Clinical Question: Can GLP-1 receptor agonists be used to reduce alcohol use in obese patients motivated to reduce alcohol consumption?
Background: Alcohol use disorder accounts for 2.6 million deaths worldwide annually, and while some medications are approved for treatment, there is a need for new therapeutic interventions. Preclinical and initial human studies note that the GLP-1 receptor agonist semaglutide might reduce alcohol use.
Study Design: Randomized, single-center, double-blinded, placebo-controlled, clinical trial
Setting: Mental Health Center Copenhagen, Copenhagen, Denmark
Synopsis: The study enrolled 108 treatment-seeking adults with a BMI of 30 kg/m² or higher and an Alcohol Use Disorders Identification Test (AUDIT) score above 15. Eligibility also required at least six heavy drinking days within 30 days before enrollment. Participants were randomized 1 to 1 to once-weekly subcutaneous semaglutide titrated to 2.4 mg (n=54) or placebo (n=54) for 26 weeks. All participants in both groups were offered standardized cognitive behavioral therapy, and the mean number of sessions received was similar between arms. Heavy drinking days fell by 41.1 percentage points with semaglutide (95% CI, –48.7 to –33.5) versus 26.4 percentage points with placebo (95% CI, –34.1 to –18.6), an estimated treatment difference of –13.7 percentage points (95% CI, –22.0 to –5.4; P=0.0015). Total alcohol consumption also declined more with semaglutide (–1550.2 g versus –1025.9 g per 30 days; estimated difference –467.5 g per 30 days). Self-reported drinking was corroborated by phosphatidyl ethanol, an objective alcohol biomarker, which fell significantly with semaglutide but was unchanged with placebo. Only three medications—disulfiram, acamprosate, and naltrexone—are currently U.S. Food and Drug Administration-approved for alcohol use disorder, and these results suggest that semaglutide may add to that limited armamentarium in patients with comorbid obesity, though the authors caution that further research is needed before off-label use can be endorsed. Limitations include no follow-up beyond 26 weeks, restriction to patients with obesity, a predominantly white study population, and an inability to determine whether the treatment effect is independent of weight loss.
Bottom Line: Once-weekly semaglutide reduces heavy drinking days and total alcohol consumption in treatment-seeking patients with alcohol use disorder and comorbid obesity.
Citation: Klausen MK, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. Lancet. 2026;407(10540):1687-1698. https://doi.org/10.1016/S0140-6736(26)00305-3.
Dr. Lubin
Dr. Lubin is a PGY-3 internal medicine resident at the University of Tennessee Health Sciences College of Medicine and Erlanger Hospital, both in Chattanooga, Tenn.