EVALUATING POUCH RELATED OUTCOMES WITH GLUCAGON LIKE PEPTIDE-1 RECEPTOR ANTAGONISTS IN PATIENTS WITH ILEAL POUCH ANAL ANASTOMOSIS—A DATABASE STUDY IN THE UNITED STATES

Abstract INTRODUCTION Prevalence of obesity in patients with ileal pouch anal anastomosis (IPAA) is rising with recent data suggesting prevalence of 20%. Studies have shown that obesity is associated with negative outcomes in patients with IPAA. Glucagon-like peptide-1 receptor agonists (GLP1RA) are approved anti-obesity medications for which there are data to suggest favorable outcomes in patients with inflammatory bowel disease (IBD), though their impact on patients with IPAA is unknown. METHODS We conducted a retrospective cohort study using de-identified patient data from the TriNetX database, including adult patients diagnosed with ulcerative colitis (UC) who underwent IPAA between January 1, 2005, and January 1, 2025. Patients were excluded if lacking documentation of UC, IPAA surgery, or medication exposure. Two cohorts were defined: patients with an IPAA and GLP1RA exposure, and those without GLP1RA use. GLP1RA exposure required active use during each follow-up interval. Propensity score matching (1:1) was adjusted for demographics and confounders. Logistic regression and a univariate Cox proportional hazards models were used to assess IPAA outcomes, including pouchitis, antibiotic use, steroid therapy, Crohn’s-like disease of the pouch (CLDP), hospitalization, pouch failure, and use of advanced therapies, at 1, 3, and 5 years following GLP1RA exposure (Table 2 legend). RESULTS Before PSM, there were 37, 92, and 140 patients with an IPAA and GLP1RA use over 1, 3, and 5 years; and 5,552, 5,497, and 5,449 with an IPAA without GLP1RA use over 1, 3, and 5 years, respectively. After PSM, 37, 92, and 140 patients were included in each cohort at 1, 3, and 5 years. GLP1RA users were older at IPAA (39.5±16.1 vs 38.6±16.9) and more often obese (Table 1). Incidence of Pouchitis and advanced therapy use were similar between groups (Table 2). GLP1RA use was associated with lower antibiotic use at 3 years (37.0% vs 52.2%, OR 0.54; p = 0.038) and 5 years (37.9% vs 59.3%, OR 0.42; p < 0.001), and reduced steroid use at 3 years (28.3% vs 54.3%, OR 0.33; p < 0.001) and 5 years (28.6% vs 52.9%, OR 0.36; p < 0.001). Hospitalizations were also fewer at 1 year (40.5% vs 64.9%, OR 0.37; p = 0.036), 3 years (42.4% vs 71.7%, OR 0.29; p < 0.001), and 5 years (40.0% vs 67.9%, OR 0.32; p < 0.001). No GLP1RA users experienced pouch failure, and Crohn’s-like disease of the pouch was numerically lower but not statistically significant (Table 2). CONCLUSIONS While GLP1RA use was not associated with differences in the incidence of pouchitis, it was consistently associated with lower rates of antibiotic use, steroid use, and hospitalization at longer-term follow-up. Further studies are needed to better define the impact that GLP1RA exposure has on patients with IPAA, including more granular outcomes such as clinical disease activity scores and pouchoscopy.