Adjunctive GLP1 Receptor Agonists in Patients with Inflammatory Bowel Diseases and Obesity and/or Diabetes: A Target Trial Emulation.

BACKGROUND & AIMS: We conducted a target trial emulation study to examine the effect of 2 glucagon-like peptide-1 receptor agonists (semaglutide and tirzepatide) on clinical outcomes in patients with inflammatory bowel diseases with obesity and/or diabetes. METHODS: We emulated a target trial of glucagon-like peptide-1 receptor agonists in eligible, stable patients with inflammatory bowel diseases (no steroid use, no inflammatory bowel disease-related hospitalization or surgery and stable dose of inflammatory bowel disease therapy for >6 months) with comorbid obesity and/or diabetes using observational data from an administrative claims database (OptumLabs Data Warehouse) between 2018 and 2023. We created 2 separate cohorts: (cohort 1) background 5-aminosalicylates or no inflammatory bowel disease-directed medications; and (cohort 2) background advanced therapies and/or immunomodulators. We compared the 1-year risk of relapse (composite of inflammatory bowel disease-related hospitalization, surgery, or prednisone use) and safety with glucagon-like peptide-1 receptor agonist initiation vs noninitiation, after 1:1 propensity score matching. RESULTS: Cohort 1: In 2028 patients initiated on glucagon-like peptide-1 receptor agonists (age, 63 ± 11 years; 63% female; 71% with ulcerative colitis) matched 1:1 to glucagon-like peptide-1 receptor agonist noninitiators, there was no difference in risk of relapse (7.9% vs 7.9%; relative risk, 1.01; 95% confidence interval, 0.82-1.24) or safety outcomes (7.0% vs 7.9%; relative risk, 0.88; 95% confidence interval, 0.71-1.10); 36% patients discontinued glucagon-like peptide-1 receptor agonists within 1 year. Cohort 2: In 346 patients initiated on glucagon-like peptide-1 receptor agonists (age, 59 ± 12 years; 62% female; 43% with ulcerative colitis) matched 1:1 to glucagon-like peptide-1 receptor agonist noninitiators, no significant difference was observed in the risk of relapse (12.4% vs 15.6%; relative risk, 0.80; 95% confidence interval, 0.55-1.15) or safety outcomes (5.5% vs 6.6%; relative risk, 0.88; 95% confidence interval, 0.48-1.58); 33% of patients discontinued glucagon-like peptide-1 receptor agonists within 1 year. CONCLUSIONS: Adjunctive treatment with semaglutide or tirzepatide does not improve outcomes in patients with stable inflammatory bowel diseases on advanced therapies and/or immunomodulators and/or 5-aminosalicylates.