The effects of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on alcohol-related outcomes: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on alcohol-related outcomes in adults with or without alcohol use disorder (AUD). METHODS: A systematic review and meta-analysis following PRISMA guidelines searched PubMed, Embase, and Cochrane Library up to May 3, 2025. Eligible studies included randomized controlled trials (RCTs) and observational studies assessing GLP-1RAs (e.g., Semaglutide, Liraglutide, Exenatide, and Dulaglutide) versus placebo, no treatment, or other interventions in adults. Outcomes were alcohol consumption (defined as total intake or drinks per drinking day, measured as standardised mean difference [SMD]), alcohol craving (SMD), and alcohol-related events (hazard ratio [HR]). Random-effects models with Restricted Maximum Likelihood estimation and Hartung-Knapp adjustment were used. Separate AUD and SUD meta-analyses addressed outcome heterogeneity, with intoxication reported narratively. RESULTS: Three RCTs (N = 430) and six observational studies (N = 2,740,207) were included. RCTs showed non-significant reductions in alcohol consumption (SMD: -0.24, 95% CI: -0.70, 0.23), drinks per drinking day (SMD: -0.23, 95% CI: -0.64, 0.19), and craving (SMD: -0.14, 95% CI: -2.84, 2.55), with Semaglutide showing greater craving reduction (p = 0.024). Observational studies showed reduced alcohol-related events (HR: 0.64, 95% CI: 0.59-0.69, p < 0.001), with separate analyses confirming effects for AUD (HR: 0.66, 95% CI: 0.63-0.70) and SUD (HR: 0.66, 95% CI: 0.18-2.48), and intoxication (HR: 0.50). Semaglutide and GIP/GLP-1RAs had more potent effects (p < 0.001). CONCLUSION: Observational studies suggest a decrease in alcohol-related events, but RCTs have effects on alcohol consumption and craving that remain non-significant. Larger RCTs are needed. PROSPERO ID: CRD420251045294.