ADJUNCTIVE GLP-1 RECEPTOR AGONISTS IN CROHN’S DISEASE: REDUCED STEROID DEPENDENCE AND HOSPITALIZATIONS IN A REAL-WORLD MULTI-NETWORK COHORT

Abstract BACKGROUND Obesity affects nearly half of patients with Crohn’s disease in the United States and contributes to complex disease management. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for obesity and diabetes, their impact on Crohn’s disease outcomes remains largely unexplored. Preclinical studies suggest anti-inflammatory and gut barrier–protective effects, yet clinical data on hard outcomes such as steroid dependence, hospitalization, and surgery are lacking. Defining the role of GLP-1 RAs in Crohn’s disease is critical as obesity prevalence rises and integrated care models across gastroenterology, endocrinology, and obesity medicine become more essential. METHODS We performed a retrospective, real-world cohort study using the TriNetX research network. Adults with Crohn’s disease and overweight/obesity were eligible if they initiated a GLP-1 RA or had no exposure; index dates were aligned within the same calendar quarter. Propensity score matching (1:1) balanced demographics, comorbidities, prior IBD therapies, healthcare utilization, and baseline steroid exposure. Outcomes were assessed over 12 months, with steroid dependence as the primary endpoint. Secondary outcomes included all-cause hospitalization, Crohn’s-related surgery, and persistence on advanced IBD therapy. Analyses employed risk differences, risk ratios, and Cox proportional hazards models in an intention-to-treat framework, with multiple sensitivity analyses performed. RESULTS After matching, 546 GLP-1 RA users and 546 non-users were well balanced across demographic and clinical factors. GLP-1 RA therapy was associated with significantly lower steroid dependence (52.9% vs 62.8%; risk difference –9.9%, p = 0.0009) and fewer hospitalizations (2.3% vs 3.7%, p = 0.02). Kaplan–Meier analysis demonstrated reduced hospitalization risk and improved persistence on advanced therapy in GLP-1 RA users (HR 0.74, 95% CI 0.64–0.87, p = 0.0002). Rates of major abdominal surgery were comparable between groups, with no signal of increased surgical risk. Findings remained robust in subgroup and sensitivity analyses, including restriction to patients on advanced IBD therapies at index. CONCLUSION In this large, multi-network real-world analysis, adjunctive GLP-1 RA use in overweight and obese Crohn’s disease patients was associated with reduced steroid dependence, fewer hospitalizations, and improved persistence on advanced therapy, without increasing surgical risk. These results provide the first large-scale evidence supporting GLP-1 RAs as a safe and potentially beneficial adjunct in Crohn’s disease management. As GLP-1 RA prescribing rapidly expands, prospective studies and guideline development are urgently needed to define their role in integrated IBD and metabolic care.