A RANDOMISED clinical trial has found that low-dose semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, reduces alcohol craving and some measures of alcohol consumption in adults with alcohol use disorder (AUD), supporting the need for larger trials to explore its potential as a treatment.
Alcohol use disorder is a chronic condition characterised by excessive alcohol consumption and cravings, often leading to significant health and social consequences. Preclinical and observational studies have suggested that GLP-1 receptor agonists, commonly used for weight loss and diabetes management, may also reduce alcohol intake. This phase 2 double-blind trial aimed to evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with AUD.
The trial enrolled 48 non-treatment-seeking participants with AUD, 71% of whom were female, with a mean age of 39.9 years. Participants were randomly assigned to receive either semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo over nine weeks of outpatient treatment. The primary outcome was laboratory-measured alcohol self-administration before and after treatment, while secondary outcomes included changes in weekly alcohol consumption and craving.
Semaglutide significantly reduced post-treatment alcohol consumption during the laboratory task, with medium to large effect sizes for grams of alcohol consumed (β = −0.48; P = .01) and peak breath alcohol concentration (β = −0.46; P = .03). While it did not affect average daily drinks or the number of drinking days, semaglutide significantly reduced drinks per drinking day (β = −0.41; P = .04) and weekly alcohol craving (β = −0.39; P = .01). It also predicted greater reductions in heavy drinking over time compared to placebo (β = 0.84; P = .04). Additionally, in participants who smoked cigarettes, semaglutide was associated with a significant reduction in cigarettes per day (β = −0.10; P = .005).
These findings suggest that semaglutide could be a promising treatment for AUD by reducing cravings and certain drinking behaviours. For clinical practice, this raises the possibility of repurposing GLP-1 receptor agonists for addiction management. Larger trials are needed to confirm these results and explore the long-term efficacy and safety of semaglutide in this context.
Katrina Thornber, EMJ
Reference
Hendershot CS et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2025;DOI:10.1001/jamapsychiatry.2024.4789.
