April 30, 2026

expert reaction to an RCT for semaglutide in patients with alcohol use disorder and comorbid obesity

A randomised controlled trial published in The Lancet looks at the use of semaglutide in patients with alcohol use disorder and comorbid obesity. 

Prof Ashwin Dhanda, Professor of Liver Medicine, University of Plymouth, said:

“The new report builds on a previous pilot study conducted by the team that demonstrated, in a sub-group analysis, a potential benefit of GLP-1 agonist treatment in people with alcohol use disorder and obesity. The present trial shows that people with moderate to severe alcohol use disorder and obesity had a significant reduction in heavy drinking days after 26 weeks of treatment with semaglutide compared to those who received placebo. The data is supported by secondary outcomes including total alcohol consumption, AUDIT score and alcohol biomarkers.

“While the study provides evidence of the benefit of GLP-1 agonists for the treatment of alcohol use disorder, there are several caveats that need to be considered:

1. The study was not double-blinded (although I appreciate the study team did the best they could without having a matched placebo) and was open to potential bias from the site staff. It required weekly visits to the research clinic, which may have impacted the participant’s alcohol use.
2. The study population was self-selected and may have been more motivated and likely to engage with treatment than other people with alcohol use disorder.
3. The intervention included 10 sessions of cognitive behavioural therapy to support alcohol reduction. In the real world, many healthcare systems e.g. NHS would not have access to such therapy. We do not know whether the treatment would work without it.

“In summary, this is a high quality RCT that shows effectiveness of semaglutide and cognitive behavioural therapy for the treatment of self-selected people with moderate to severe alcohol use disorder and obesity. It is the first effectiveness trial in this population. Further trials are needed to establish GLP-1 agonist effectiveness in a real-world patient population.”

Dr Marie Spreckley, Research Programme Manager, University of Cambridge, said:

“This is a well-conducted randomised controlled trial in a treatment-seeking population, which strengthens its clinical relevance. The study found that semaglutide led to a greater reduction in heavy drinking days than placebo over 26 weeks, with an estimated treatment difference of 13.7 percentage points (95% CI -22.0 to -5.4).

“However, this is a relatively small, single-centre study with 108 participants, and all participants received cognitive behavioural therapy alongside the intervention. This likely increased improvements in both groups, meaning the observed difference reflects the additional effect of the drug on top of standard care.

“The findings are promising, but important limitations remain. The study only included individuals with obesity, which limits generalisability, and there was no follow-up beyond the 26-week treatment period to assess whether reductions in alcohol use are sustained.

“Gastrointestinal side effects were more common with semaglutide, although they were generally mild to moderate and transient.

“Overall, this study provides encouraging early evidence for a potential new treatment approach for people with co-occurring obesity and alcohol use disorder, but larger and longer-term trials in more diverse populations are needed before this can inform routine clinical practice.”

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

“This well-conducted trial showed that 26 weeks of semaglutide treatment led to a marked reduction in the frequency of heavy drinking among people with alcohol use disorder who were also obese (with a BMI of 30 or higher). It goes beyond previous observational studies of GLP-1 agonists and provides some of the strongest evidence yet that these medications may help some people to reduce their alcohol consumption.

“There are still important gaps in our knowledge about the long-term effects of these drugs and who might benefit from them the most. In this study, there was no follow-up after semaglutide treatment had finished. This means that we do not know if people reverted to their previous heavy drinking behaviour once they stopped taking the medication, something that may be a real risk because other studies have shown that when people stop taking GLP-1 agonists, they regain a lot of the weight that they have lost. This may be because “Drugs such as Ozempic and Wegovy act like brakes on our appetite. When people stop taking them, they are essentially taking their foot off the brake” (1). A similar mechanism may be involved in the short-term effects of GLP-1 agonists on alcohol consumption, and studies with longer-term follow-up are needed to establish this. It’s notable that there is another well-established medication that can help people to reduce their drinking (naltrexone), and even for this drug, which has been available and well-studied for a long-time, the long-term benefits after people stop taking the drug are uncertain. 

“Another key question is whether beneficial effects of these drugs extend to all patients with alcohol use disorders and other addictions, a significant minority of whom are underweight. “

1-  https://www.cam.ac.uk/research/news/patients-regain-weight-rapidly-after-stopping-weight-loss-drugs-but-still-keep-off-a-quarter-of and https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00043-X/fulltext

‘Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial’ by Mette Kruse Klausen et al. was published in The Lancet at 23:30 UK Time on Thursday the 30^th of April 2026. 

DOI: 10.1016/S0140-6736(26)00305-3

Declared interests

Prof Ashwin Dhanda: “I am leading a clinical trial testing the efficacy of semaglutide to reduce alcohol use in people with alcohol use disorder and liver disease. Study drug and placebo is provided free of charge by the manufacturer (Novo Nordisk). The trial is funded by NIHR.”

Dr Marie Spreckley: “I have conducted research on GLP-1 receptor agonists in the context of weight management and nutrition. I have no direct involvement in this study.”

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