1778-P: Opioids and Risk of Gastrointestinal Outcomes among Patients Receiving GLP-1RAs

Introduction and Objective: Gastrointestinal (GI) adverse events are frequent with GLP-1RA therapy, and opioids may further impair GI motility. We compared the risk of motility-related GI outcomes across commonly prescribed opioids in individuals receiving GLP-1RAs. Methods: Using three US administrative claims databases (2016-2025), we identified adults with T2D who initiated oxycodone, hydrocodone, or tramadol while receiving GLP-1RAs. Motility-related GI events, including severe constipation, gastroparesis, and bowel obstruction, were evaluated. Incidence rates per 100 person-years and hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards models weighted by propensity score matching weights. Results: Among 411,188 patients (mean age 62.8 years, 53.8% female), 24.4% initiated oxycodone, 48.5% hydrocodone, and 27.1% tramadol. Compared with tramadol (weighted IR 6.1/100 PY), oxycodone (weighted IR 10.2/100 PY) was associated with increased risk of motility-related GI events (HR 1.63, 95% CI 1.41-1.88), while hydrocodone (weighted IR 7.3/100 PY) showed a modestly increased risk (HR 1.15, 95% CI 1.00-1.32). Oxycodone also demonstrated higher risk compared with hydrocodone (HR 1.42, 95% CI 1.25-1.61). Conclusion: Among GLP-1RA users, GI risk varied by opioid, highest with oxycodone and lowest with tramadol. These findings highlight clinically relevant differences in GI risk profiles among commonly used opioids in patients receiving GLP-1RAs. Disclosure S. Bea: None. E. Patorno: Research Support; Current; Boehringer Ingelheim International GmbH, AstraZeneca, Bayer AG, National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute. Other - Royalties; Current; UpToDate. S. Kattinakere Sreedhara: None. D. Wexler: Other - Data Monitoring Committee; Ended; Novo Nordisk. Other - Data Monitoring Committee; Current; Amgen Inc. S. Cromer: Other - Spouse is employee of Depuy Synthes; Current; Johnson & Johnson. J. Paik: None. K. Bykov: None. Funding American Diabetes Association (1-25-PDF-66), National Institute of Health (K01AG068365)