Semaglutide reduces alcohol and cigarette use in a randomised phase 2 study

Simon Collins HIV i-Base

GLP-1 receptor agonists (RAs) are now first-line therapy in US guidelines for the management of type-2 diabetes and are approved at higher doses for weight loss.

One potential mechanism of action for the dramatic weight reductions involves blocking the reward pathway in the brain, as anecdotally people lose interest in eating. This is supported by some study participants reporting a similar lack of interest in other addictive behaviour, for example reducing alcohol use.

Results from a nine-week, randomised (1:1), placebo-controlled phase 2 study, published in JAMA Psychiatry, report that weekly semaglutide significantly reduced some criteria for alcohol intake. Reduced use of cigarettes was also reported among smokers in the study. [1]

The study randomised 48 people with alcohol use disorder (AUD) who were not actively seeking treatment to either weekly subcutaneous injections of semaglutide or placebo. Low-dose semaglutide was given at 0.25 mg/week for weeks 1 to 4 and 0.5 mg/week for weeks 5 to 8. A final dose of 0.5 or 1.0 mg was given at week 9 to collect additional safety data.

Baseline characteristics included 71% women (34/48), 81% white, mean (SD) age was 39.9 (10.6) years and most had BMI >30 (n = 27) or 25.0 to 29.9 (n = 20).

Although semaglutide did not affect average drinks per calendar day or number of drinking days, it significantly reduced drinks per drinking day and greater reductions in heavy drinking (both p=0.04) together with weekly alcohol craving (p=0.01). The reduction in the number of cigarettes per day in smokers was also significant (p=0.005).

The authors commented on the importance of larger studies, given these results and the limited current options to treat AUD. They also concluded “given numerous GLP-1 receptor agonists at various stages of development future studies need not be limited to a single medication”.

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It is notable that this was an independent investigator study.

Novo Nordisk generally only runs studies for clinical indications related to alcohol use, including improving liver function rather than for addiction-related use.

This is important because of the potential for use when withdrawing from chemsex addictions, including crystal meth. [2]

Longer follow-up is also needed in the current study to see the impact of stopping semaglutide on both alcohol and cigarette use.

Reference

Hendershot CS et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. (12 February 2025).
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/jamapsychiatry.2024.4789

CROI 2024: HIV studies with semaglutide: significant benefits but limited access for treatment and research. HTB (10 March 2024).
https://i-base.info/htb/47286