GLP-1 receptor agonists: a novel therapeutic approach for alcohol use disorder?

Introduction

Alcohol use disorder (AUD) is a chronic and relapsing condition characterized by compulsive heavy alcohol consumption, along with impaired control over alcohol intake. AUD constitutes a significant global health burden, affecting around 280 million people worldwide, and contributes to significant morbidity, including cardiovascular complications, liver disease, and other psychiatric disorders. [1]

Existing pharmacological treatments for AUD, such as naltrexone and acamprosate, have shown only modest effectiveness. The response rates, defined as the proportion of patients who achieve abstinence or a meaningful reduction in heavy drinking, are often below 50%. [2] It is estimated that 45%–90% of patients receiving AUD treatment relapse within the first 3 years. [1] The limited number of available therapies and their variable outcomes have driven the search for new treatment approaches, with the glucagon-like peptide-1 receptor (GLP-1R) emerging as a promising molecular target. [2]

GLP-1 receptor agonists (GLP-1 RAs), including semaglutide, liraglutide, and dulaglutide, as well as dual agonists like tirzepatide, are primarily prescribed for type 2 diabetes mellitus (T2DM) and obesity due to their roles in regulating glucose metabolism and appetite. Recent preclinical studies have suggested that GLP-1 RAs may modulate reward pathways, decreasing alcohol-seeking behaviour in animal models through their actions on the mesolimbic dopamine system. Growing clinical evidence supports these findings, as observational studies report fewer alcohol-related events among patients receiving GLP-1 RAs for T2DM or obesity. Furthermore, randomised controlled trials (RCTs) have begun to assess their impact on AUD populations, indicating potential reductions in both alcohol consumption and craving. [2]

Objectives

This review aims to evaluate the effects of GLP-1 RAs on alcohol-related outcomes in adults with AUD.

Methods

A narrative review of the literature available on the platform PubMed was conducted.

Results

Findings differ according to study design. RCTs provide only limited support for reductions in alcohol consumption and craving. The limited statistical power and short durations of RCTs may explain the lack of significance. Conversely, observational studies consistently report an association between GLP-1 receptor agonist use and lower rates of alcohol-related events, particularly in chronic AUD outcomes.

The clinical implications are promising, particularly for patients with AUD and comorbid metabolic conditions like obesity or type 2 diabetes mellitus, where GLP-1 RAs are already indicated. However, confirmation through ongoing, well-controlled trials is still required to strengthen the evidence base. In the meantime, established evidence-based treatments for AUD, such as naltrexone and acamprosate, should continue to be used as first-line therapies until more conclusive data on GLP-1 receptor agonists become available. [2]

Conclusions

An expanding body of evidence suggests that the GLP-1 system plays a role in regulating alcohol-seeking behaviour and intake, indicating that GLP-1 RAs could serve as promising pharmacological treatments for AUD. However, robust conclusions cannot yet be drawn, as larger, well-designed randomized controlled trials with longer follow-up periods are needed before these agents can be recommended for routine clinical use in this setting.

References

1 - Klausen MK, Knudsen GM, Vilsbøll T, Fink-Jensen A. Effects of GLP-1 receptor agonists in alcohol use disorder. Basic Clin Pharmacol Toxicol. 2025;136(3):e70004. doi:10.1111/bcpt.70004. 2 - Sinha B, Ghosal S. The effects of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on alcohol-related outcomes: a systematic review and meta-analysis. Addict Sci Clin Pract. 2026;21:8. doi:10.1186/s13722-025-00637-z.