Abstract Background Diabetes mellitus (DM) is associated with worse outcomes in patients with inflammatory bowel disease (IBD). GLP-1 receptor agonists may confer anti-inflammatory benefits, but their effect on IBD outcomes in diabetic patients receiving infliximab remains unclear. This study examined whether GLP-1 exposure influences disease activity, complications, and hospitalization risk in this population. Methods A retrospective cohort study was conducted using the TriNetX U.S. Collaborative Network. Adults (≥18 years) with IBD and diabetes who initiated infliximab between 2015–2024 were identified and stratified into GLP-1–exposed (Cohort 1) and GLP-1–naïve (Cohort 2) groups. Pregnancy-positive patients were excluded. Propensity score matching (1:1) produced 625 patients per cohort. Outcomes assessed over 730 days included bloody stools, infection, abdominal pain, inpatient admission, nausea/vomiting, malnutrition, vitamin D deficiency, DVT/PE, and acute pancreatitis. Acute pancreatitis was prespecified as an outcome; however, TriNetX could not return analyzable data due to insufficient patient events. Risk ratios, odds ratios (OR), and hazard ratios (HR) with 95% CIs were reported. Results GLP-1–exposed patients experienced significantly lower risks across multiple adverse outcomes. Compared with GLP-1–naïve patients, GLP-1 use was associated with reduced risk of bloody stools (15.7% vs 24.8%; OR 0.564, 95% CI 0.425–0.747; p 0.001), infections (25.0% vs 36.2%; OR 0.587, 95% CI 0.460–0.749; p 0.001), abdominal pain (39.7% vs 47.7%; OR 0.722, 95% CI 0.577–0.903; p = 0.004), and inpatient admissions (32.2% vs 42.6%; OR 0.640, 95% CI 0.508–0.806; p 0.001). Additional reductions were observed in malnutrition (6.1% vs 16.0%; OR 0.340, 95% CI 0.230–0.503; p 0.001), vitamin D deficiency (6.2% vs 9.9%; OR 0.604, 95% CI 0.398–0.917; p = 0.017), and DVT/PE (5.1% vs 8.3%; OR 0.595, 95% CI 0.377–0.937; p = 0.024). Kaplan-Meier analyses demonstrated improved survival free of most adverse outcomes. Acute pancreatitis could not be evaluated due to insufficient case counts returned by the network. Conclusion Among diabetic patients with IBD treated with infliximab, GLP-1 receptor agonist exposure was associated with substantially reduced risks of gastrointestinal bleeding, infection, abdominal pain, hospitalization, malnutrition, vitamin D deficiency, and thromboembolic events. Although acute pancreatitis was included as a prespecified outcome, no analyzable data were returned. These findings suggest a potential protective role for GLP-1 therapy in this high-risk population and highlight the need for further investigation. Conflict of interest: Dr. Johal, Jashanveer: No conflict of interest Patel, Om: No conflict of interest Hussein, Abdallah: No conflict of interest Al-Bataineh, Mahmoud: No conflict of interest Schneider, Yecheskel: No conflict of interest Hyman, Jason: No conflict of interest
Johal et al. (Thu,) studied this question.