Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled clinical trial
PubMed 42070571 · doi:10.1016/S0140-6736(26)00305-3
What was done
A 26-week, single-centre, randomised, double-blind, placebo-controlled trial evaluated subcutaneous once-weekly semaglutide (2.4 mg) versus placebo (saline) in 108 treatment-seeking adults (53 women, 55 men) with moderate to severe alcohol use disorder and comorbid obesity. Both groups received standard cognitive behavioural therapy. The primary endpoint was the reduction in the percentage of heavy drinking days at 26 weeks, analysed by intention-to-treat using an ANCOVA model with multiple imputation for missing data.
What was found
Eighty-eight participants (81%) completed the full trial. Semaglutide significantly decreased heavy drinking days (-41.1 percentage points from baseline, 95% CI -48.7 to -33.5) compared with placebo (-26.4 percentage points, 95% CI -34.1 to -18.6), yielding an estimated treatment difference of -13.7 percentage points (95% CI -22.0 to -5.4; p=0.0015). Semaglutide also had effects on secondary alcohol-related and somatic outcomes. Adverse events were primarily transient, mild-to-moderate gastrointestinal symptoms occurring more frequently in the semaglutide group.
Why it matters
This study provides randomized controlled trial evidence that GLP-1 receptor agonists can significantly reduce heavy drinking in individuals with alcohol use disorder and comorbid obesity.
Limits
The trial was conducted at a single centre with a modest sample size (n=108). Findings are restricted to treatment-seeking individuals with comorbid obesity receiving concurrent cognitive behavioural therapy, limiting generalisability to non-obese populations or broader clinical settings.
Cited by
- supports Animal studies, small trials, and opportunistic epidemiological studies show a pattern of semaglutide reducing alcohol consumption.