Effects of glucagon-like peptide-1 receptor agonists on alcohol consumption: a systematic review and meta-analysis.

BACKGROUND: Alcohol use disorder (AUD) is a major global health burden with high relapse rates and limited treatment uptake. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for type 2 diabetes and obesity, may also reduce alcohol consumption by modulating central reward pathways. METHODS: We performed a systematic review and meta-analysis following PRISMA guidelines (PROSPERO CRD420251009075). Randomized controlled trials (RCTs) and observational studies were included if they assessed the effect of GLP-1 RAs on alcohol-related outcomes in adults with hazardous drinking or AUD. The search covered all databases from inception to June 1, 2025. The primary outcome was change in Alcohol Use Disorders Identification Test (AUDIT) scores (range 0-40), a validated screening tool assessing hazardous use, dependence, and alcohol-related harm. Alcohol use was defined as self-reported consumption (drinks or units per week, grams per day), with thresholds for risky drinking determined by study-specific definitions (e.g., ≥14 drinks/week for men, ≥7 for women). Secondary outcomes included relapses, abstinence, alcohol-related diagnoses, intoxication or hospitalization, biomarkers (e.g., phosphatidylethanol [PEth], γ-GT), and neuroimaging measures of craving, reward, and cue-reactivity. FINDINGS: Fourteen studies (four RCTs, ten observational; n = 5,262,268) were included. GLP-1 RAs studied were Semaglutide, liraglutide, dulaglutide, exenatide, and tripeptide. Pooled analysis demonstrated a significant reduction in AUDIT scores (mean difference -7.81 points; 95% CI -9.02 to -6.60; I= 87.5%). RCTs also reported reduced drinking days, units per drinking day, and cravings particularly with Semaglutide. GLP-1 RA use was associated with reduced alcohol intake, relapse rates, and incidence of alcohol-related diagnoses, especially in individuals with type 2 diabetes or obesity prescribed Semaglutide or liraglutide. Population-based studies showed lower risks of incident and recurrent AUD, intoxication, and hospitalization. Biomarker analyses (PEth, γ-GT) demonstrated reductions with GLP-1 RA use, and neuroimaging studies reported attenuated alcohol cue reactivity and dopaminergic signaling. Weight loss and metabolic improvements reinforced abstinence and treatment adherence. INTERPRETATION: GLP-1 RAs, particularly Semaglutide and liraglutide, reduce alcohol use as measured by AUDIT scores and show beneficial effects on consumption, relapse, and alcohol-related morbidity. Mechanistic evidence supports modulation of craving and reward pathways. These findings suggest that GLP-1 RAs are promising candidates for repurposing in AUD management, especially for patients with comorbid diabetes or obesity. Large, dedicated RCTs are needed to confirm efficacy and define optimal therapeutic strategies. FUNDING: No funding was received for this study.