Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 42522065 · doi:10.1176/appi.ajp.20260003
What was done
In a phase 2, double-blind, parallel-arm randomized clinical trial, 50 treatment-seeking adults with moderate to severe alcohol use disorder (AUD) were randomized to receive oral semaglutide (escalated from 3 mg/day for 4 weeks to 7 mg/day for 4 weeks) or placebo for 8 weeks. The primary outcome was laboratory-based alcohol cue-elicited craving evaluated at week 6. Secondary and exploratory outcomes included heavy drinking days, drinks per day, drinks per drinking day, naturalistic alcohol craving, alcohol-related negative consequences, World Health Organization risk drinking level changes, and cannabis use days during the final 4 weeks of treatment.
What was found
Oral semaglutide did not significantly reduce the primary outcome of laboratory-assessed craving or drinks per day compared with placebo. However, semaglutide significantly reduced heavy drinking days (b=-0.580, 95% CI=-1.012 to -0.148), drinks per drinking day (b=-1.177, 95% CI=-2.307 to -0.047), naturalistic alcohol craving (b=-2.195, 95% CI=-4.174 to -0.216), cannabis use days (b=-1.434, 95% CI=-2.568 to -0.301), and alcohol-related consequences (b=-4.618, 95% CI=-8.651 to -0.585). Significantly more participants taking semaglutide reduced their risk drinking level by one or more levels compared with placebo (Wald chi-square = 4.01).
Why it matters
This trial provides randomized clinical evidence that oral GLP-1 receptor agonism can reduce heavy drinking, naturalistic craving, and alcohol-related harms in treatment-seeking individuals with moderate to severe AUD.
Limits
The study had a small sample size (n = 50), which limits statistical power and precision. The primary endpoint of laboratory cue-elicited craving and the secondary outcome of total drinks per day were not statistically significant. The intervention period was short (8 weeks) with a maximum oral dose of 7 mg/day, and safety outcomes, adverse events, and long-term durability following treatment cessation were not reported in the abstract.
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