Semaglutide and Alcohol use Disorder: Breaking Free of Addiction?

Alcohol use disorder (AUD) is a chronically relapsing disorder characterized by a compulsive alcohol drinking pattern, loss of control over intake, and the emergence of negative emotional states promoting alcohol dependence. It is unquestionably a major public health issue worldwide and a highly stigmatized condition. Unfortunately, AUD remains untreated in a significant number of adults. Since the approval of disulfiram by the FDA in 1951, only two medications (naltrexone and acamprosate) have gained subsequent FDA approval for this disorder. However, even when these medications are administered, the rates of treatment failure and/or relapse after withdrawal remain high. Novel therapeutic approaches are urgently needed to break down the barriers to AUD therapy and achieve positive long-term results. Glucagon-like peptide-1 (GLP-1) is produced by the preproglucagon-containing neurons of the brain, while GLP-1 receptors (GLP- 1Rs) are found in several areas of the central nervous system that govern many natural rewards. This paper discusses the current treatment landscape for individuals with AUD and the pathophysiological background supporting the administration of GLP-1R agonists in this setting. It explores in detail all preclinical and clinical evidence on semaglutide and its future perspectives as a therapeutic approach in individuals with AUD.