Association between GLP-1 receptor agonists and alcohol-related hospitalisations among adults with alcohol use disorder: multi-target trial emulation study.

OBJECTIVE: To evaluate the association between use of newer glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide, tirzepatide) and alcohol-related hospitalisations among adults with alcohol use disorder (AUD) and type 2 diabetes (T2D) or obesity.Retrospective cohort study using target trial emulation. SETTING: Electronic health record data from a collective of US healthcare systems. PARTICIPANTS: Adults with AUD and T2D or obesity who started a newer GLP-1 RA (semaglutide or tirzepatide) or a relevant active comparator between 1 January 2018 and 31 December 2024. INTERVENTIONS: Initiation of a newer GLP-1 RA compared with an active comparator across four target trials: (1) anti-diabetic medication (ADM) trial, (2) anti-obesity medication (AOM) trial, (3) medications for alcohol use disorder with T2D (MAUD-T2D) trial, and (4) medications for alcohol use disorder with obesity (MAUD-obesity) trial. MAIN OUTCOME MEASURES: Time to first alcohol-related emergency department visits or hospitalisation within 1 year of treatment initiation. Non-alcohol-related hospitalisation was assessed as a negative control outcome. Propensity score based methods (weighting and matching) were used to control confounding and Cox proportional hazards models were used to estimate treatment effects. RESULTS: A total of 40 703 adults met study criteria, including 18 676 in the ADM trial, 9391 in the AOM trial, 8942 in the MAUD-T2D trial and 11 198 in the MAUD-obesity trial. Initiation of a newer GLP-1 RA was associated with a lower hazard of alcohol-related hospitalisation in the ADM trial (HR 0.74, 95% CI 0.62 to 0.89 vs sulfonylureas; HR 0.78, 95% CI 0.65 to 0.92 vs other ADMs), the AOM trial (HR 0.68, 95% CI 0.54 to 0.85 vs other AOMs), the MAUD-T2D trial (HR 0.37, 95% CI 0.29 to 0.46) and the MAUD-obesity trial (HR 0.35, 95% CI 0.26 to 0.47). CONCLUSIONS: Among adults with AUD and T2D or obesity, initiation of newer GLP-1 RAs was associated with a lower observed risk of alcohol-related hospitalisation.