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Background <p>Alcohol use disorder (AUD) affects nearly half a billion people globally and is associated with significant physical and psychiatric comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for diabetes and obesity, have shown promise in modulating reward-related brain pathways, suggesting potential benefits in the management of AUD.</p> Methods <p>This systematic review and meta-analysis, registered in PROSPERO and conducted per PRISMA guidelines, assessed the effects of GLP-1RA use on AUD and alcohol-related outcomes in adults with obesity or type 2 diabetes mellitus. Five databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) were searched up to September 30, 2025. Random-effects models were applied, and sensitivity analyses examined result stability. No subgroup or meta-regression analyses were performed owing to the small number of eligible studies.</p> Results <p>Five observational cohort studies (three on AUD diagnosis, two on alcohol-related hospitalization) were included, with sample sizes ranging from 4,321 to &gt; 53,000 participants. GLP-1RA use was associated with a 28% lower risk of AUD diagnosis (HR = 0.72, 95% CI 0.59–0.89; I² = 65%). For alcohol-related hospitalization, a non-significant reduction was observed (HR = 0.76, 95% CI 0.57–1.01; I² = 77%). Leave-one-out sensitivity analyses confirmed the direction and magnitude of the AUD finding but highlighted the limited evidence base for hospitalization.</p> Conclusion <p>GLP-1RA use was associated with a reduced risk of AUD diagnosis, with a possible but non-significant reduction in alcohol-related hospitalization. Effects may be mediated through modulation of mesolimbic reward pathways and the gut–brain axis. Further large-scale trials are warranted to confirm these findings.</p> Graphical abstract <p></p>

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Repurposing GLP-1 receptor agonists for alcohol use disorder: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月8日

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  • Amir Nasrollahizadeh,
  • Ghazaleh Kheiri,
  • Sepide Javankiani,
  • Sadra Kheiri,
  • Seyedeh Fatemeh Hamzavi,
  • Mehdi Karimi,
  • Ehsan Amini-Salehi,
  • Mohammad Amin Karimi

摘要

Background

Alcohol use disorder (AUD) affects nearly half a billion people globally and is associated with significant physical and psychiatric comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for diabetes and obesity, have shown promise in modulating reward-related brain pathways, suggesting potential benefits in the management of AUD.

Methods

This systematic review and meta-analysis, registered in PROSPERO and conducted per PRISMA guidelines, assessed the effects of GLP-1RA use on AUD and alcohol-related outcomes in adults with obesity or type 2 diabetes mellitus. Five databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) were searched up to September 30, 2025. Random-effects models were applied, and sensitivity analyses examined result stability. No subgroup or meta-regression analyses were performed owing to the small number of eligible studies.

Results

Five observational cohort studies (three on AUD diagnosis, two on alcohol-related hospitalization) were included, with sample sizes ranging from 4,321 to > 53,000 participants. GLP-1RA use was associated with a 28% lower risk of AUD diagnosis (HR = 0.72, 95% CI 0.59–0.89; I² = 65%). For alcohol-related hospitalization, a non-significant reduction was observed (HR = 0.76, 95% CI 0.57–1.01; I² = 77%). Leave-one-out sensitivity analyses confirmed the direction and magnitude of the AUD finding but highlighted the limited evidence base for hospitalization.

Conclusion

GLP-1RA use was associated with a reduced risk of AUD diagnosis, with a possible but non-significant reduction in alcohol-related hospitalization. Effects may be mediated through modulation of mesolimbic reward pathways and the gut–brain axis. Further large-scale trials are warranted to confirm these findings.

Graphical abstract