Repurposing GLP-1 receptor agonists for alcohol use disorder: a systematic review and meta-analysis

Abstract

Background: Alcohol use disorder (AUD) affects nearly half a billion people globally and is associated with significant physical and psychiatric comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for diabetes and obesity, have shown promise in modulating reward-related brain pathways, suggesting potential benefits in the management of AUD. Methods: This systematic review and meta-analysis, registered in PROSPERO and conducted per PRISMA guidelines, assessed the effects of GLP-1RA use on AUD and alcohol-related outcomes in adults with obesity or type 2 diabetes mellitus. Five databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) were searched up to September 30, 2025. Random-effects models were applied, and sensitivity analyses examined result stability. No subgroup or meta-regression analyses were performed owing to the small number of eligible studies. Results: Five observational cohort studies (three on AUD diagnosis, two on alcohol-related hospitalization) were included, with sample sizes ranging from 4,321 to > 53,000 participants. GLP-1RA use was associated with a 28% lower risk of AUD diagnosis (HR = 0.72, 95% CI 0.59–0.89; I² = 65%). For alcohol-related hospitalization, a non-significant reduction was observed (HR = 0.76, 95% CI 0.57–1.01; I² = 77%). Leave-one-out sensitivity analyses confirmed the direction and magnitude of the AUD finding but highlighted the limited evidence base for hospitalization. Conclusion: GLP-1RA use was associated with a reduced risk of AUD diagnosis, with a possible but non-significant reduction in alcohol-related hospitalization. Effects may be mediated through modulation of mesolimbic reward pathways and the gut–brain axis. Further large-scale trials are warranted to confirm these findings.