Therapeutic Potential of the Novel GLP-1 Receptor Agonist Semaglutide in Alcohol Use Disorder

Abstract Alcohol use disorder (AUD) is a prevalent neuropsychiatric disorder with serious health and social consequences. However, few licensed and successful pharmacotherapies exist for heterogeneous and complex disorders such as AUD, and these are poorly utilized. Preclinical and clinical findings suggest that the glucagon-like peptide-1 (GLP-1) system, a gut-brain peptide, is involved in the neurobiology of addictive behaviors. Additionally, the GLP-1 receptor (GLP-1R) has become a promising target for the treatment of AUD. Semaglutide, a novel GLP-1R agonist, has received clinical approval to treat type 2 diabetes in both subcutaneous and oral dosage forms. Studies have shown that it significantly reduces alcohol consumption and relapse of alcohol addiction in rats, suggesting its potential effectiveness for treating alcohol abuse in humans, particularly in overweight patients with AUDs. However, the use of semaglutide is associated with potential risks, such as gallbladder disease and clinical complications associated with delayed gastric emptying. This review evaluates the safety of semaglutide to inform its wider clinical application. Further extensive and in-depth studies on semaglutide are needed to reveal additional valuable clinical benefits.