A common diabetes and weight-loss medication called semaglutide has shown remarkable effectiveness in reducing alcohol consumption in people with alcohol use disorder and obesity, according to the first major clinical trial of its kind. Researchers found that participants receiving semaglutide reduced their heavy drinking days by 41% over 26 weeks, compared to just 26% in the placebo group, with total alcohol consumption dropping by over 70% in the treatment group.

Why Is This Finding Important for Addiction Treatment?

Current medications approved by the FDA for alcohol use disorder are rarely used. Only about 2% of adults with alcohol use disorder take one of the three available medications: disulfiram, acamprosate, or naltrexone. These drugs work by reducing cravings or causing severe nausea when alcohol is consumed, but they face significant barriers to adoption among both patients and physicians. The new findings suggest semaglutide could offer a different approach that might appeal to a much broader population, especially those who are also struggling with obesity.

The trial, conducted at Mental Health Centre Copenhagen and led by researchers including Nora Volkow, M.D., director of the National Institute on Drug Abuse (NIDA), involved 108 treatment-seeking participants evenly divided between men and women, with an average age of about 50. All participants had a body mass index (BMI) of 30 or higher, which is the threshold for obesity, and were diagnosed with alcohol use disorder. Participants had experienced an average of 17 heavy drinking days in the month before the trial began.

The study was randomized, double-blinded, and placebo-controlled, meaning neither the participants nor the researchers knew who received the actual medication versus placebo. One group of 54 people received weekly injections of semaglutide at 2.4 milligrams per dose for 26 weeks, while the other group received placebo injections. All participants also had access to up to 10 sessions of cognitive behavioral therapy (CBT) focusing on motivation, craving strategies, and relapse prevention.

How Does Semaglutide Work in the Brain?

Semaglutide belongs to a class of drugs called GLP-1 receptor agonists, which work by stimulating receptors for a peptide called GLP-1 (glucagon-like peptide-1). This peptide is naturally produced in the small intestine and also in the brain, where it plays a role in appetite regulation and reward pathways. Researchers have become interested in using GLP-1 agonists for addiction because these brain receptors are located in areas involved in reward and addiction. Animal studies have already shown that GLP-1 receptor agonists can significantly reduce alcohol consumption in models of alcohol addiction.

The theory behind why semaglutide might work for both obesity and alcohol use disorder is compelling. Researchers believe the drug targets overlapping neurobiological mechanisms that regulate both metabolism and reward-related pathways shared between these two conditions. In this trial, weight loss was closely related to reductions in alcohol consumption in the semaglutide group, supporting this hypothesis.

What Were the Specific Results?

The results were substantial across multiple measures. Participants receiving semaglutide experienced the following improvements:

• Heavy drinking days: Reduced by 41% on average, compared to 26% in the placebo group
• Total alcohol consumption: Dropped by over 70%, from an average of 78 ounces of pure alcohol over 30 days (equivalent to 130 shots of 80-proof spirits) down to 23 ounces (about 39 shots)
• Drinks per drinking day: Declined by 3.5 drinks, compared to 2.1 drinks in the placebo group
• Weight loss: Participants lost an average of 25 pounds, compared to 5 pounds in the placebo group
• WHO drinking risk levels: Declined by two levels after 26 weeks, reflecting a shift toward safer drinking patterns

The greatest benefits were seen in two specific subgroups: people who reported 12 to 17 heavy drinking days per month at baseline, and those diagnosed with severe alcohol use disorder. The placebo group also showed improvement, declining by 46% in total alcohol consumption, which researchers attributed to the placebo effect, participants' motivation to reduce drinking, and the cognitive behavioral therapy all participants received.

Biomarkers and metabolic measures also showed much greater improvement in the semaglutide group compared to placebo. The researchers noted that these reductions in drinking were "associated with long-term reductions in alcohol-related negative consequences, improvement in mental health, and aligns with improvement in self-evaluated general and psychological health" in the semaglutide group, though they acknowledged these improvements were modest.

What About Side Effects?

The most common adverse effects reported were gastrointestinal in nature and occurred more frequently in the semaglutide group, but most were short-lived and none were severe. This safety profile is consistent with what researchers have observed in other trials of semaglutide for weight loss and diabetes.

"Findings from this trial provide support for broadening the indication for semaglutide to include alcohol use disorder in patients with a BMI of 30 or greater, which could benefit millions," the research team concluded.

Research team led by Anders Fink-Jensen, M.D., Mental Health Centre Copenhagen

The potential impact is significant. Approximately 890 million adults globally have a BMI over 30, and in the United States alone, an estimated 8 million adults have obesity combined with high alcohol consumption.

What Comes Next for This Research?

While the results are promising, researchers emphasized that future studies will need to replicate and expand these findings. Key areas for additional investigation include:

• Larger and more diverse cohorts: The current trial included 108 participants who were nearly all White, so researchers need to test semaglutide in larger groups representing different racial and ethnic backgrounds
• Lower dosages: The trial used 2.4 milligrams per week, but researchers want to determine if lower doses might be effective and potentially reduce side effects
• Long-term follow-up: This trial lasted 26 weeks, but researchers need to understand whether benefits persist beyond this timeframe and whether participants maintain their progress after treatment ends

The findings were published in The Lancet, a peer-reviewed medical journal, and represent the first major clinical trial testing semaglutide specifically in treatment-seeking patients with alcohol use disorder who were also obese. The research team included George F. Koob, Ph.D., a 1999 Brain and Behavior Research Foundation Distinguished Investigator, alongside leading addiction experts from the National Institute on Drug Abuse.

This research opens a new avenue for treating a condition that affects millions of people worldwide. By targeting the shared neurobiological pathways underlying both obesity and alcohol use disorder, semaglutide may offer a treatment option that addresses both conditions simultaneously, potentially making it more appealing to patients and clinicians than existing alternatives.