Incretin Mimetics and Alcohol-Related Outcomes: A Structured Narrative Review.

Abstract

Harmful alcohol use results in negative health outcomes for millions of patients each year, with limited effective treatment options available for those diagnosed with alcohol use disorder (AUD). Incretin mimetics, such as glucagon-like-peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1RAs (GIP/GLP-1RAs), have garnered interest for their positive effects across a host of conditions beyond type 2 diabetes mellitus (T2DM); this includes substance use, where interactions between GLP-1, dopamine modulation, and other neuroinflammatory mechanisms suggest potential benefit. Accordingly, this structured narrative review details evidence related to the role of incretin mimetics for alcohol-related outcomes. Relevant pathophysiology is explored, as well as 21 observational and experimental clinical studies in this area. Literature suggests that incretin mimetics offer an opportunity for a shift in how medicine approaches AUD, leveraging multifaceted pathology to reduce alcohol consumption, craving intensity, health care utilization, and alcohol-related complications. However, substantial gaps remain in establishing their place in therapy as a pharmacotherapeutic option in AUD and understanding the nuanced role that these agents may offer to addiction medicine.