Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial.

Summary

In a 26-week, single-centre, double-blind RCT (n=108), once-weekly semaglutide 2.4 mg significantly reduced heavy drinking days versus placebo (estimated treatment difference −13.7 percentage points; 95% CI −22.0 to −5.4; p=0.0015). Benefits extended to multiple secondary alcohol-related and somatic outcomes, with mostly mild-to-moderate transient gastrointestinal adverse events occurring more often with semaglutide.

Key Findings

• Once-weekly semaglutide reduced heavy drinking days more than placebo (−41.1 vs −26.4 percentage points from baseline; treatment difference −13.7; 95% CI −22.0 to −5.4; p=0.0015).
• Improvements were observed across multiple secondary alcohol-related and somatic outcomes.
• Adverse events were mostly mild-to-moderate gastrointestinal events and more frequent with semaglutide; 81% of participants completed the intervention.

Clinical Implications

Semaglutide may be considered as an adjunct to behavioral therapy for alcohol use disorder in patients with comorbid obesity, pending confirmation in multicentre trials and across BMI strata. Monitoring for gastrointestinal adverse events is warranted.

Limitations

• Single-centre study with a modest sample size (n=108), potentially limiting generalisability
• Restricted to patients with comorbid obesity and 26-week follow-up; longer-term efficacy and broader applicability remain to be established

Future Directions

Conduct multicentre, larger RCTs across BMI ranges; compare with current pharmacotherapies (e.g., naltrexone, acamprosate); evaluate long-term relapse, quality of life, and mechanistic biomarkers.