S1468 Semaglutide and Tirzepatide Have the Most Clinical Benefit Compared to Most Weight Loss Medications in Inflammatory Bowel Disease

Introduction: Preliminary evidence indicates that anti-diabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1RA) and tirzepatide, are safe for use in patients with inflammatory bowel disease (IBD) and may have clinical benefits. A proposed mechanism behind these benefits is the reduction in systemic inflammation associated with weight loss. Thus, our study aims to evaluate the impact of weight loss medications on the progression of IBD. Methods: A retrospective cohort analysis was conducted using TriNetX, a global database of healthcare organizations. Subjects were adults over the age of 18 with either ulcerative colitis or Crohn’s disease. The study included 6 groups: those on tirzepatide, semaglutide, liraglutide, orlistat, phentermine-topiramate, and naltrexone-bupropion. The control group was not exposed to any of these weight loss medications. Patients on multiple weight loss drugs were excluded. Each group was propensity score-matched to the control based on demographics, social determinants of health, co-morbidities, and medications history. Primary outcomes studied included steroid use, hospitalization, death, and IBD-linked surgery. Results are presented as risk differences, calculated as the percent risk of the outcome in the control group minus that in the treatment group. Results: Tirzepatide and semaglutide showed significant risk reduction in all outcomes. Tirzepatide had the highest risk reduction in steroid use, hospitalization, and mortality compared to all the other agents. Liraglutide had significantly reduced risks in all categories except mortality. Orlistat had no significant benefit in any category. Phentermine-topiramate and Naltrexone-bupropion had significantly reduced risks in all variables but IBD-linked surgery. Conclusion: GLP1RA and tirzepatide had significant positive effects on the progression of IBD. In comparison, non-diabetic weight loss agents were associated with significant but modest risk reductions in some outcomes. More specifically, their impact on IBD-specific outcomes such as steroid use and IBD-related surgery was either minimal or absent. Thus, indicating these benefits may reflect overall health improvements rather than IBD-specific effects. In contrast, our findings suggest that GLP-1RA and tirzepatide may exert gut-specific anti-inflammatory effects possibly independent of weight loss, highlighting a promising avenue for future research.