Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial.
Level 2 - randomized trial
Individual double-blind randomized controlled trial
PubMed 39937469 · doi:10.1001/jamapsychiatry.2024.4789
What was done
A phase 2, double-blind, randomized, parallel-arm trial evaluated once-weekly subcutaneous semaglutide versus placebo over 9 weeks in 48 non-treatment-seeking adults with alcohol use disorder (AUD) at a single US academic medical center. Dosing was titrated weekly (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week). The primary outcome was laboratory alcohol self-administration measured before and after treatment at the 0.5 mg/week dose. Secondary and exploratory outcomes included prospective outpatient changes in drinking and craving.
What was found
Among 48 randomized participants (71% female; mean age 39.9 years), semaglutide significantly decreased alcohol intake during the laboratory self-administration task in grams consumed (β = -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (β = -0.46; 95% CI, -0.87 to -0.06; P = .03). Semaglutide showed no effect on average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (β = -0.41; 95% CI, -0.73 to -0.09; P = .04) and weekly alcohol craving (β = -0.39; 95% CI, -0.73 to -0.06; P = .01), while predicting greater reductions in heavy drinking over time (β = 0.84; 95% CI, 0.71 to 0.99; P = .04). In a subsample of individuals who smoked, semaglutide predicted greater reductions in cigarettes per day (β = -0.10; 95% CI, -0.16 to -0.03; P = .005).
Why it matters
This study provides initial randomized trial evidence in humans that GLP-1 receptor agonists can suppress alcohol intake, heavy drinking episodes, and craving in individuals with AUD.
Limits
The sample size was small (n = 48) and drawn from a single academic medical center. Participants were non-treatment-seeking, which limits generalizability to clinical populations seeking AUD therapy. The treatment duration was short (9 weeks) using low semaglutide doses, and several primary drinking frequency measures (average drinks per day, drinking days) showed no significant difference.
Cited by
- supports Published literature shows that GLP-1 receptor agonists reduce alcohol cravings.