (RR 0.605 [95% CI 0.542–0.675]; HR 0.563 [95% CI 0.504–0.628]; p<0.001); Mortality: 0.2% vs 1.0%, (RR 0.203 [95% CI 0.177–0.232]; HR 0.190 [95% CI 0.165–0.218]; p<0.001); Heart Failure: 0.6% vs 1.2% (RR 0.479 [95% CI 0.438–0.525]; HR 0.446 [95% CI 0.407–0.489]; p<0.001); 3P-MACE: 0.4% vs 0.9% (RR 0.429 [95% CI 0.384–0.480]; HR 0.399 [95% CI 0.357–0.446]; p<0.001). Kaplan-Meier survival curves confirmed significantly higher event-free survival in the GLP-1 RA cohort for all endpoints. No increase in AF subtypes (paroxysmal, persistent, chronic) was observed. Propensity-matching yielded well-balanced cohorts across age, sex, race, comorbidities, and medication exposure. Conclusion: Among obese adults without diabetes, GLP-1 RA was associated with a substantial reduction in new-onset AF, all-cause mortality, HF, and MACE at one year. These findings support a potential role for GLP-1 RAs in primary cardiovascular prevention in obesity, beyond their metabolic benefits, and underscore the need for dedicated randomized controlled trials.