Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial

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).

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.

Semaglutide did not significantly reduce laboratory-assessed craving or drinks per day compared with placebo, but significantly reduced heavy drinking days (b=-0.580, 95% CI=-1.012, -0.148). Semaglutide also significantly reduced drinks per drinking day (b=-1.177, 95% CI=-2.307, -0.047), naturalistic alcohol craving (b=-2.195, 95% CI=-4.174, -0.216), and cannabis use days (b=-1.434, 95% CI=-2.568, -0.301). Semaglutide reduced alcohol-related consequences at a significantly greater rate than placebo (b=-4.618, 95% CI=-8.651, -0.585). Significantly more participants in the semaglutide group than the placebo group reduced their risk drinking level by one or more levels (Wald χ²=4.01).

These findings confirm previous results among non-treatment seekers with less severe AUD and suggest that continued development of semaglutide for AUD is warranted.