Glucagon‐Like Peptide‐1 Receptor Agonists and Cardiovascular Events in Adults With Obesity and Autoimmune Disease: A Target Trial Emulation

Background Obesity and autoimmune diseases (AIDs) are each associated with elevated risk of cardiovascular and thromboembolic events. 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. This study evaluated the association between GLP‐1RA use and major adverse cardiovascular and thromboembolic event risk among adults with obesity and AID. Methods This retrospective cohort study emulated a target trial using 2014 to 2024 electronic health record data from the OneFlorida+ network. Adults (aged ≥18 years) with AID and obesity eligible for antiobesity medication therapy were included. Exposure was defined as GLP‐1RA use versus nonuse. Participants were matched using 1:1 time‐dependent propensity scores. The primary outcomes were myocardial infarction, stroke or transient ischemic attack, pulmonary embolism, venous thromboembolism, and coronary revascularization. Secondary outcomes included hospitalization, emergency department visits, and all‐cause mortality. Results We matched 13 204 GLP‐1RA users and 13 204 nonusers (mean ± SD age, 54.7 ± 14.5 years; 73.4% women; mean body mass index, 37 kg/m 2 ). GLP‐1RA use was associated with lower hazard of stroke/transient ischemic attack (hazard ratio [HR], 0.87 [95% CI, 0.76–0.99]; P =0.039), pulmonary embolism (HR, 0.69 [95% CI, 0.56–0.86]; P =0.001), venous thromboembolism (HR, 0.83 [95% CI, 0.72–0.95]; P =0.007), emergency department visits (HR, 0.79 [95% CI, 0.75–0.83]; P <0.001), and mortality (HR, 0.56 [95% CI, 0.47–0.66]; P <0.001). Conclusions Among adults with obesity and AID, GLP‐1RA use was associated with reduced thromboembolic events, lower emergency department use, and decreased mortality, suggesting potential cardiovascular and survival benefits in this high‐risk population.