Oesterle Tyler S, Ho Ming-Fen
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Brain Sci. 2025 Jun 29;15(7):702. doi: 10.3390/brainsci15070702.
BACKGROUND/OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs.
A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility.
Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders.
Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes.
背景/目的：胰高血糖素样肽-1受体激动剂（GLP-1RAs）最初是为通过增强胰岛素分泌和降低食欲来治疗2型糖尿病而研发的，现已成为酒精使用障碍（AUD）领域有前景的候选药物。这些药物具有双重作用机制，通过靶向外周代谢和中枢奖赏途径，与成瘾的多方面性质相契合。本综述聚焦于GLP-1RAs作为AUD新型治疗药物的当前临床试验及真实世界证据。我们还讨论了AUD临床试验的早期但令人鼓舞的结果、观察性及真实世界证据、安全性概况、精神科考量以及GLP-1RAs之外的未来研究方向。
按照PRISMA指南，在PubMed、Medline、谷歌学术、科学网及试验注册库中进行全面的英文文献检索。使用目标关键词，我们识别出关于GLP-1RAs用于酒精使用障碍的相关临床和观察性研究，排除不相关或非英文的研究，并评估所有研究的纳入资格。
在识别出的1080条记录中，有7项研究符合纳入标准。近期临床试验、大规模观察性研究及真实世界证据的结果表明，GLP-1RAs可能显著减少酒精摄入量、饮酒欲望及与酒精相关的住院次数。它们对奖赏处理的中枢作用，再加上总体良好的安全性概况，支持了其在代谢紊乱之外的潜在治疗作用。
新出现的证据表明GLP-1RAs是治疗AUD的一种有前景的新药物方法。正在进行的和未来的研究应优先开展更大规模、更长疗程的随机对照试验，纳入不同人群，尤其要关注治疗动机、共病的精神科状况及长期结局。
