February 12, 2025

expert reaction to study looking at once-weekly semaglutide in adults with alcohol use disorder

A study published in JAMA Psychiatry looks at the use of semaglutide in adults with alcohol use disorder. 

Prof Felicity Gavins, Professor of Pharmacology at Brunel University of London, and Royal Society Wolfson Fellow.

Is this good quality research?  Are the conclusions backed up by solid data?

“The research study used a robust phase 2, double-blinded, randomised design with appropriate statistical methods.  The findings show medium to large effect sizes for the key outcomes, but a small sample size was used so some caution is needed.”

How does this work fit with the existing evidence?

“This is the first controlled trial showing GLP-1RAs potential efficacy in humans with alcohol use disorder.  The data builds on preclinical and observational evidence that links GLP-1RAs to reduced alcohol intake.”

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“Yes, confounders have been in part controlled through randomisation, blinding and baseline adjustments.  However, there are limitations in that a small homogenous sample has been used and the trial was of a short duration.

What are the implications in the real world?  Is there any overspeculation?

“This study certainly provides promise for GLP-1RAs to reduce alcohol use.  However, claims regarding the widespread clinical impact and smoking cessation effects may be premature without larger long-term studies.”

Dr Survjit Cheeta, Reader in Psychology, Brunel University of London, said:

“In this study, scientists used the gold standard of evaluating a new medical treatment – a double-blind randomised control trial.  It means that the people who took part in the study were randomly allocated to either the treatment drug Semaglutide or placebo (a fake drug).  Neither the researchers involved in the study or the people who took part in the study were told what treatment they were getting until the end of the study.  This minimises bias.

“People often do not know that the legal drug alcohol actually results in the greatest harm to society through its involvement for example in road traffic accidents or domestic violence.  So the current findings that a low dose of the drug Semaglutide can reduce alcohol consumption especially in laboratory tests brings exciting new promise for better treatments for problem drinking and alcohol addiction.  This study emphasises the need for more research into the effects of incretin therapies (hormones that reduce blood glucose levels) for people with serious alcohol problems so as to reduce alcohol related harms.  Important ethical issues also need to be considered such as when and in whom should these medicines be used and how will they work in real life settings where many things influence drinking such as stress, walking past our favourite pub, being with our drinking buddies or the role of peer pressure especially in young people.”

Prof Anders Fink-Jensen, Professor, and Chief Physician, Psychiatric Center Copenhagen, Frederiksberg Hospital, Denmark, said:

“This is an interesting study – the first RCT investigating the effects of the GLP-1 RA semaglutide on alcohol consumption in AUD patients.  48 non–treatment-seeking participants with AUD were randomized to 9 weeks of treatment with semaglutide or placebo.  Participants in the semaglutide arm received semaglutide (0.25mg/week for 4 weeks, 0.5mg/week for 4 weeks, and 1.0mg for 1 week) or placebo at weekly clinic visits.

“Semaglutide treatment did neither affect average drinks per calendar day nor number of drinking days, but significantly reduced drinks per drinking day and weekly alcohol craving relative to placebo.

“As mentioned by the authors, some limitations exist: The study have a modest sample size, short treatment duration and did not reach steady state at a dose of 1 mg s.c., all reflecting the phase 2 stage of this trial.  Another limitation is the moderate level of AUD severity of this sample.  Therefore, larger and longer lasting trial data with higher doses of semaglutide is awaited.  However, it is still fascinating that clinical RCT data on the effects of semaglutide in AUD patients are starting to be available.”

Dr Stephen Burgess, Group Leader at the MRC Biostatistics Unit, University of Cambridge, said:

“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.  The likely mechanistic pathway is by dampening brain cues that prompt an individual to crave both food and alcohol.

“Limitations of this study include the small sample size and limited length of follow-up.  A key difference between weight loss and alcohol use is that the aim of weight loss treatment is to lose weight and then maintain a healthy weight.  Individuals will continue to eat food during and after treatment, and they will maintain a healthy weight if they maintain a calorie balance post treatment.  Whereas the aim with alcohol use disorder treatment is to reduce alcohol consumption, in many cases to zero, and then to maintain low or zero consumption.  It is currently unclear whether individuals who discontinue treatment will maintain healthy alcohol status post treatment.  Investigating this question will require larger and longer studies.  However, this study serves as an initial indication that semaglutide and similar weight loss drugs may be beneficial for treating alcohol use disorder, at least in the short term.”

Dr Riccardo De Giorgi, Clinical Lecturer at the Department of Psychiatry, University of Oxford, said:

“There has been much sensation (and even more noise) about GLP-1 drugs such as semaglutide in the medical field, especially regarding mental health.  However, their potential use as a mechanistically novel treatment for addiction is perhaps one of the most promising research avenues.  This investigator-initiated phase 2 randomised, placebo-controlled trial was small (48 people) but sound and well-designed.  It 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 – an extremely disabling condition. Semaglutide appeared to be safe and well-tolerated, though it should be noted that the administered dose was not large (0.5mg) and it was given over a relatively short period of time (8 weeks). This is the kind of study of which we need to see more if we are to see progress in this key research area.”

Prof Matt Field, Professor of Psychology, University of Sheffield, said:

“Some recent research suggests that semaglutide can reduce alcohol consumption in people with alcohol use disorders.  Those studies were observational, which means it is difficult to attribute the reduction in alcohol consumption to semaglutide rather than to confounding factors.  The present study overcomes these limitations by randomising adults with alcohol use disorder to receive weekly injections of either low-dose semaglutide or placebo over 9 weeks.  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 consume alcoholic drinks.  The research team found that, compared to the placebo group, the group who had received semaglutide drank significantly less alcohol in the lab.  Furthermore, 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 than the placebo group.

“Overall, this randomised study goes beyond previous observational studies which tended to look at people who were prescribed semaglutide for other reasons (usually diabetes) and evaluate how the drug affected their alcohol consumption.  With those types of observational studies, it is difficult to know if any effects on alcohol consumption were attributable to the drug or to confounding factors.  This study overcomes those limitations by demonstrating, 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.  Furthermore, the nature of the semaglutide effect (reducing the amount of alcohol consumed, whilst having no effect on the number of days that people drank alcohol) is consistent with the idea that semagludide reduces the reward or pleasure that people get from drinking alcohol, which is why they drink less.

“Some limitations of the study include the characteristics of the sample, who were not seeking treatment and were not motivated to reduce their alcohol consumption or stop drinking.  Most new treatments for alcohol use disorder are evaluated in people who ask for treatment because they want help to stop drinking altogether or reduce their drinking, so it will be important to test the effects of semaglutide on people with these characteristics.  A cautionary tale is that, when promising medications are tested in people with alcohol use disorder who are trying to cut down their drinking, we often see a large placebo response (i.e. a reduction in drinking among people taking placebo), which can obscure any additional effect of the drug.  Other considerations are that participants in this study had a body mass index (BMI) of at least 23, and most had a BMI of 30 or higher (which is in the obese range).  It will be important to establish if semaglutide can also reduce alcohol consumption in people who are not obese, particularly given that many people who seek treatment for alcohol problems are underweight.  This study had a small sample size and a short follow-up period, so it will be important to see if the effects of semaglutide are maintained over a longer time period, and, crucially, what happens when people stop taking the medication.  It will also be important to consider if and how semaglutide can be incorporated into conventional treatment for alcohol use disorder which might include detoxification, counselling or talking therapies, other types of medications, and involvement with mutual aid groups such as alcoholics anonymous.”

‘Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial’ by Christian S. Hendershot et al. was published in JAMA Psychiatry at 16:00 UK time on Wednesday 12 February 2025. 

DOI: 10.1001/jamapsychiatry.2024.4789

Declared interests

Prof Felicity Gavins: “No conflicts of interest.”

Dr Survjit Cheeta: “I can confirm that there is no conflict of interest.”

Prof Anders Fink-Jensen: “A.F.-J. has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1R stimulation on metabolic disturbances in patients with schizophrenia treated with antipsychotics and serves on an advisory panel for Novo Nordisk (no honorarium).”

Dr Stephen Burgess: “No relevant conflict of interest to declare

Dr Riccardo De Giorgi: “I am supported by the NIHR Oxford Health Biomedical Research Centre and currently conduct research on GLP-1 medications (NIHR OH BRC funded; no industry or any other kind of funding).”

Prof Matt Field: “I have no conflicts of interest to declare.”