Searching for New Pharmacological Treatments of Alcohol Use Disorder (AUD): Focus on GLP-1 Receptor Agonists

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.