Written and Reviewed by Team Pharmacally
A recent study conducted by Dr. Christian Hendershot at University of North Carolina (UNC), Chapel Hill School of Medicine and published in JAMA Psychiatry aimed to evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and cravings in adults with alcohol use disorder (AUD). The findings suggest that semaglutide a GLP-1 receptor agonist may significantly decrease alcohol cravings and consumption in individuals with AUD. This breakthrough offers new possibilities for treating AUD, a condition that impacts millions of people around the globe.
Study Overview
The study was a phase 2, double-blind, randomized, parallel-arm trial that involved 9 weeks of outpatient treatment. It included 48 participants diagnosed with moderately severe Alcohol Use Disorder (AUD). Throughout the nine-week period, participants were randomly assigned to receive either semaglutide or a placebo. They received semaglutide at doses of 0.25 mg per week for the first 4 weeks, followed by 0.5 mg per week for the next 4 weeks, and then 1.0 mg for the final week, or a placebo during weekly clinic visits. To evaluate the drug’s effectiveness, researchers conducted controlled drinking self-administration sessions at both the start and end of the study, allowing participants to consume alcohol freely in a laboratory environment.
Key Findings
Participants who received semaglutide showed a notable decrease in alcohol consumption during their last drinking session compared to their first session, a trend that was not seen in the placebo group. In particular, those on semaglutide drank less alcohol than those in the placebo group. Furthermore, the semaglutide participants reported fewer days of heavy drinking and a reduction in their weekly cravings for alcohol.
Mechanism of Action and Role of GLP-1 agonist
Endogenous GLP-1 is generated through the cleavage of the prohormone proglucagon in the intestinal endocrine L cells and is released when food is consumed. It enhances insulin secretion, suppresses glucagon secretion, slows down gastric emptying, and curbs appetite. Additionally, GLP-1 is produced in the nucleus tractus solitarius (NTS) of the brain stem and acts as a neurotransmitter in various brain regions. GLP-1 receptors are found in areas of the brain thought to be linked to reward and addiction. Research in mice suggests that several GLP-1 receptor agonists can cross the blood-brain barrier to some degree when given systemically.
GLP-1 receptor agonists are now approved for treating diabetes and obesity. Research in rodents, monkeys, and human case reports indicates that these agonists may help lower alcohol consumption. Additionally, genetic differences in GLP-1R have been linked to a higher risk of alcohol use disorder (AUD) in people. A recent study from Denmark found that using GLP-1 agonists is associated with a temporary (3-month) decrease in the risk of future alcohol-related incidents.
Some studies suggest that GLP-1 receptor agonists (GLP-1RAs) can decrease alcohol-seeking behaviour and support individuals in maintaining self-denial, which may lead to lower relapse rates. Alcohol consumption is linked to liver disease, inflammation, and cardiovascular issues. GLP-1RAs may help protect the liver by reducing fat buildup and inflammation, and they could also mitigate alcohol-related neuroinflammation. In comparison to traditional medications for alcohol use disorder (AUD) such as naltrexone, acamprosate, and disulfiram, GLP-1RAs have a well-documented safety profile. They are not associated with significant abuse potential or major drug interactions.
Semaglutide, a GLP-1RA, is mainly prescribed for managing type 2 diabetes and obesity. It works by mimicking the GLP-1 hormone, which boosts insulin production, curbs appetite, and extends feelings of fullness. Researchers believe that these effects might also help reduce cravings for addictive substances, including alcohol, by affecting the brain’s reward pathways.
Hence GLP-1 receptor agonists show considerable potential as a new treatment option for alcohol use disorder, as they may lower alcohol consumption, cravings, and the risk of relapse, while also enhancing metabolic and liver health. More research is needed to determine their long-term effectiveness and best practices for use in treating AUD.
Alcohol Use Disorder
Alcohol Use Disorder (AUD) is a significant public health concern that impacts millions of individuals around the globe. According to the World Health Organization (WHO, 2023), harmful alcohol consumption is responsible for approximately 3 million deaths each year. In the United States, data from the National Survey on Drug Use and Health (NSDUH) indicates that in 2021, around 29.5 million people aged 12 and older (10.5%) were diagnosed with AUD. Current treatment options for AUD encompass behavioural therapies, pharmacological interventions, and support groups. However, these treatments have notable limitations: there are only three FDA-approved medications available (naltrexone, acamprosate, disulfiram), which often have limited effectiveness and adherence challenges. Many individuals do not respond well to these medications. Additionally, AUD is characterized by a chronic relapsing nature, with relapse rates estimated between 40-60% within a year of treatment. Managing triggers such as stress, social cues, and cravings continues to be a significant challenge. Interestingly, semaglutide, a GLP-1 receptor agonist typically used for diabetes and weight management, has emerged as a potential treatment for alcohol use disorder (AUD).
Implications and Future Research
While the findings are encouraging, the study’s small sample size and short duration highlight the need for additional research. Dr. Hendershot pointed out that larger and longer-term studies are essential to validate the efficacy and safety of semaglutide as a treatment for AUD. He also mentioned that existing FDA-approved treatments for AUD should continue to be the primary options until more extensive data is available. This study adds to the growing evidence that GLP-1 receptor agonists like semaglutide could be repurposed to tackle various substance use disorders. As research advances, these medications may provide new hope for those looking for effective addiction treatments
References
- Hendershot CS, Bremmer MP, Paladino MB, et al. Once-Weekly Semaglutide in Adults with Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. February 12, 2025. doi:10.1001/jamapsychiatry.2024.4789
- Lähteenvuo M, Tiihonen J, Solismaa A, Tanskanen A, Mittendorfer-Rutz E, Taipale H. Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder. JAMA Psychiatry 2025; 82(1):94–98.doi:10.1001/jamapsychiatry.2024.3599
- Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol. 2022 Feb; 179(4):625-641. doi: 10.1111/bph.15677. PMID: 34532853; PMCID: PMC8820218.
- Quddos, F., Hubshman, Z., Tegge, A. et al.Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. Sci Rep13, 20998 (2023). https://doi.org/10.1038/s41598-023-48267-25
5.Aranäs, Cajsa et al, Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats, eBioMedicine, Volume 93, 104642
- Meyer D. Glantz, Chrianna Bharat, et al, The epidemiology of alcohol use disorders cross-nationally: Findings from the World Mental Health Surveys, Addictive Behaviours, Volume 102, 2020, 106128, https://doi.org/10.1016/j.addbeh.2019.106128
- Treatment for Alcohol Problems: Finding and Getting Help, National institute of alcohol abuse and alcoholism. Available from https://www.niaaa.nih.gov/sites/default/files/publications/NIAAA_Treatment_Alcohol_Problems_Booklet.pdf
- Semaglutide Shows Promise in Reducing Cravings for Alcohol, Heavy Drinking, UNC School of Medicine, UNC Health, 12 Feb 2025
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