S1603 GLP-1 Agonists in Inflammatory Bowel Disease: Does the Choice Between Semaglutide and Dulaglutide Matter?

Introduction: The prevalence of obesity is rising worldwide with a parallel rise in inflammatory bowel disease (IBD). Studies on impact of obesity on IBD are conflicting, some suggest increased adverse events in IBD population with obesity and improved outcomes in IBD patients with obesity undergoing treatment with glucagon-like peptide (GLP-1) agonists. However, there has been no comparison of individual GLP-1 agonists on outcomes of IBD. We compared 3-, 5-, and 10-year outcomes of patients with IBD with co-existing obesity on semaglutide vs Dulaglutide. Methods: We performed a retrospective cohort study using the TrinNetX database, a comprehensive multi-institutional dataset. The study included patients aged ≥18 years and BMI ≥30 kg/m2 with a diagnosis of IBD (Crohn’s disease and Ulcerative colitis) from 1/1/2014 to 4/30/2025. Patients were categorized based on whether they received only semaglutide or only Dulaglutide any time after the diagnosis of IBD. The primary aim was to assess outcomes of IBD at 3, 5, and 10 years. One to one propensity score matching was applied for age, gender, race, tobacco use, alcohol use, comorbidities, BMI, IBD medications (mesalamine, steroids, biologics), and fecal calprotectin. Results: After propensity matching, a total of 2581 patients were included in each group. Semaglutide was associated with a lower 3-, 5-, and 10-year risk of intestinal obstruction and use of biologics than dulaglutide. Additionally, semaglutide was associated with a lower risk of mortality than dulaglutide over 3 and 5 years. On the other hand, risk of colectomy, fistula formation, deep venous thrombosis, pulmonary embolism, Clostridium difficile infection, and use of systemic steroids over 3-, 5-, and 10- years was similar between the 2 groups. Semaglutide was also associated with lower mean levels of erythrocyte sedimentation rate over 3-, 5-, and 10- years, while there was no significant difference in mean levels of fecal calprotectin and serum C-reactive protein over this time period. Conclusion: This study provides evidence that semaglutide may offer superior long-term outcomes in IBD patients with obesity compared to dulaglutide, particularly in reducing intestinal obstruction, biologic use, and mortality over 3 and 5 years. The findings highlight semaglutide’s potential as a dual-purpose agent for managing both metabolic disease and IBD-related inflammation. Further prospective studies are warranted to validate these findings and explore the underlying mechanisms.