GLP-1 Receptor Agonists for Treating Alcohol Use Disorder: A Critical Review.
This narrative review evaluates the emerging evidence for glucagon-like peptide-1 receptor agonists (GLP-1RAs) — a drug class established for type 2 diabetes and obesity — as potential treatments for alcohol use disorder (AUD), a condition with currently limited pharmacological options. The authors searched PubMed, Google Scholar, and ClinicalTrials.gov, ultimately including 13 preclinical studies, 14 clinical studies, and 4 published interventional trials, while noting 19 additional trials in progress or completed but unpublished. The review describes convergent signals from both animal models and human studies suggesting that GLP-1RAs may reduce alcohol consumption and improve alcohol-related outcomes. Mechanistic preclinical work is highlighted to contextualize how these agents might modulate reward-related pathways. Clinical evidence includes observational studies drawing on real-world and electronic health record data, as well as a small number of randomized controlled trials. The authors acknowledge that the existing RCT evidence base remains limited and that further trials are needed to firmly establish efficacy. Mechanistic studies are also called for to more fully explain how GLP-1RAs may reduce alcohol intake. Case reports, commentaries, and preprints were excluded. This review does not itself generate new primary data.
Why this grade: This is a narrative review synthesizing preclinical and early-phase clinical data; it does not constitute an independent primary study or meta-analysis, so evidence grading reflects the review classification rather than direct experimental findings.
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.
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