Fink-Jensen Anders, Wörtwein Gitta, Klausen Mette Kruse, Holst Jens Juul, Hartmann Bolette, Thomsen Morgan, Ptito Maurice, Beierschmitt Amy, Palmour Roberta M
Laboratory of Neuropsychiatry, Mental Health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Hovedvejen 17, Frederiksberg, DK-2000, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Psychopharmacology (Berl). 2025 Jan;242(1):63-70. doi: 10.1007/s00213-024-06637-2. Epub 2024 Jun 17.
Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents.
This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys.
We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period.
Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake.
These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder.
胰高血糖素样肽-1（GLP-1）受体激动剂可减少啮齿动物和非人类灵长类动物的酒精摄入量。司美格鲁肽是一种新型长效GLP-1受体激动剂，在临床上广泛用于治疗2型糖尿病和肥胖症。据报道，它还能减少啮齿动物的酒精摄入量。
本研究调查司美格鲁肽对偏爱酒精的非洲绿猴酒精摄入量的可能抑制作用。
我们对表现出对酒精有偏好的雄性猴子进行了一项对照研究。在选择自愿饮酒的猴子中，在基线期（两周内周一至周五）测量十天的酒精摄入量。在此期间，猴子每天有4小时可获取酒精，每天24小时可自由饮水。在进行两周的基线测量后，将猴子随机分为司美格鲁肽组或对照组。每组由十只猴子组成，两组在基线酒精摄入量方面保持平衡。在基线期之后，猴子每周皮下注射两次递增剂量的司美格鲁肽（最高达0.05 mg/kg）或对照剂，持续两周，在此期间不提供酒精。滴定后，猴子每天有4小时可获取酒精，持续20天（四周内周一至周五），并测量酒精摄入量。在这个酒精暴露期，继续用司美格鲁肽（0.05 mg/kg，每周两次）或对照剂治疗三周，随后有一周的洗脱期。
与对照组相比，司美格鲁肽显著降低了酒精摄入量。没有催吐事件的迹象或饮水量的变化。
这些数据首次证明了司美格鲁肽在减少非人类灵长类动物自愿酒精摄入量方面的显著效果，并进一步证实了开展临床试验以研究司美格鲁肽对酒精使用障碍患者影响的必要性。
