AIMS: To examine emerging clinical evidence, real-world data, and neurobiological mechanisms supporting the repurposing of semaglutide as a novel treatment for alcohol use disorder (AUD) METHODS: Of records identified, articles were selected based on clinical relevance to AUD outcomes and mechanisms of action. Included studies ranged from hypothesis-generating designs to confirmatory randomized controlled trials in non-treatment-seeking individuals and patients diagnosed with AUD, with several cohorts enriched for comorbid obesity.

RESULTS: Randomized controlled trials demonstrated that once-weekly semaglutide significantly reduced alcohol cravings and drinks per drinking day, even in non-treatment-seeking populations. Large-scale cohort studies showed a reduction in AUD-related hospitalizations for patients on semaglutide compared to non-users. Dual agonists like tirzepatide also showed significant reductions in binge drinking odds and AUDIT scores, with reductions in alcohol craving and consumption appearing most pronounced among individuals with comorbid obesity or metabolic disease. Mechanistically, preclinical and early human data indicate GLP-1 receptor activity in the VTA and nucleus accumbens modulates mesolimbic reward circuitry to attenuate dopamine-mediated reinforcement, alongside indirect behavioral and satiety effects.

CONCLUSIONS: GLP-1 receptor agonists show early promise in reducing alcohol craving and consumption, particularly in individuals with comorbid metabolic disease. No GLP-1 receptor agonist currently carries FDA approval for alcohol use disorder, and all discussed clinical applications still remain investigational. Definitive randomized trials in AUD-only populations are still needed. Current evidence remains limited by small sample sizes, brief follow-up periods, self-reported outcomes, and potential confounding from weight loss.