Semaglutide might reduce how much people with alcohol use disorder drink when they do drink

An experimental study of individuals with moderate to severe alcohol use disorder found that semaglutide did not reduce a primary laboratory measure of alcohol craving or drinks per day compared to placebo. However, it significantly reduced the number of heavy drinking days, the number of drinks consumed on drinking days, naturalistic cravings, and alcohol-related negative consequences. The World Health Organization risk drinking level was reduced as well. The paper was published in the American Journal of Psychiatry.

Semaglutide is a medication that mimics the action of a naturally occurring hormone called glucagon-like peptide-1, or GLP-1. It was originally developed to help control blood glucose in people with type 2 diabetes.

Semaglutide stimulates insulin release when blood glucose is elevated, reduces glucagon secretion, and slows the rate at which food leaves the stomach. It acts on brain systems involved in appetite, helping people feel full sooner and reducing hunger and food intake. Because of these effects, semaglutide is now also used for long-term weight management in people who meet specific medical criteria.

Depending on the formulation and indication, it may be given as a once-weekly injection or taken as a daily tablet. Treatment usually begins with a low dose that is gradually increased. The goal of this is to reduce gastrointestinal side effects such as nausea, vomiting, diarrhea, and constipation. Semaglutide is generally used alongside dietary, physical-activity, and other lifestyle measures rather than as a replacement for them.

Study author Joseph P. Schacht and his colleagues conducted a study in which they evaluated the safety and initial efficacy of oral semaglutide for treating individuals with moderate to severe alcohol use disorder. Alcohol use disorder is a medical condition characterized by a persistent pattern of alcohol use that becomes difficult to control and causes significant problems in a person’s health, relationships, work, or daily functioning.

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Study authors hypothesized that semaglutide would reduce cue-elicited alcohol cravings and alcohol consumption. Cue-elicited alcohol cravings are cravings for alcohol elicited by things that a person associates with alcohol drinking (e.g. seeing or holding an alcoholic beverage, tasting alcohol, being in a place where they usually consume alcohol).

Study participants were 50 individuals with moderate or severe alcohol use disorder who were seeking treatment. All were 21 years old or older and had a body mass index (BMI) of 25 or higher, meaning they were overweight or obese. Men were consuming 28 drinks per week or more, while it was 21 drinks or more for women.

Study participants were randomly assigned to either receive semaglutide for 8 weeks (3 mg/day for 4 weeks, then 7 mg/day for 4 weeks) or a placebo for the same period. The placebo was a capsule that looked just like the semaglutide capsule and was packaged in identical blister packs. Participants did not know whether they were taking semaglutide or the placebo, and this was unknown to the study personnel working with them as well.

Study authors tracked participants’ medication adherence and assessed their reactivity to alcohol cues. Participants rated their alcohol cravings on a single-item rating scale and by completing a multi-item questionnaire called the Alcohol Craving Questionnaire – Short Form. Before screening for participation, between screening and being assigned to a group, and throughout the treatment, participants reported their alcohol and cannabis use. Study authors derived the numbers of drinks per calendar day and heavy drinking days per week from this data.

At the start of the study and at the end of treatment, participants completed magnetic resonance imaging of their brains while completing an alcohol cue reactivity task, allowing study authors to measure how much their brain reacts to alcohol cues. The results of these brain scans were not part of this report and will be published in a future paper. Study authors also collected or derived a number of other measures of participants’ drinking behavior or behavior related to alcohol.

Results showed that the two groups did not differ significantly in how they rated their alcohol cravings on the single-item scale after week 6 of treatment. The overall number of drinks per day was also not significantly different between the two groups.

However, in the last 4 weeks, semaglutide significantly reduced the number of heavy drinking days. Participants receiving semaglutide also had significantly lower scores on the multi-item alcohol craving questionnaire at week 6, as well as lower naturalistic cravings in their daily lives. In the last 4 weeks, participants who received semaglutide had fewer drinks per drinking day, but not fewer drinking days. Furthermore, semaglutide significantly reduced alcohol-related negative consequences and reduced the number of days participants used cannabis, among those who were cannabis users at the start of the study.

“In summary, among treatment-seeking individuals with AUD [alcohol use disorder], oral semaglutide significantly reduced alcohol consumption, naturalistic alcohol craving, alcohol-related problems, and cannabis use. Effects on alcohol consumption were of greater magnitude than extant AUD pharmacotherapies,” study authors concluded.

The study contributes to the scientific understanding of the effects of semaglutide on treating alcohol use disorder. However, it should be noted that the treatment only lasted 8 weeks, whereas semaglutide is typically used over much longer periods and often continuously for other medical indications. Further studies should therefore examine whether the observed effects persist, increase, or change during longer-term treatment.

The paper, “Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial,” was authored by Joseph P. Schacht, Joseph T. Sakai, Kristen Raymond, and Robert Shelton.