GLP-1 Receptor Agonists for Treating Alcohol Use Disorder: A Critical Review

This narrative review evaluates glucagon-like peptide-1 receptor agonists (GLP-1RAs) as potential treatments for alcohol use disorder (AUD), a major public health problem with limited treatment options. We first briefly describe the development of GLP-1RAs for treating type 2 diabetes and obesity and then focus on recent studies of the drugs' effects on alcohol-related behaviors, both in animal models and clinical studies. We identified relevant literature by searching for studies of incretin-based therapies using PubMed, Google Scholar, and clinicaltrials.gov and reviewing the reference lists of published reviews. We limited our discussion of preclinical studies of alcohol-related effects to those that provide insights into the mechanism of effects. Clinical studies comprised both observational studies, including those using electronic health records and other real-world data, and randomized controlled clinical trials, including studies completed or in progress. Of the clinical studies, we include original, peer-reviewed research published in English and excluded case reports, commentaries, and preprints. This yielded a total of 13 preclinical studies, 14 clinical studies, 4 published interventional trials, and 19 interventional trials in progress or completed but unpublished. We found convergent evidence from animal and human studies that GLP-1RAs reduce alcohol consumption and improve alcohol-associated outcomes. Several randomized controlled trials (RCTs) in progress aim to test the effects of both established and novel compounds, and different drug formulations and combinations on alcohol consumption. Additional RCTs are needed to establish the efficacy of GLP-1RAs for treating AUD, with mechanistic studies needed to elucidate more fully their mode of action in reducing alcohol consumption.