GLP-1 Analog Use is Associated With Improved Disease Course in Inflammatory Bowel Disease: A Report from the Epi-IIRN

Background and Aims: The growing use of glucagon-like peptide 1 (GLP-1) analogs for type 2 diabetes mellitus (DM2) and obesity necessitates studies about their use in patients with inflammatory bowel diseases (IBD). Methods: Data on patients with DM2 were retrieved from an Israeli nationwide cohort of patients with IBD (epi-IIRN), recording GLP-1 analog exposure for at least 6 months. The primary outcome was poor disease outcomes (ie, composite of steroid dependence, initiation of advanced IBD therapy, hospitalization, surgery, or death). Cox proportional hazard models with time-varying covariables were used to assess the impact of GLP-1 use on outcomes during follow-up. Results: We included 3737 patients (24 338 patient-years) with IBD and DM2 [50.4% ulcerative colitis (UC)], of whom 633 were treated with GLP-1 analogs. Accounting for demographics IBD/DM2 related variables, medication use, and laboratory measurements, GLP-1 analog use was associated with reduced composite outcome in the full cohort (adjusted hazard ratio [aHR] 0.74, 95% confidence interval [CI] 0.62-0.89) and in each subtype [UC (aHR 0.71, 95% CI 0.52-0.96) and Crohn s disease (aHR 0.78, 95% CI 0.62-0.99)]. Similar trends were seen in multivariate analyses of each individual outcome, although only hospitalization was significant (aHR 0.74, 95% CI 0.61-0.91). The protective effect of GLP-1 analogs was seen in patients with obesity (aHR 0.61, 95% CI 0.50-0.77), but not in non-obese (aHR 0.94, 95% CI 0.67-1.31). Conclusions: GLP-1 analogs are associated with improved outcomes in IBD, specifically in patients with obesity. The mechanisms of these effects require further investigation as well as their role in patients without DM2.