GLP-1 Receptor Agonists and Cardiovascular Events in Adults with Obesity and Autoimmune Disease: A Target Trial Emulation.

Importance: Obesity and autoimmune diseases (AID) are each associated with elevated risk of cardiovascular and thromboembolic events due to chronic systemic inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular and metabolic benefits in patients with type 2 diabetes and obesity, but their effects in patients with obesity and comorbid AID remain uncertain. Objective: To evaluate the association between GLP-1RA use and the risk of major adverse cardiovascular and thromboembolic events among adults with obesity and AID eligible for anti-obesity medication (AOM) therapy. Design: This retrospective cohort study emulated a target trial using 2014-2024 electronic health record data from the OneFlorida+ network, which includes 21 million individuals across Florida, Georgia, and Alabama. Adults with obesity and AID who met AOM eligibility criteria were included. Propensity score matching (1:1) was applied using a time-dependent framework to balance baseline covariates between GLP-1RA users and non-users. Participants: AID Adults (≥18 years) who were eligible for AOM treatment. Exposure: GLP-1RA use versus non-use. Main Outcomes and Measures: The primary outcomes were myocardial infarction, stroke or transient ischemic attack (TIA), pulmonary embolism (PE), venous thromboembolism (VTE), and coronary revascularization. Secondary outcomes included hospitalization, emergency department (ED) visits, and all-cause mortality. Results: The matched cohort included 13,204 GLP-1RA users and 13,204 non-users (mean age, 54.7 ± 14.5 years; 73.4% female; mean BMI, 37 kg/m2). Compared with non-users, GLP-1RA users had lower incidence rates (per 1000 person-years) of PE (6.4 vs 9.5), VTE (16.6 vs 20.4), and mortality (9.5 vs 16.9). GLP-1RA use was associated with lower hazard of stroke/TIA (HR, 0.87 [95% CI, 0.76-0.99]; P = .039), PE (HR, 0.69 [95% CI, 0.56-0.86]; P = .001), VTE (HR, 0.83 [95% CI, 0.72-0.95]; P = .007), ED visits (HR, 0.79 [95% CI, 0.75-0.83]; P = .000), and mortality (HR, 0.56 [95% CI, 0.47-0.66]; P = .000). Conclusions and Relevance: Among adults with obesity and AID, GLP-1RA use was associated with reduced thromboembolic events, lower emergency department utilization, and decreased mortality. These findings suggest potential cardiovascular and survival benefits of GLP-1RAs in a high-risk, understudied population.