Searching for New Pharmacological Treatments of Alcohol Use Disorder (AUD): Focus on GLP-1 Receptor Agonists.
This review examines the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) — including exenatide, semaglutide, dulaglutide, and the dual GLP-1R/GIP-R agonist tirzepatide — as pharmacological treatments for alcohol use disorder (AUD). The authors synthesized data from preclinical rodent and non-human primate studies, registered clinical trials, observational/pharmacoepidemiologic studies, and social media reports. In animal models, multiple GLP-1RAs were found to reduce alcohol consumption, alcohol-seeking behavior, alcohol-induced locomotor stimulation, reward memory, and relapse drinking, while also appearing to blunt alcohol's activation of the mesolimbic dopamine system. In the limited available human data, clinical trials of exenatide, semaglutide, and dulaglutide reported reductions in alcohol consumption, and pharmacoepidemiologic studies observed decreased rates of alcohol-related events among AUD patients prescribed GLP-1RAs or tirzepatide. The authors conclude that the GLP-1 system appears to be involved in AUD-related processes and that GLP-1RAs represent a promising but still tentative treatment avenue. Key limitations include the small number of human trials, heterogeneous study designs, and reliance on observational data for most clinical findings.
Why this grade: This is a narrative review synthesizing preclinical, observational, and limited clinical trial data; it does not itself generate primary human evidence, so an overall grade of "review" is most appropriate.
Alcohol use disorder (AUD) remains a crucial public health challenge worldwide. The currently available medications for AUD remain limited in the number and efficacy, meaning that the development of new treatments is of critical importance. Agonists of glucagon-like peptide-1 receptor (GLP-1RAs) have recently received attention as a potential anti-addiction treatment, particularly in AUD. This review presents data from preclinical studies in rodents and non-human primates, registered clinical trials, observational studies, and social media posts, investigating the effects of GLP-1RAs on alcohol-related behaviors and consumption. Several GLP1-RAs and tirzepatide (a dual agonist of GLP-1R and glucose-dependent insulinotropic polypeptide receptor; GIP-R) reduced alcohol consumption and alcohol-seeking behaviors, alcohol-induced locomotor stimulation and memory of alcohol reward, and suppressed relapse drinking in rodents. In addition, they prevent acute alcohol from activating the mesolimbic dopamine system. There are limited human data on the role of the GLP-1 system in AUD. In registered clinical trials, exenatide, semaglutide, and dulaglutide reduced alcohol consumption. Pharmacoepidemiologic studies documented a decreased risk of alcohol-related events in AUD patients using various GLP-1RAs and tirzepatide. Together, existing preclinical and clinical data suggest that GLP-1 is involved in the AUD process and imply the role of GLP1-RAs as a tentative treatment for AUD.
Educational summary of published research — not medical advice. License: cc by. Full text is shown only where licensing permits.