Background Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have shown promise for alcohol use disorder (AUD).

Objective To evaluate the association between use of newer GLP-1 RAs (semaglutide, tirzepatide) and alcohol-related hospitalizations among adults with AUD and either type 2 diabetes (T2D) or obesity.

Methods This retrospective target trial emulation study used electronic health record data from Truveta to identify adults with AUD and either T2D or obesity, who initiated a newer GLP-1 RA (semaglutide, tirzepatide) or relevant active comparator between 2018 and 2024. Four target trials were constructed to reflect clinically distinct populations and comparators: (1) ADM trial (patients with T2D and comparators of other anti-diabetic medications [ADM]), (2) AOM trial (patients with obesity but not T2D and comparators of other anti-obesity medications [AOM]), (3) MAUD-T2D trial (patients with T2D and markers of more severe AUD and comparators of medications for alcohol use disorder [MAUD]), (4) MAUD-obesity trial (patients with obesity, no T2D, and markers of more severe AUD and comparators of MAUD). The primary endpoint was time to alcohol-related hospitalization. Non-alcohol-related hospitalization served as a negative control outcome. Propensity score-based methods (weighting and matching) were used to control for confounding. Cox proportional hazards models were used to estimate the treatment effect of newer GLP-1 RA in four target trials.

Results A total of 40,260 patients were identified, including 18,515 in the ADM trial, 9,256 in the AOM trial, 9,975 in the MAUD and T2D trial, and 11,039 in the MAUD and obesity trial. GLP-1 RAs were associated with a lower hazard of alcohol-related hospitalization in the ADM (HR [95% CI]: 0.70 [0.59 - 0.83] vs. sulfonylureas; 0.73 [0.62 - 0.86] vs. other ADMs), AOM (HR: 0.59 [0.48 - 0.74]), MAUD-T2D (HR: 0.36 [0.29 - 0.46]), and MAUD-obesity (HR: 0.32 [0.23 - 0.43]) trials. No significant differences were observed for non-alcohol-related hospitalizations for ADM and MAUD-T2D trials.

Conclusion Newer GLP-1 RAs were associated with reduced risk of alcohol-related hospitalization across clinically distinct populations.

The authors have declared no competing interest.

This study was funded by Truveta Inc.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Normalized electronic health record data are de-identified by expert determination under the HIPAA Privacy Rule before being made available to researchers. In accordance with 45 C.F.R. Para. 46.101 Protection of Human Subjects, our study did not require Institutional Review Board approval because it used only deidentified medical records. All data used in this study are publicly available to Truveta subscribers and may be accessed at studio.truveta.com.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data used in this study are available to all Truveta subscribers and may be accessed at studio.truveta.com.