{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:51:02Z","timestamp":1792183862237,"version":"4.4.0"},"reference-count":19,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Patients with type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) face elevated risk of hepatobiliary complications. The biliary safety of GLP-1 and dual GLP-1\/GIP receptor agonists in this population is uncertain. Methods: We conducted a retrospective cohort study using the TrinetX LIVE global health research network. Adults (\u226518 years) with coexisting T2DM and IBD were assigned to exposure (semaglutide or tirzepatide) or comparator (no GLP-1\/GIP therapy) cohorts. The index was first prescription (or matched date). Primary outcomes\u2014cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis\u2014were identified by ICD-10 codes. Propensity score matching (1:1 greedy nearest neighbor; caliper 0.1 SD) balanced demographics, comorbidities, GI surgeries, and antidiabetic medications. Results: After propensity score matching, 32,052 patients were included (16,026 per cohort), achieving excellent covariate balance with standardized mean differences &lt; 0.1 for nearly all variables. GLP-1\/GIP agonist use was associated with significantly lower risks of multiple biliary complications. Cholelithiasis occurred in 3.5% of GLP-1\/GIP users compared with 6.3% of nonusers (risk ratio [RR] 1.81, 95% CI 1.64\u20132.00; hazard ratio [HR] 1.27, 95% CI 1.14\u20131.41; p &lt; 0.001). Cholecystitis similarly occurred less frequently among users (0.8% vs. 2.2%; RR 2.74, 95% CI 2.24\u20133.34; HR 1.85, 95% CI 1.50\u20132.27; p &lt; 0.001). Choledocholithiasis was also reduced in the GLP-1\/GIP cohort (0.6% vs. 1.5%; RR 2.72, 95% CI 2.14\u20133.46; HR 1.90, 95% CI 1.48\u20132.44; p &lt; 0.001). Cholangitis events were rare in both groups (0.1% vs. 0.2%) with no significant difference on survival analysis (HR 1.07, 95% CI 0.58\u20131.97; p = 0.08). Conclusions: In adults with T2DM and IBD, GLP-1 and dual GLP-1\/GIP receptor agonists are associated with substantially reduced risks of gallstone-related complications. These real-world data support the gastrointestinal safety of GLP-1\u2013based therapy in a high-risk population and suggest possible biliary protective effects warranting prospective, agent-specific studies.<\/jats:p>","DOI":"10.3390\/jcm14248882","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:57:24Z","timestamp":1765879044000},"page":"8882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Guts, Glucose, and Gallbladders: The Protective Role of GLP-1\/GIP Receptor Agonists Against Biliary Complications in Patients with Type 2 Diabetes and Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Muhammad Ali Ibrahim","family":"Kazi","sequence":"first","affiliation":[{"name":"Luminis Health Anne Arundel Medical Center, Annapolis, MD 21401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanmeet","family":"Singh","sequence":"additional","affiliation":[{"name":"Luminis Health Anne Arundel Medical Center, Annapolis, MD 21401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nowreen","family":"Haq","sequence":"additional","affiliation":[{"name":"Luminis Health Anne Arundel Medical Center, Annapolis, MD 21401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2020","journal-title":"J. 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