Cardiovascular outcomes associated With GLP-1 and dual GLP-1/GIP receptor agonists in patients with type 2 diabetes and inflammatory bowel disease: A retrospective real-world cohort study

Introduction Individuals with co-morbid T2D and IBD represent a uniquely high-risk group, facing amplified cardiovascular risk through synergistic inflammatory and metabolic pathways, in whom conventional cardiometabolic strategies (such as dietary and lifestyle changes, weight loss, blood pressure and lipid optimization, metformin therapy, SGLT2 inhibitor therapy) may be insufficient due to the overlap between metabolic disease and chronic inflammatory disease processes. At present, the literature available on the role of incretin-based therapy in the treatment of T2D in patients with co-morbid IBD is limited. We aimed to evaluate the association of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists with cardiovascular outcomes in individuals with T2DM and IBD. This study is not intended as a direct comparison of the efficacy of GLP-1 agonists and dual GLP-1/GIP receptor agonists in patients with T2D and IBD. Both drug classes were analyzed as a combined incretin-based therapy exposure group to reflect real-world prescribing patterns and maximize statistical power. Methods We conducted a retrospective cohort study using the TriNetX global federated research network, identifying adults (≥18 years) with T2D and IBD between 2015–2024. Patients prescribed GLP-1 or dual GLP-1/GIP were compared with non-users following 1:1 propensity score matching on demographics, comorbidities, and medication use. Relative risks (RR) and Hazard Ratios (HR) with 95% confidence intervals (CI) were calculated, with significance defined as p < 0.05. Results After matching 16,118 patients per cohort from among a total matched population of 32,236 patients, GLP-1 or GLP-1/GIP receptor agonist therapy was associated with lower hazard ratios across all outcomes, including myocardial infarction (HR 0.701, 95% CI 0.637–0.771), chronic ischemic heart disease (HR 0.936, 95% CI 0.896–0.978), heart failure (HR 0.777, 95% CI 0.737–0.820), atrial fibrillation/flutter (HR 0.838, 95% CI 0.788–0.890), sudden cardiac death (HR 0.694, 95% CI 0.605–0.795), ischemic stroke (HR 0.781, 95% CI 0.707–0.862), deep vein thrombosis (HR 0.642, 95% CI 0.586–0.702), and pulmonary embolism (HR 0.722, 95% CI 0.640–0.815). Conclusions In patients with comorbid T2D and IBD, GLP-1 and GLP-1/GIP receptor agonists were associated with significant reductions in ischemic, arrhythmic, and thromboembolic cardiovascular outcomes. These findings highlight the potential role of incretin-based therapies in improving cardiovascular risk management in this high-risk population. However, the present study does not establish the comparative efficacy of the two classes of drugs in this patient population, and the findings may be associational rather than causal. Both drug classes were analyzed as a combined exposure group. Mechanistic explanations proposed in this paper should be considered hypothesis-generating rather than confirmed by the current observational study design.