Glucagon-like peptide-1 receptor agonists and alcohol use disorders: An emerging unexpected beneficial effect

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of people living with type 2 diabetes mellitus (T2DM) and/or obesity. Numerous concordant animal and human studies suggest that GLP-1RAs could reduce the risk of addiction, especially alcohol use disorders (AUD). This comprehensive review aims at summarising the known effects of GLP-1RAs on AUD. An extensive literature search detected clinical (either observational or controlled) studies that investigated the prevalence and severity of AUD in obese/T2DM patients treated with GLP-1RAs compared with a control group. In seven observational cohort studies (12 paired data for comparisons), the prevalence of AUD was reduced by 35% (hazard ratio 0.65; 95% confidence interval 0.56-0.74) with GLP-1RA therapy when compared to no-GLP-1 therapy. The protection by GLP-1RAs concerned both incidence and recurrence of AUD. These positive human findings confirm preclinical data in rodents and monkeys. Some genetic, experimental and functional neuroimaging human studies also supported a potential role of the GLP-1 system in the alcohol-related reward process. Only two randomised controlled trials are available yet with inconclusive results, but several are ongoing to confirm the protective effect of semaglutide on AUD. Different neuronal and psychological mechanisms involving the reward pathways are proposed to explain the favourable findings reported with GLP-1RAs. In conclusion, available data from observational cohort studies showed a concordant and significantly reduced risk of AUD and alcohol consumption habits with GLP-1RA therapy. However, further studies are required before considering any indication of GLP-1RAs for the prevention or management of AUD.