REVIEW OF: Hendershot CS et al, JAMA Psychiatry 2025;82(4):395–405
STUDY TYPE: Phase 2 RCT

GLP-1 agonists are generating buzz for alcohol use disorder (AUD), but trial data have been sparse. This 9-week, double-blind trial tested once-weekly semaglutide in 48 adults with AUD.

Participants with AUD (mean age 40; 71% female) were randomized to receive either semaglutide or placebo. Dosing followed a standard titration: 0.25 mg/week for 4 weeks, then 0.5 mg/week for 4 weeks—half a typical diabetes dose and below obesity dosing. The medication’s effect was measured in a lab session where participants were given their preferred alcoholic beverage, then researchers recorded how much they drank and their peak breath alcohol levels. Real-world drinking and craving were also measured.

On the lab task, semaglutide was superior to placebo in reducing the amount of alcohol consumed and peak breath alcohol concentration. In the weekly data, semaglutide reduced drinks per drinking day, craving, and heavy drinking, though drinking days were unchanged.

Semaglutide was also linked to benefits beyond drinking. In a subgroup of smokers (n = 13), cigarettes per day decreased more with semaglutide. Weight dropped by about 5% (p < 0.001) but remained unchanged with placebo. Adverse effects were mild, with no serious treatment-related events.

CARLAT TAKE
This study, though small and of short duration, represents some of the first high-quality clinical trial data showing that GLP-1 agonists can help people with AUD cut down on their drinking. The results are encouraging, but the overall evidence base remains limited, so we don’t recommend using these medications as first line. However, if your patient has a comorbid indication, a GLP-1 agonist is worth considering.