Comparative outcomes for tirzepatide versus glucagon-like peptide-1 receptor agonists in patients with inflammatory bowel disease: a national propensity matched study

Background/Aims: Evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may improve disease-specific outcomes for inflammatory bowel disease (IBD). Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist, may offer additional benefits. We compared clinical and safety outcomes among patients with IBD treated with tirzepatide versus GLP-1RAs. Methods: Patients aged ≥ 18 years with IBD were identified within a retrospective multiinstitutional U.S. database who were prescribed tirzepatide or GLP-1RA between May 2022 and January 2025. Propensity score matching (1:1) was performed for demographics, comorbidities, and IBD medications. Outcomes were assessed over 18 months and included intravenous (IV) steroid use, intestinal surgery, emergency department visits, hospitalization, and a composite of IV steroids and surgery. Adverse outcomes were assessed. Results: After matching, 3,042 patients (mean age, 54.6 years; 71.3% female) were analyzed in each cohort. Median follow-up was 540 days (interquartile range, 478-540 days) for tirzepatide versus 540 days (interquartile range, 540-540 days) for GLP-1RA. Patients taking tirzepatide had a significantly reduced risk of IV steroid use (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.68-0.94) and composite IBD outcomes (aHR, 0.86; 95% CI, 0.73-0.97) with similar risk of hospitalization, emergency department visit and receipt of intestinal surgery. In patients with ulcerative colitis specifically, tirzepatide was similarly associated with a reduced risk of IV steroid use (aHR, 0.82; 95% CI, 0.69-0.97). Adverse outcome risks were similar. Conclusions: Patients with IBD prescribed tirzepatide may have lower risk of IV steroid use compared to those taking GLP-1RAs. Prospective studies are warranted to validate these results and explore underlying mechanisms.