Glucagon-like peptide-1 receptor agonists associated with improved clinical outcomes in patients with inflammatory bowel disease: a retrospective cohort study

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated anti-inflammatory effects in preclinical models of inflammatory bowel disease (IBD), yet clinical data remain limited. This study aimed to assess the association between GLP-1 RAs exposure and disease-related outcomes, treatment patterns, and healthcare utilization in patients with IBD. We conducted a retrospective, propensity score–matched cohort study using data from the TriNetX Analytics Research Network. Adults diagnosed with Crohn’s disease or ulcerative colitis between 2006 and 2022 were matched 1:1 based on GLP-1 RAs exposure. Patients with confounding comorbidities were excluded. Key outcomes included 5-year mortality, IBD-related surgeries and complications, medication use, and healthcare utilization. A total of 11,016 matched IBD patients were included (GLP-1 RAs: n = 5508; no GLP-1 RAs: n = 5508). Exposure to GLP-1 RAs was associated with a significantly lower 5-year mortality rate (8.05% vs 10.03%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.54–0.78, p < 0.0001). Rates of IBD-related surgeries (HR 0.53, 95% CI 0.39–0.72) and complications (HR 0.81, 95% CI 0.70–0.93) were also reduced. Moreover, patients in the GLP-1 RAs group experienced fewer overall healthcare encounters (χ² = 136.52, p < 0.0001). Significant differences were observed in corticosteroid (p < 0.0001) and advanced biologic use (p < 0.0001), although rank biserial correlation was small (0.04 and − 0.11, respectively), and findings on medication use did not persist in subgroup analyses of ulcerative colitis and Crohn’s disease patients. Our findings suggest a potential disease-modifying effect of GLP-1 RAs beyond glycemic control, especially in reducing mortality, complications, surgeries, and healthcare use. However, the clinical relevance of reduced medication use warrants further investigation through prospective trials.