Weight Loss Drug Curbs Alcohol Cravings, Consumption

Once-weekly subcutaneous injections of semaglutide (Ozempic, Novo Nordisk) reduced alcohol cravings and consumption in adults with alcohol use disorder (AUD), findings from a small phase 2 placebo-controlled trial showed.

The findings add to preclinical, observational, and pharmacoepidemiology evidence suggesting that the glucagon-like peptide 1 receptor agonist (GLP-1 RA) and similar medications may reduce alcohol intake and justify larger clinical trials to evaluate GLP-1 RAs for AUD, the investigators said.

“Should additional phase 2 and phase 3 clinical trials support repurposing one or more GLP-1 RAs for AUD, these treatments could have broad clinical infiltration, with potential to bypass many traditional impediments to the uptake of AUD medications, including low public and provider awareness and stigma toward AUD treatments,” lead author Christian Hendershot, PhD, with Keck School of Medicine, University of Southern California, Los Angeles, and coauthors wrote.

“Importantly, the increasing clinical uptake of GLP-1 RAs would presumably reduce prescribing barriers, including in primary care, where AUD treatments have proven difficult to bring to scale,” they added.

The study was published online on February 12 in JAMA Psychiatry.

Repurposing GLP-1s for AUD?

The study included 48 adults (mean age, 39.9 years) meeting criteria for AUD who were not seeking treatment. Over 9 weeks, they received once-weekly injections of semaglutide (0.25 mg/wk for 4 weeks, 0.5 mg/wk for 4 weeks, and 1.0 mg for 1 week) or placebo.

Participants recorded how much alcohol they drank over this period, and they also completed laboratory sessions at the beginning and end of the study period in which they could freely consume alcoholic drinks over 2 hours.

Compared with the placebo group, the group who had received low-dose semaglutide drank significantly less alcohol during the posttreatment laboratory session, with evidence of medium to large effect sizes for grams of alcohol consumed (P = .01) and peak breath alcohol concentration (P = .03).

Although the semaglutide and placebo groups did not differ in how often they drank alcohol during the study period (outside the lab), on days when they did drink alcohol, the semaglutide group drank less alcohol (P = .04) and reported less alcohol craving (P = .01) than the placebo group.

Semaglutide also led to greater relative reductions in cigarettes per day in a subsample of current smokers.

‘Exciting’ Results

“This is a small study, but an exciting one. It provides evidence that semaglutide treatment can reduce alcohol consumption, similar to how it has been shown to reduce food consumption and consequently body weight,” Stephen Burgess, PhD, with University of Cambridge, Cambridge, England, said in a statement from the UK Science Media Centre.

“The likely mechanistic pathway is by dampening brain cues that prompt an individual to crave both food and alcohol. It is currently unclear whether individuals who discontinue treatment will maintain healthy alcohol status posttreatment. Investigating this question will require larger and longer studies,” Burgess noted.

Also weighing in, Riccardo De Giorgi, MD, DPhil, with University of Oxford, Oxford, England, said the study was “small but sound and well-designed [and] looked at several outcomes of importance to alcohol misuse. It represents, at present, the most robust and yet preliminary piece of evidence suggesting that these medications may indeed be useful for the care of people with alcohol use disorder.”

Matt Field, BSc, DPhil, with University of Sheffield, Sheffield, England, noted that the study overcomes limitations of prior observational studies and demonstrates, “for the first time, a causal effect of semaglutide on the amount of alcohol that people drink. This study will hopefully serve as a springboard for further research.”

This research was supported by National Institute on Alcohol Abuse and Alcoholism. Hendershot, Burgess, De Giorgi, and Field had no relevant disclosures.