Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial

OBJECTIVE: Accumulating preclinical and observational evidence suggests that glucagon-like peptide-1 receptor agonists, including semaglutide, reduce alcohol consumption. This phase 2 double-blind, randomized, parallel-arm trial evaluated the effects of oral semaglutide on alcohol craving and consumption among treatment-seeking adults with alcohol use disorder (AUD). METHODS: Fifty individuals with moderate to severe AUD were randomized to receive semaglutide (3 mg/day for 4 weeks, then 7 mg/day for 4 weeks) or placebo for 8 weeks. The primary outcome was laboratory-based alcohol cue-elicited craving at week 6. Key preregistered secondary outcomes were heavy drinking days and drinks per day during the last 4 weeks of treatment. Effects on other alcohol consumption measures, naturalistic alcohol craving, alcohol-related negative consequences, World Health Organization risk drinking level, and cannabis use were also explored. RESULTS: =4.01). CONCLUSIONS: These findings confirm previous results among non-treatment seekers with less severe AUD and suggest that continued development of semaglutide for AUD is warranted.