Glucagon-Like Peptide-1 Receptor Agonists: A Novel Indication for Substance Use Disorders?

Recent evidence suggests that Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs) can assist in alcohol and related substance use disorders (ASUD). GLP-1RAs act on the same receptor targets as native GLP-1, but last from several hours to a week, compared to the 1.5-5 minutes for naturally occurring GLP-1. These receptor targets are the GLP-1 G-protein coupled receptors. They are part of a large family of 800-1000 receptors that are present throughout the human body, but higher in concentration in the hypothalamus, brainstem, and the gastrointestinal tract. Four hundred sixty of the G-protein coupled receptors are in the olfactory system, mediating smell and taste. Mechanistically, GLP-1RAs reduce activity in the dopamine reward system. The observational literature demonstrates that GLP-1RAs mitigate the risk of hospitalizations associated with alcohol use disorder and other substance use disorders. Semaglutide and liraglutide reduced ASUD-related hospitalizations compared to other GLP-1RAs and standard previously prescribed ASUD pharmacotherapy. This review will detail the evidence supporting this.