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

ImportanceObesity 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. ObjectiveTo 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. DesignThis 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. ParticipantsAID Adults ([≥]18 years) who were eligible for AOM treatment. ExposureGLP-1RA use versus non-use. Main Outcomes and MeasuresThe 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. ResultsThe 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/m{superscript 2}). 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 RelevanceAmong 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. Key PointsO_ST_ABSQuestionC_ST_ABSIs the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) associated with cardiovascular and thromboembolic outcomes among adults with obesity and autoimmune disease (AID)? FindingsIn this target trial emulation using 2014-2024 electronic health record data from the OneFlorida+ network, 13,204 GLP-1RA users were compared with 13,204 matched non-users. GLP-1RA use was associated with significantly lower risks of pulmonary embolism, venous thromboembolism, emergency department visits, and all-cause mortality, with marginal associations for stroke or transient ischemic attack. MeaningAmong adults with obesity and AID, GLP-1RA therapy may confer thromboembolic and survival benefits without increasing cardiovascular risk.