Small Trial Finds Oral Semaglutide Reduced Heavy Drinking Days in Alcohol Use Disorder

A small randomized trial testing oral semaglutide as a treatment for alcohol use disorder missed its primary goal of reducing cue-triggered craving in a laboratory setting, but found significant reductions on several secondary measures of drinking, according to results published online July 29, 2026 in The American Journal of Psychiatry.

The Phase 2 trial, registered as NCT05892432 and led by researchers at the University of Colorado School of Medicine, enrolled 50 treatment-seeking adults with moderate to severe alcohol use disorder. Participants were randomly assigned to oral semaglutide, marketed as Rybelsus, titrated from 3 mg per day for 4 weeks to 7 mg per day for the following 4 weeks, or to a matched placebo, in a double-blind design. The study was sponsored by the University of Colorado, Denver with funding from the National Institute on Alcohol Abuse and Alcoholism, according to the trial's ClinicalTrials.gov record.

The primary outcome was laboratory-based alcohol cue-elicited craving measured at week 6. According to the published abstract, semaglutide did not significantly reduce this craving measure or drinks per day compared with placebo. Key preregistered secondary outcomes were heavy drinking days and drinks per day during the final 4 weeks of treatment.

Several other measures did show significant differences favoring semaglutide. The trial reported significant reductions in heavy drinking days (b=-0.580, 95% CI -1.012 to -0.148), drinks per drinking day (b=-1.177, 95% CI -2.307 to -0.047), naturalistic alcohol craving reported outside the lab (b=-2.195, 95% CI -4.174 to -0.216), cannabis use days (b=-1.434, 95% CI -2.568 to -0.301), and alcohol-related negative consequences (b=-4.618, 95% CI -8.651 to -0.585). A significantly greater proportion of participants on semaglutide reduced their World Health Organization risk drinking level by one or more categories compared with placebo, based on a Wald chi-square test.

In a press release from the University of Colorado Anschutz Medical Campus, lead investigator Joseph Schacht, an associate professor in the Department of Psychiatry, said the study suggests oral semaglutide may help reduce heavy and harmful drinking, even in people who are not trying to quit alcohol entirely. The university's release noted that most side effects were mild and that adherence and completion rates were high, and said the team is planning larger follow-up trials.

The authors wrote that the findings confirm earlier results seen among non-treatment-seeking people with less severe alcohol use disorder, and that they support continued development of semaglutide for this indication, rather than establishing it as an effective treatment on their own.

The trial's small size, single-population design, and mixed primary-versus-secondary results are limitations the study authors themselves point to in supporting further research rather than treatment claims. Semaglutide remains approved only for type 2 diabetes and, at higher doses, for chronic weight management; it has no approved indication for alcohol use disorder, and this report does not constitute medical or dosing guidance.