The weight-loss drug also treats alcohol use disorder
STUDY: Klausen MK et al, Lancet 2026;407:1687–98
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Research Foundation Mental Health Services (Capital Region of Denmark), Novo Nordisk Foundation, Novavi Foundation, Hartmann Foundation, Augustinus Foundation
EVIDENCE GRADE: High (9/10)
Background
GLP-1 receptor agonists like semaglutide (Ozempic, Wegovy) act on brain’s reward pathways and appetite regulation, but so far the trials in alcohol use disorder have been disappointing. This one moves it forward.
The Study
- 108 patients with moderate-to-severe alcohol use disorder and obesity (BMI ≥30).
- Randomized for 6 months to once-weekly semaglutide 2.4 mg subcutaneously or placebo, both alongside cognitive behavioral therapy.
- Primary outcome = reduction in heavy drinking days.
Heavy drinking days fell 41% from baseline in the semaglutide group versus 26% with placebo. Total alcohol consumption dropped about 1,550 g/month with semaglutide versus 1,026 g with placebo. Craving scores, liver enzymes, and WHO risk drinking levels all favored semaglutide.
Effect sizes were in the moderate range (Cohen’s d = 0.57 for heavy drinking days). The number needed to treat for a two-level WHO risk reduction was 4.3 — better than the 7 or higher reported for FDA-approved medications. Weight loss averaged 11 kg with semaglutide versus 2 kg with placebo, and heavier weight loss correlated with greater drinking reductions.
Side Effects
Nausea (57% on semaglutide vs 7% on placebo), usually mild and transient. Four patients in the semaglutide group discontinued due to side effects.
Pancreatic risk: Asymptomatic amylase elevations in 4 patients on semaglutide.
Limitations
The placebo group had more dropouts, and the reason suggests functional unblinding. They figured out they were taking a placebo and dropped out to get real semaglutide from another source. Other limitations: Single-center, industry-funded, enrolled only patients with comorbid obesity, limiting generalizability to lower BMIs.
Practice Implications
- This study updates my scorecard on GLP-1’s and changes the bottom line.
- It’s time to start considering semaglutide for alcohol use disorder in patients with obesity.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
