A systematic review on the role of glucagon-like peptide-1 receptor agonists on alcohol-related behaviors: potential therapeutic strategy for alcohol use disorder

Feb 19, 2025Acta neuropsychiatrica

Glucagon-like peptide-1 receptor drugs and their possible role in treating alcohol use disorder

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Abstract

Nineteen preclinical studies indicate that GLP-1 receptor agonists (GLP-1RAs) can reduce alcohol-related behaviors.

GLP-1RAs, such as exenatide, show dose-dependent effects in reducing alcohol consumption in high alcohol-consuming models.
Semaglutide and liraglutide are associated with a decrease in alcohol intake, although their effects may be temporary.
In human studies, semaglutide significantly lowered alcohol consumption among individuals with alcohol use disorder.
Exenatide produced mixed results, reducing alcohol drinking primarily in individuals with high BMI.
Preclinical and clinical evidence suggests potential for GLP-1RAs as a treatment for reducing problematic drinking behaviors.

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INTRODUCTION: Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviours, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviours in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1's analogues interact with alcohol-related behaviours may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.

METHODS: A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviours were assessed.

RESULTS: Preclinical studies (= 19) indicate that GLP-1RAs attenuate alcohol-related behaviours, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (= 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations. n n

DISCUSSION: Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioural modifications in individuals living with alcohol use disorder.

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A systematic review on the role of glucagon-like peptide-1 receptor agonists on alcohol-related behaviors: potential therapeutic strategy for alcohol use disorder

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