Oral semaglutide reduces heavy drinking in a treatment-seeking trial

A phase 2 randomized trial of daily oral semaglutide in adults with moderate to severe alcohol use disorder (AUD) missed its primary endpoint — lab-measured craving triggered by alcohol cues — but showed significant reductions in heavy drinking days and several other drinking measures, according to results published July 29, 2026 in the American Journal of Psychiatry ^[1][2].

The double-blind trial randomized 50 treatment-seeking adults with moderate to severe AUD to oral semaglutide or placebo for eight weeks ^[2]. Those assigned to the drug took 3 mg per day for the first four weeks, then 7 mg per day for the last four weeks ^[1][2]. All participants said they wanted to reduce or stop drinking ^[1]. At the start, they reported drinking roughly six drinks per day and about five heavy drinking days per week, and nearly all fell into the World Health Organization's high or very high risk drinking categories ^[1].

What the trial found

The preregistered primary outcome was alcohol cue-elicited craving measured in a laboratory at week 6. Semaglutide did not beat placebo on that measure, nor on drinks per calendar day ^[2].

Several secondary outcomes did reach statistical significance. Semaglutide reduced 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), and day-to-day "naturalistic" craving reported outside the lab (b = −2.195; 95% CI −4.174 to −0.216) ^[2]. Alcohol-related negative consequences fell faster in the semaglutide group than in the placebo group (b = −4.618; 95% CI −8.651 to −0.585) ^[2]. By the end of treatment, 81% of the semaglutide group had dropped at least one WHO risk drinking level, compared with about 54% on placebo ^[1]; the group difference was statistically significant (Wald χ² = 4.01) ^[2].

Among the 11 participants who had used cannabis before the study, semaglutide was linked to fewer cannabis use days (b = −1.434; 95% CI −2.568 to −0.301) ^[2]. The researchers called that finding exploratory, given the very small subgroup ^[1].

The trial was small and got smaller over time: by weeks 6 through 8, analyses included 26 placebo participants and 21 semaglutide participants ^[2]. It was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Center for Advancing Translational Sciences, the Hewit Family Foundation and an anonymous family donor ^[1]. The lead author, Joseph Schacht, Ph.D., of the University of Colorado Anschutz School of Medicine, discloses advisory, consulting and research relationships with several companies, including serving as a site principal investigator for a study run by Altimmune and membership in an initiative supported by Eli Lilly and Imbrium Therapeutics ^[2].

"This study suggests oral semaglutide may help reduce heavy and harmful drinking, even in people who are not trying to quit alcohol entirely," Schacht said, adding it "could represent a new treatment option for alcohol use disorder, particularly for those who have not benefited from existing medications" ^[1].

Why it matters for patients

Semaglutide is approved in the U.S. for type 2 diabetes and, in other formulations, for weight loss — not for alcohol use disorder ^[1]. This trial does not change that. It is an 8-week, 50-person phase 2 study whose main prespecified endpoint was negative, which means the positive secondary results are best read as signals that need confirmation, not proof of benefit ^[2].

The pattern is worth understanding, though. The drug did not lower craving measured in a lab setting, but it did lower self-reported craving in everyday life and changed how much people drank on the days they drank ^[2]. The authors frame this as reducing harmful drinking rather than producing abstinence ^[1].

Safety and side-effect data from this trial are not described in the sources provided, so how tolerable these doses were in people with AUD is not yet known here. The sources also do not identify the specific oral semaglutide product used, or report any outcomes past eight weeks.

What happens next

The researchers concluded that larger clinical trials are warranted and that continued development of semaglutide for AUD is justified ^[1][2]. No timeline, sponsor or trial design for a larger study is named in these sources, and no regulatory filing for an alcohol-related indication has been announced in them.