Semaglutide, Tirzepatide and Clinically Recorded Alcohol‐Related Outcomes in Type 2 Diabetes: A Target Trial Emulation

ABSTRACT Aims To compare the risk of incident alcohol use disorder (AUD) among adults with Type 2 diabetes (T2D) initiating semaglutide, tirzepatide or sodium‐glucose cotransporter‐2 inhibitors (SGLT2i). Materials and Methods We conducted a target trial emulation using de‐identified electronic health record data from the TriNetX research network (June 2022–January 2025). Adults with T2D newly initiating semaglutide, tirzepatide or an SGLT2i were included. The primary outcome was clinically recorded hospitalization or emergency department (ED) visits for AUD. Cox proportional hazards models with 1:1 propensity score matching (PSM) estimated hazard ratios (HRs) and 95% CIs. Sensitivity and subgroup analyses as well as secondary outcomes assessed the robustness of the findings. Results During a mean follow‐up of 0.81–1.02 years, the incidence rates (IRs) of clinically recorded hospitalization or ED visits for AUD were 2.42 versus 4.53 per 1000 person‐years for semaglutide versus SGLT2i, with an HR of 0.54 (95% CI, 0.45–0.64). Similarly, the IRs were 2.34 versus 3.98 per 1000 person‐years for tirzepatide versus SGLT2i, with an HR of 0.61 (95% CI, 0.46–0.83). In the direct comparison of semaglutide versus tirzepatide, IRs were 2.43 and 2.36 per 1000 person‐years, respectively, with no difference in risk (HR, 0.98; 95% CI, 0.73–1.31). Results were consistent across sensitivity and subgroup analyses and secondary outcomes. Conclusions In adults with T2D, semaglutide and tirzepatide were associated with lower rates of clinically recorded AUD‐related outcomes than SGLT2i, with no difference between the two GLP‐1RA medications.