GLP-1 RECEPTOR AGONISTS AND ALCOHOL USE DISORDER: PROMISE FOR A NEW TREATMENT APPROACH
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5617Keywords:
Endocrinology, Addiction, Alcohol, Neurobiology, GLP-1Abstract
The role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as effective glucose-lowering and nephroprotective agents in type 2 diabetes is well established. Their emergence as treatments for obesity is considerably more recent. In the short time since this indication was approved, these medications have attracted considerable attention, and their use in clinical practise has expanded rapidly. Amid this rapid expansion, clinicians have encountered growing anecdotal reports from patients taking GLP-1RAs describing unexpected improvements in substance use behaviours. Such reports are consistent with a growing body of preclinical evidence demonstrating that GLP-1RAs reduce intake of alcohol and other addictive substances. Whether preclinical observations can be replicated in human studies is currently being tested in clinical trials. One prevailing hypothesis suggests that glucagon-like peptide-1 (GLP-1) exerts its effects via central mechanisms, including, at least in part, modulation of dopamine transmission. Studies imply that activation of central glucagon-like peptide -1 receptors (GLP-1Rs) functionally regulates the mesolimbic reward pathway and reduces addiction-like behaviors in rodent models. This narrative review summarizes the existing evidence regarding the effects of GLP-1RAs on alcohol consumption. Relevant studies published between January 2015 and March 2026 were identified via literature search. Collectively, the evidence supporting GLP-1RAs for the treatment of AUD is promising yet inconsistent, with randomized clinical trials yielding mixed results for the primary outcome of reduced alcohol consumption. Although current findings do not justify changes to clinical practice, they point toward potential benefits of GLP-1RAs, extending beyond glycemic and weight control, particularly among patients with AUD.
References
World Health Organization. (2024, June 25). Cada año fallecen más de tres millones de personas, sobre todo varones, debido al consumo de alcohol y drogas. https://www.who.int/es/news/item/25-06-2024-over-3-million-annual-deaths-due-to-alcohol-and-drug-use-majority-among-men
Witkiewitz, K., et al. (2019). Advances in the science and treatment of alcohol use disorder. Science Advances, 5(9), eaax4043. https://doi.org/10.1126/sciadv.aax4043
Ginley, M. K., Pfund, R. A., Rash, C. J., & Zajac, K. (2021). Long-term efficacy of contingency management treatment based on objective indicators of abstinence from illicit substance use up to 1 year following treatment: A meta-analysis. Journal of Consulting and Clinical Psychology, 89, 58–71. https://doi.org/10.1037/ccp0000552
Mateu-Mollá, J., Pérez-Gálvez, B., & Villanueva-Blasco, V. J. (2025). Pharmacological treatment for substance use disorder: A systematic review. Addictive Behaviors, 163, 108242. https://doi.org/10.1016/j.addbeh.2024.108242
Baggio, L. L., & Drucker, D. J. (2007). Biology of incretins: GLP-1 and GIP. Gastroenterology, 132(6), 2131–2157. https://doi.org/10.1053/j.gastro.2007.03.054
Hernandez, N. S., & Schmidt, H. D. (2019). Central GLP-1 receptors: Novel molecular targets for cocaine use disorder. Physiology & Behavior, 206, 93–105. https://doi.org/10.1016/j.physbeh.2019.03.026
Vallöf, D., et al. (2016). The glucagon-like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents. Addiction Biology, 21, 422–437. https://doi.org/10.1111/adb.12295
Herman, R. J., Hayes, M. R., Audrain-McGovern, J., Ashare, R. L., & Schmidt, H. D. (2023). Liraglutide attenuates nicotine self-administration as well as nicotine seeking and hyperphagia during withdrawal in male and female rats. Psychopharmacology, 240, 1373–1386. https://doi.org/10.1007/s00213-023-06376-w
Douton, J. E., et al. (2021). Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin-seeking behavior in rats. Behavioural Pharmacology, 32, 265–277. https://doi.org/10.1097/FBP.0000000000000609
Edvardsson, C. E., Cadeddu, D., Ericson, M., Adermark, L., & Jerlhag, E. (2025). An inhibitory GLP-1 circuit in the lateral septum modulates reward processing and alcohol intake in rodents. eBioMedicine, 115, 105684. https://doi.org/10.1016/j.ebiom.2025.105684
Vallöf, D., Kalafateli, A. L., & Jerlhag, E. (2019). Brain region specific glucagon-like peptide-1 receptors regulate alcohol-induced behaviors in rodents. Psychoneuroendocrinology, 103, 284–295. https://doi.org/10.1016/j.psyneuen.2019.02.006
Edvardsson, C. E. (2026). Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents. eBioMedicine, 124, 106119. https://doi.org/10.1016/j.ebiom.2025.106119
Aranäs, C., et al. (2023). Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. eBioMedicine, 93, 104642. https://doi.org/10.1016/j.ebiom.2023.104642
Krieger, J.-P., et al. (2016). Knockdown of GLP-1 receptors in vagal afferents affects normal food intake and glycemia. Diabetes, 65, 34–43. https://doi.org/10.2337/db15-0973
Hayes, M. R., Skibicka, K. P., & Grill, H. J. (2008). Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation. Endocrinology, 149, 4059–4068. https://doi.org/10.1210/en.2007-1743
Zhao, X., et al. (2021). GLP-1 receptor agonists: Beyond their pancreatic effects. Frontiers in Endocrinology, 12, 721135. https://doi.org/10.3389/fendo.2021.721135
Diz-Chaves, Y., Herrera-Pérez, S., González-Matías, L. C., & Mallo, F. (2022). Effects of glucagon-like peptide 1 (GLP1) analogs in the hippocampus. In G. Litwack (Ed.), Vitamins and hormones (pp. 457–478). Academic Press. https://doi.org/10.1016/bs.vh.2021.12.005
Chen, B., et al. (2024). GLP-1 programs the neurovascular landscape. Cell Metabolism, 36, 2173–2189. https://doi.org/10.1016/j.cmet.2024.09.003
Merchenthaler, I., Lane, M., & Shughrue, P. (1999). Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. Journal of Comparative Neurology, 403, 261–280. https://doi.org/10.1002/(sici)1096-9861(19990111)403:2%3C261::aid-cne8%3E3.0.co;2-5
Alvarez, E., Roncero, I., Chowen, J. A., Thorens, B., & Blázquez, E. (1996). Expression of the glucagon-like peptide-1 receptor gene in rat brain. Journal of Neurochemistry, 66, 920–927. https://doi.org/10.1046/j.1471-4159.1996.66030920.x
Cork, S. C., et al. (2015). Distribution and characterisation of glucagon-like peptide-1 receptor expressing cells in the mouse brain. Molecular Metabolism, 4, 718–731. https://doi.org/10.1016/j.molmet.2015.07.008
Schick, R. R., Zimmermann, J. P., vorm Walde, T., & Schusdziarra, V. (2003). Glucagon-like peptide 1-(7–36) amide acts at lateral and medial hypothalamic sites to suppress feeding in rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 284, R1427–R1435. https://doi.org/10.1152/ajpregu.00479.2002
McMahon, L. R., & Wellman, P. J. (1998). PVN infusion of GLP-1-(7–36) amide suppresses feeding but does not induce aversion or alter locomotion in rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 274, R23–R29. https://doi.org/10.1152/ajpregu.1998.274.1.R23
Abtahi, S., VanderJagt, H. L., & Currie, P. J. (2016). The glucagon-like peptide-1 analog exendin-4 antagonizes the effect of acyl ghrelin on the respiratory exchange ratio. NeuroReport, 27, 992–996. https://doi.org/10.1097/WNR.0000000000000650
Abtahi, S., et al. (2019). Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus. General and Comparative Endocrinology, 270, 75–81. https://doi.org/10.1016/j.ygcen.2018.10.008
Kalra, S. (2011). Change in alcohol consumption following liraglutide initiation: A real-life experience. 71st American Diabetes Association Conference, Poster 1029, 93.
Klausen, M. K., Thomsen, M., Wortwein, G., & Fink-Jensen, A. (2022). The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. British Journal of Pharmacology, 179(4), 625–641. https://doi.org/10.1111/bph.15677
Suchankova, P., et al. (2015). The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: Evidence from human genetic association studies and a mouse model of alcohol dependence. Translational Psychiatry, 5, e583. https://doi.org/10.1038/tp.2015.68
Klausen, M. K., et al. (2022). Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight, 7(19), e159863. https://doi.org/10.1172/jci.insight.159863
Probst, L., et al. (2023). Effects of dulaglutide on alcohol consumption during smoking cessation. JCI Insight, 8, e170419. https://doi.org/10.1172/jci.insight.170419
Hendershot, C. S., et al. (2025). Once-weekly semaglutide in adults with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 82, 395. https://doi.org/10.1001/jamapsychiatry.2024.4789
Wium-Andersen, I. K., et al. (2022). Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events: A nationwide register-based cohort and self-controlled case series study. Basic & Clinical Pharmacology & Toxicology, 131, 372–379. https://doi.org/10.1111/bcpt.13776
Wang, W., et al. (2024). Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nature Communications, 15, 4548. https://doi.org/10.1038/s41467-024-48780-6
Qeadan, F., McCunn, A., & Tingey, B. (2025). The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction, 120, 236–250. https://doi.org/10.1111/add.16679
Lähteenvuo, M., et al. (2025). Repurposing semaglutide and liraglutide for alcohol use disorder. JAMA Psychiatry, 82, 94–98. https://doi.org/10.1001/jamapsychiatry.2024.3599
Farokhnia, M., et al. (2025). Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake. Journal of Clinical Investigation, 135(9), e188314. https://doi.org/10.1172/JCI188314
O’Farrell, M., Almohaileb, F. I., & le Roux, C. W. (2025). Glucagon-like peptide-1 analogues reduce alcohol intake. Diabetes, Obesity and Metabolism, 27(3), 1601–1604. https://doi.org/10.1111/dom.16152
Quddos, F., et al. (2025). A preliminary study of the physiological and perceptual effects of GLP-1 receptor agonists during alcohol consumption in people with obesity. Scientific Reports, 15(1), 32385. https://doi.org/10.1038/s41598-025-17927-w
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Jakub Fidelus, Julia Czerniewska, Magdalena Filuk, Marianna Ciastoń, Mikołaj Dybicz, Olga Endler, Julia Mądrzak, Dominika Dutkiewicz, Klaudia Jurkowska, Marta Handzel

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

