BACKGROUND: Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity.
METHODS: In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy. The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model. Analysis adhered to the intention-to-treat principle, and missing outcome data were addressed using multiple imputations. Safety was assessed in all treated patients. The trial is registered at ClinicalTrials.govNCT05895643, and is complete.
FINDINGS: From June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis. Overall, 88 participants (81%) completed the full intervention. Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes. Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.
INTERPRETATION: Semaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder and this trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder.
FUNDING: The Research Foundation, Mental Health Services (Capital Region of Denmark), the Novo Nordisk Foundation, the Novavi Foundation, the Hartmann Foundation, and the Augustinus Foundation.
| Discipline Area | Score |
|---|---|
| Psychiatry |  |
| Public Health | |
| Special Interest - Obesity -- Physician | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
Semaglutide is effective for patients with obesity and alcohol use disorder. Great news!
Good supportive evidence of current thought.
The co-occurrence of obesity and alcohol use disorder is prevalent and difficult to treat. As a geriatric psychiatrist, the findings of this study are surprising and exciting, potentially showing that semaglutide could be a novel and highly effective treatment for alcohol use disorder in patients with obesity. While the limited sample size motivates the need for replication studies, these findings have the potential to make a large clinical impact.
The evidence of the effectiveness of GLP-1 agonists for substance use disorders, particularly alcohol use disorder, is growing fast. This RCT goes in that direction.
This seems like a pretty big deal if confirmed by other studies.
This is the first randomized trial to demonstrate that semaglutide plus cognitive behavioral therapy is better than cognitive behavioral therapy alone at reducing alcohol intake among obese patients with alcohol use disorder. This confirms findings in the literature from anecdotal data and observational data.
