Sober Synthesis

This post is a brief review of a recent clinical trial investigating the use of the GLP-1 agonist Ozempic (semaglutide, Novo Nordisk) for treatment of alcohol use disorder.  The basic science, preclinical and early observational studies have been discussed in an earlier post here

The study was published in the January 15, 2025 issue of JAMA Psychiatry.  It is the first RCT using a GLP-1 agent in subjects meeting DSM-5 criteria for AUD. 

The study was a single center placebo controlled randomized clinical trial.  A total of 48 non-treatment seeking subjects meeting criteria for AUD were recruited.

Subjects were between the ages of 21-65.  78% were female.

The trial lasted nine weeks.  Each participant was given a weekly 0.25mg IM injection for the first 4 weeks and 0.5mg for weeks 4-8.  A single 1.0mg dose was given at week 9 prior to the final laboratory portion of the study.

The study used a hybrid protocol.  Subjects recorded baseline alcohol consumption, weekly consumption measures included average drinks per day, number of drinking days, number of heavy drinking days, and craving score.

The second portion looked at amount of alcohol consumed in a human laboratory setting along with breath alcohol concentration.

Mean percent change in drinks per drinking day weeks 1-4 and 4-8.  Significant drops at both doses with approximately 30% decrease with 0.5mg.  This is half of the normal dose used for diabetes.  Blue = Semaglutide subjects.

On the right breath alcohol concentration during the drinking period is compared pre and post treatment.

This is an infographic summarizing key points and findings for this study. 

Despite availability if the three medications FDA approved for treatment of AUD less than 2% of individuals receive pharmacotherapy for this indication.  Naltrexone and acamprosate have demonstrated only mild to moderate effect size in clinical studies.  This study found larger degree in all measures except for number of drinking days in the test subjects. 

The study limited selection to subjects with AUD not seeking treatment.  This is important as results are more likely due to drug effect rather than motivation to stop or limit consumption.  It is also significant that improvement was seen with lower doses than commonly used for diabetes treatment.  There is already off label use for AUD treatment so there is a need for studies such as this one.

This was a small single center level 2 clinical trial strongly supporting larger multi center studies

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Hendershot CS, Bremmer MP, Paladino MB, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. Published online February 12, 2025. doi:10.1001/jamapsychiatry.2024.4789

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2829811?guestAccessKey=5def1990-2a00-4771-8c9e-e19711b10db9&utm_source=for_the_media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=021225

These folks have been monitoring ongoing news and research on these and other medications to treat addiction.

https://recursiveadaptation.com/

JK 3/2025

For education and information purposes only.  This post should not be considered medical or professional advice.