1714-P: Semaglutide, Tirzepatide, and Risk of Alcohol Use Disorder in Type 2 Diabetes: A Target Trial Emulation

Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce the risk of developing alcohol use disorder (AUD), yet real-world evidence on the effects of semaglutide and tirzepatide, the most potent GLP-1RAs, is limited. This study aimed to compare the risk of incident AUD among adults with type 2 diabetes (T2D) who were treated with semaglutide, tirzepatide or sodium-glucose cotransporter-2 inhibitors (SGLT2i). Methods: We conducted three target trial emulations using deidentified, individual-level electronic health records from the TriNetX network (June 2022-January 2025). Adults with T2D newly initiating semaglutide, tirzepatide, or an SGLT2i were included. The primary outcome was hospitalization or emergency department (ED) encounters for AUD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models after 1:1 propensity score matching (PSM). Sensitivity analyses (including negative control outcome calibration), secondary outcomes (incident AUD and alcohol-associated liver disease), and subgroup analyses were performed to assess the robustness of the findings. Results: After PSM, 162,014 patients initiated semaglutide vs SGLT2i, and 69,166 patients initiated tirzepatide vs SGLT2i. Both semaglutide (HR, 0.54; 95% CI, 0.45-0.64) and tirzepatide (HR, 0.61; 95% CI, 0.46-0.83) were associated with significantly lower risks of hospitalization or ED visits for AUD than SGLT2i use. In a direct comparison of 89,624 patients initiated semaglutide vs tirzepatide, the risk was similar (HR, 0.98; 95% CI, 0.73-1.31). Findings were consistent across secondary outcomes, NCO calibration, and multiple subgroup analyses. Conclusion: In adults with T2D, both semaglutide and tirzepatide were associated with reduced risks of AUD compared with SGLT2i, with comparable effects between the two GLP-1RA medications. These findings support the potential repurposing of GLP-1RAs for AUD prevention and treatment. Disclosure H. Tang: None. B. Zhang: None. Y. Lu: None. Y. Chen: None.