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

Abstract

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/m2). 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.