S1885 Impact of GLP-1 Receptor Agonist or GIP/GLP-1 Receptor Agonist on Clinical Outcomes in Obese Patients With Inflammatory Bowel Disease: A Propensity-Matched Analysis

Introduction: Obesity affects around 20-40% inflammatory bowel disease (IBD) patients in Western countries. Glucagon-like peptide-1 receptor agonists (GLP-1RA) alone or a combination with glucose-dependent insulinotropic polypeptide receptor co-agonists (GLP-1/GIP RA) are effective for obesity, but their impact on IBD outcomes remain unclear. We aimed to assess the clinical impact of these medications in obese IBD patients. Methods: We conducted a retrospective, propensity score-matched cohort study using TriNetX, a global federated research network. Adults with IBD and obesity (BMI ≥30) were matched 1:1 based on demographics, commodities, and baseline medication use, comparing those on GLP-1RA (Semaglutide/dulaglutide/liraglutide) or GIP/GLP-1RA (Tirzepatide) to those not on these medications. The primary composite outcome included all-cause hospitalization, steroid use, colectomy, initiation of biologic (Vedolizumab, Ustekinumab, Risankizumab), and initiation of small molecules (Upadacitinib, tofacitinib) over 10 years. Secondary outcomes included each component individually, all-cause mortality, elevated CRP ≥10 mg/L, fecal calprotectin ≥50 ug/g, acute pancreatitis, and ED visits. Subgroup analysis with just Crohn’s disease (CD) and ulcerative colitis (UC) were done. Odds ratios (ORs) with 95% confidence intervals (CIs) and P-values were reported. Results: In the matched IBD cohort (n = 5,772 per group), GLP-1RA or GIP/GLP-1RA use was associated with significantly reduced risks of primary composite outcome (51% vs 65%, OR 0.562, CI 0.522-0.606; P < 0.001), risk of hospitalization (27% vs 43.2%), all-cause mortality (2.8% vs 12.1%), steroid use (41.2% vs 49.9%), colectomy (0.4% vs 0.9%), ED visits (35.9% vs 45.4%). CRP (13.7% vs 24.1%) and fecal calprotectin (5.5% vs 7%) elevations were higher in the non-GLP-1 RA or GIP/GLP-1 RA group. However, biologic use was more in the GLP-1RA or GIP/GLP-1 RA group (2.5% vs 1.7%; OR 1.477; P = 0.003). Rates of acute pancreatitis were similar (P = 0.92). Subgroup analysis in CD and UC showed consistent findings, with reduced composite outcome risk in both. No significant difference in biologic use was seen in subgroups. Conclusion: GLP-1 RA or GIP/GLP-1 RA use in IBD patients with obesity is associated with significantly improved clinical outcomes such as hospitalization, mortality, steroid use and inflammatory burden. These findings highlight a potential therapeutic benefit in modifying disease course in obese IBD patients and warrant further prospective studies.