A recent randomized clinical trial published in JAMA Psychiatry provides promising evidence that semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, may help reduce alcohol consumption and craving in adults with alcohol use disorder (AUD).
Study Design and Participant
This phase 2, double-blind trial enrolled 48 non-treatment-seeking adults with AUD at an academic medical center. Participants were randomized to receive either:
-
Semaglutide (n=24): 0.25 mg/week for 4 weeks, then 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week
- Placebo (n=24)
The study lasted 9 weeks, with a final assessment at week 101.
Key Findings
Laboratory Alcohol Self-Administration
Semaglutide significantly reduced alcohol consumption during a posttreatment laboratory self-administration task compared to placebo:
- Grams of alcohol consumed: β = -0.48 (95% CI, -0.85 to -0.11; p = 01)
- Peak breath alcohol concentration: β = -0.46 (95% CI, -0.87 to -0.06; p = .03)
These effects showed medium to large effect sizes.
Weekly Alcohol Consumption
Over the 9-week treatment period, semaglutide:
- Significantly reduced drinks per drinking day (β = 0.41; 95% CI, -0.73 to -0.09; p = .04)
- Led to greater reductions in heavy drinking days over time compared to placebo (β = 0.84; 95% CI, 0.71 to 0.99; p = .04)
- Did not significantly affect average drinks per calendar day or number of drinking days.
Alcohol Craving
Semaglutide significantly reduced weekly alcohol craving compared to placebo (β = -0.39; 95% CI, -0.73 to -0.06; p = .01).
Effect on Cigarette Use
In a subgroup of current cigarette smokers (n=13), semaglutide treatment predicted greater reductions in cigarettes per day over time compared to placebo (β = -0.10; 95% CI, -0.16 to -0.03; p = .005).
Safety and Tolerability
Mean weight loss in the semaglutide group was 5%.
Adverse effects were mostly mild.
No serious adverse events or treatment-related discontinuations occurred.
Clinical Implications
This study provides initial evidence that low-dose semaglutide can reduce alcohol craving and some drinking outcomes in adults with AUD. The effect sizes observed, particularly at the 0.5 mg/week dose, were notably large compared to existing FDA-approved AUD medications.
The potential for GLP-1 receptor agonists to reduce both alcohol and cigarette use is particularly promising, given the frequent co-occurrence of these behaviors and their substantial health impacts.
While encouraging, these results should be interpreted cautiously given the study's limitations, including its small sample size, short duration, and use of only low doses of semaglutide. Larger, longer-term trials are needed to confirm these findings and establish the optimal dosing and safety profile of semaglutide for AUD treatment.
Nevertheless, this study justifies further investigation of GLP-1 receptor agonists as a potential new class of medications for AUD, which could help address the significant treatment gap in this common but undertreated condition.
Reference:
Hendershot CS et al. JAMA Psychiatry. Epub ahead of print. Abstract