Semaglutide shows promise as a potential alcohol use disorder medication
This article was first published in NIAAA Spectrum Volume 16, Issue 1.
Intramural scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA), and collaborators from The Scripps Research Institute, found that semaglutide reduces alcohol consumption and binge-like drinking in a rodent model of alcohol misuse. Published in the June 2023 issue of the journal JCI Insight, the study adds to growing preclinical evidence that the glucagon-like peptide-1 (GLP-1) system plays a role in alcohol and other substance use disorders, and that GLP-1 receptor agonists show potential for treating people with alcohol use disorder (AUD).
GLP-1 is a gut hormone that stimulates insulin secretion after eating, which promotes a feeling of fullness, helps to regulate blood sugar, and reduces hunger cravings. Semaglutide and other GLP-1 agonists—medications that bind to GLP-1 receptors and mimic their effects—are currently used as treatments for diabetes and obesity.
“Parts of the brain that drive eating behaviors overlap extensively with the drive to use alcohol or other substances,” explained Lorenzo Leggio, M.D., Ph.D., and Leandro Vendruscolo, Pharm.D., Ph.D., two of the senior authors of the study. They added that there is also overlap between the brain mechanisms that regulate overeating and those that contribute to the development and maintenance of substance use disorders, including AUD. Dr. Leggio is Chief of the joint NIDA/NIAAA Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section. He also serves as the NIDA Clinical Director and Deputy Scientific Director. Dr. Vendruscolo is Chief of the Stress and Addiction Neuroscience Unit, a joint laboratory of NIDA and NIAAA.
Previous rodent studies demonstrated that GLP-1 receptor agonists suppressed the rewarding effects of alcohol and reduced alcohol consumption. Dr. Leggio and his colleagues noted that, compared with other GLP-1 receptor agonists, semaglutide is more potent, has a higher affinity for its receptor, and is longer acting. Together, these characteristics make semaglutide a promising candidate for preclinical investigation and clinical translational studies in people with AUD.
In the current study, the researchers demonstrated that semaglutide reduced binge-like alcohol drinking in both male and female mice, and that the effect was dose-dependent (i.e., greater amounts of semaglutide led to greater reductions in binge alcohol intake). The researchers also tested semaglutide in rats that were made dependent on alcohol through long-term exposure to alcohol vapor. They found that semaglutide reduced alcohol intake in this animal model, again with no sex differences.
Dr. Leggio’s team concluded that “the present finding that semaglutide suppresses alcohol intake in different animal models of alcohol misuse provides compelling support for testing semaglutide in future clinical trials in people with AUD.”
Reference: Chuong V, Farokhnia M, Khom S, Pince CL, Elvig SK, Vlkolinsky R, Marchette RC, Koob GF, Roberto M, Vendruscolo LF, Leggio L. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023;8(12):e170671. PubMed PMID: 37192005