New Study Reports Fewer Heavy Drinking Days With Semaglutide
How does a hormone involved in metabolism interact with the brain’s reward system? Researchers in Denmark explored this question in a clinical trial involving adults with both obesity and alcohol use disorder. Over 26 weeks, participants receiving semaglutide experienced greater reductions in several alcohol-related measures than those receiving placebo. The findings add to ongoing research examining possible connections between metabolic signaling, dopamine-related reward pathways, and alcohol-related behaviors.
Note: This article is intended for general information and educational purposes. It summarizes scientific research in accessible language for a broad audience and is not an official scientific press release.
A randomized clinical trial published in May 2026 in The Lancet investigated whether semaglutide, a GLP-1 peptide that acts as a GLP-1 receptor agonist and is approved for obesity treatment, was associated with changes in alcohol consumption among adults living with both obesity and alcohol use disorder. The study enrolled individuals actively seeking treatment and compared once-weekly semaglutide injections with placebo over a 26-week period.
The research was conducted by Mette Kruse Klausen, Signe Keller Justesen, Julie Niemann Pedersen, Line Rasmussen, Andreas Jensen, Mathias Ebbesen Jensen, Ulla B. Knorr, Marianne Lerbæk Bergmann, Jens Juul Holst, Bolette Hartmann, George F. Koob, Helene Benveniste, Nora D. Volkow, Claus Thorn Ekstrøm, Gitte Moos Knudsen, Tina Vilsbøll, and Anders Fink-Jensen. The authors are affiliated with the Mental Health Centre Copenhagen, Copenhagen University Hospital–Bispebjerg and Frederiksberg, Rigshospitalet, the University of Copenhagen, the University Hospital of Southern Denmark, the Novo Nordisk Foundation Center for Basic Metabolic Research, the Steno Diabetes Center Copenhagen, Yale University, the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
The investigators aimed to determine whether semaglutide could reduce heavy drinking days compared with placebo while also evaluating changes in overall alcohol consumption, alcohol craving, body weight, laboratory biomarkers, and safety outcomes over the course of the study.
What the Researchers Investigated
Alcohol use disorder is a chronic condition characterized by impaired control over alcohol consumption and repeated episodes of heavy drinking. Although behavioral therapies and several medications are available, treatment options remain limited. According to the authors, this has encouraged continued research into new therapeutic approaches.
Semaglutide belongs to a class of medications known as GLP-1 receptor agonists. Originally developed for diabetes and obesity, these drugs also influence appetite regulation as well as reward-related brain pathways. Earlier animal studies, observational research, and smaller human trials had suggested that GLP-1 receptor agonists might also influence alcohol-related behaviors, providing the rationale for this study.
The investigators therefore aimed to determine whether once-weekly semaglutide could reduce heavy drinking among adults with both obesity and alcohol use disorder who were actively seeking treatment.
How the Study Was Conducted
The trial was conducted at the Mental Health Centre Copenhagen in Denmark and lasted 26 weeks. A total of 108 adults between 18 and 70 years of age participated, including 53 women and 55 men. Every participant had obesity (BMI of at least 30 kg/m²) together with moderate-to-severe alcohol use disorder and was seeking professional treatment.
Participants were randomly assigned to receive either semaglutide or placebo, with 54 people in each group. Neither the participants nor the investigators performing assessments knew which treatment had been assigned. To maintain blinding during injections, participants wore blindfolds and listened to music through headphones so they could not hear the distinctive clicking sound of the semaglutide injection pen.
Semaglutide treatment began with a weekly dose of 0.25 mg, which was gradually increased every four weeks until participants reached either the target dose of 2.4 mg or the highest dose they could tolerate. Participants assigned to the placebo group followed an identical injection schedule using saline injections.
Importantly, medication was not the only intervention. Every participant was also offered up to ten standardized 45-minute cognitive behavioral therapy sessions focused on motivation, craving management, relapse prevention, and strategies for reducing alcohol use. No nutritional counseling or weight-loss program was provided as part of the study.
The primary outcome was the change in the percentage of heavy drinking days after 26 weeks. Researchers also evaluated total alcohol consumption, alcohol craving, body weight, laboratory biomarkers associated with alcohol use, metabolic measures, and safety outcomes.
What Makes This Study New
According to the authors, this is the first randomized, double-blind, placebo-controlled trial to evaluate the full 2.4 mg dose of semaglutide in treatment-seeking adults with both obesity and alcohol use disorder.
Previous evidence had largely come from preclinical studies, registry analyses, or smaller clinical investigations. One earlier randomized trial evaluated another GLP-1 receptor agonist, exenatide, but did not observe an overall reduction in heavy drinking days across the entire study population. Another recent randomized trial examined a lower dose of semaglutide in non-treatment-seeking adults with alcohol use disorder and reported reduced alcohol intake during a laboratory self-administration task. According to the authors, the present trial builds on previous research by evaluating treatment-seeking participants receiving the full obesity dose of semaglutide.
Key Findings From the Study
Overall, 81% of participants completed the entire 26-week intervention. Compared with placebo, participants receiving semaglutide showed greater improvements across several alcohol-related outcomes.
1. Alcohol-Related Outcomes
- Fewer heavy drinking days. Participants receiving semaglutide experienced a 41.1-percentage-point reduction in heavy drinking days from baseline, compared with a 26.4-percentage-point reduction in the placebo group. The difference between groups was statistically significant.
Note: A percentage point refers to the absolute difference between two percentages, rather than a relative percentage change.
- Lower overall alcohol consumption. Average alcohol consumption over 30 days decreased by approximately 1,550 grams of pure alcohol in the semaglutide group, compared with approximately 1,026 grams in the placebo group.
- Reduced alcohol craving. Participants receiving semaglutide also showed larger reductions in alcohol craving scores and greater improvements on standardized alcohol use questionnaires than those receiving placebo.
- Biomarker findings. Laboratory analyses were consistent with participants’ reported reductions in alcohol use. Blood concentrations of phosphatidylethanol (PEth), a biomarker associated with recent alcohol consumption, decreased in the semaglutide group but showed little change in the placebo group. Additional laboratory measures, including gamma-glutamyl transferase (GGT), also improved to a greater extent among participants receiving semaglutide.
2. Weight Changes
Participants treated with semaglutide lost an average of 11.2 kg, while those receiving placebo lost an average of 2.2 kg during the 26-week study. Average waist circumference, BMI, and HbA1c also decreased more in the semaglutide group.
3. Safety
The most commonly reported adverse events involved the gastrointestinal system and were generally mild to moderate and temporary. The most frequently reported side effects included:
- Nausea: 57% in the semaglutide group vs. 7% in the placebo group
- Reduced appetite: 35% vs. 15%
- Constipation: 35% vs. 17%
- Acid reflux: 28% vs. 2%
- Diarrhea, vomiting, and abdominal discomfort were also reported more frequently in the semaglutide group.
Four participants discontinued semaglutide because of adverse events. Serious adverse events were uncommon in both groups.
Authors’ Conclusions
The authors concluded that, within this randomized clinical trial, semaglutide was associated with greater reductions in heavy drinking days and several other alcohol-related outcomes than placebo among treatment-seeking adults with obesity and alcohol use disorder. They note that the findings are consistent with previous preclinical research, registry-based studies, and smaller clinical investigations suggesting that GLP-1 receptor agonists may influence alcohol-related behaviors.
One additional observation was the relationship between weight loss and changes in alcohol consumption. Participants who experienced greater weight loss also tended to show larger reductions in heavy drinking days. However, the authors emphasize that the study was not designed to determine why this relationship occurred. Because daily calorie intake was not measured, they note that further research will be needed to better understand the biological mechanisms underlying these findings.
The investigators also observed that reductions in alcohol consumption continued throughout the 26-week intervention, including after the gastrointestinal side effects commonly associated with semaglutide had generally subsided. According to the authors, this suggests that temporary nausea alone is unlikely to explain the observed changes in drinking behavior.
The authors also noted several limitations. Every participant in the trial had obesity, meaning it remains unknown whether similar findings would be observed in people with alcohol use disorder who do not have obesity. In addition, most participants identified as White, the study was conducted at a single research center, and follow-up ended after 26 weeks. The authors therefore recommend that larger clinical trials involving more diverse populations and longer observation periods be conducted before these findings can be generalized more broadly.
Understanding the Broader Context
Interest in GLP-1 receptor agonists has expanded rapidly in recent years because these medications influence biological systems involved in metabolism, appetite regulation, and reward processing. As a result, researchers have begun exploring whether these pathways may also be relevant to conditions beyond diabetes and obesity.
This clinical trial adds new evidence to that growing body of research by evaluating semaglutide in adults with both obesity and alcohol use disorder who were actively seeking treatment. Rather than focusing only on alcohol intake, the investigators also measured alcohol craving, laboratory biomarkers, body weight, and several additional clinical outcomes, providing a broader picture of the changes observed during the 26-week intervention.
Although these findings come from a single randomized clinical trial conducted in a specific patient population, they contribute to ongoing research in this area. As noted by the authors, additional studies will be needed to determine whether similar outcomes are observed in other groups and to further investigate the biological mechanisms involved.
Final Thoughts
This randomized, double-blind, placebo-controlled clinical trial found that participants receiving semaglutide experienced greater reductions in heavy drinking days and several other alcohol-related outcomes than participants receiving placebo over a 26-week period. The study also reported greater reductions in body weight together with changes in laboratory biomarkers associated with alcohol consumption.
According to the authors, these findings add to growing scientific evidence exploring the potential role of GLP-1 receptor agonists in alcohol use disorder. They also emphasize that additional randomized clinical trials involving broader populations and longer follow-up periods will be important for confirming these findings and evaluating their generalizability.
The information in this article is provided for informational purposes only and is not medical advice. For medical advice, please consult your doctor.
Reference
Klausen, M. K., Justesen, S. K., Pedersen, J. N., Rasmussen, L., Jensen, A., Jensen, M. E., Knorr, U. B., Bergmann, M. L., Holst, J. J., Hartmann, B., Koob, G. F., Benveniste, H., Volkow, N. D., Ekstrøm, C. T., Knudsen, G. M., Vilsbøll, T., & Fink-Jensen, A. (2026). Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. The Lancet, 407(10537), 1687–1698. https://doi.org/10.1016/S0140-6736(26)00305-3
