Adjunctive GLP-1 RA treatment of limited benefit in stable IBD patients with obesity, diabetes

In patients with stable inflammatory bowel disease (IBD) receiving advanced therapies who have comorbid obesity and/or diabetes, adjunctive treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide or tirzepatide does not appear to improve clinical outcomes, according to new research.

Researchers used observational data from an administrative claims database to emulate a target trial of GLP-1 RAs in stable patients with IBD (no steroid use, no IBD-related hospitalization or surgery, and stable dose of IBD therapy for >6 months) with comorbid obesity and/or diabetes.  

Two separate cohorts were established: those with background 5-aminosalicylic acid (5-ASA) or no IBD-directed medications (cohort 1) and those with background advanced therapies and/or immunomodulators (cohort 2). These cohorts comprised GLP-1 RA users and nonusers, matched according to propensity scores.

Outcomes included 1-year risk of relapse (composite of IBD-related hospitalization, surgery, or prednisone use) and safety.

Cohort 1 included 2,028 GLP-1 RA users (mean age 63 years, 63 percent female, 71 percent had ulcerative colitis) and 2,028 nonusers. In this cohort, the risk of relapse was similar between GLP-1 RA users and nonusers (7.9 percent vs 7.9 percent, respectively; risk ratio [RR], 1.01, 95 percent confidence interval [CI], 0.82–1.24). Safety outcomes were also comparable between the two groups (7 percent vs 7.9 percent, respectively; RR, 0.88, 95 percent CI, 0.71–1.10), with 36 percent of GLP-1 RA users discontinuing the medication within 1 year.

Cohort 2 included 346 GLP-1 RA users (mean age 59 years, 62 percent female, 43 percent had ulcerative colitis) and 346 nonusers. There were no significant between-group differences observed in the risk of relapse (12.4 percent vs 15.6 percent, respectively; RR, 0.80, 95 percent CI, 0.55–1.15) and safety outcomes (5.5 percent vs 6.6 percent, respectively; RR, 0.88, 95 percent CI, 0.48–1.58). A third of GLP-1 RA users (33 percent) discontinued the medication within 1 year.