背景:胰高血糖素样肽-1(GLP-1)受体激动剂减少啮齿动物和非人灵长类动物的酒精消耗。塞马鲁肽是一种新型的长效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,它还可以减少啮齿动物的酒精摄入量。
目的:本研究调查了司马鲁肽对酒精偏好的非洲绿猴酒精摄入的可能抑制作用。
方法:我们对表现出对酒精偏好的雄性猴子进行了媒介物对照研究。在被选中自愿饮酒的猴子中,在基线时测量酒精消耗量10天(周一至周五,为期两周).在此期间,猴子每天4小时获得酒精,每天24小时自由获得水。基线测量两周后,猴子被随机分配给司马鲁肽或媒介物。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,这些猴子接受递增剂量的司马鲁肽(最高0.05mg/kg)或媒介物皮下治疗,每周2次,共2周,在此期间无法获得酒精.向上滴定后,猴子每天4小时接触酒精,持续20天(周一至周五,持续4周),并对饮酒量进行了测量。在这个酒精暴露期,使用司马鲁肽(每周两次0.05mg/kg)或媒介物的治疗持续三周,然后进行一周的洗脱期。
结果:与车辆相比,司马鲁肽显著减少酒精摄入量。没有呕吐事件或饮水量变化的迹象。
结论:这些数据首次证明了司马鲁肽在减少非人类灵长类动物自愿饮酒方面的有效作用,并进一步证实了对司马鲁肽在酒精使用障碍患者中的作用进行临床试验的必要性。
BACKGROUND: 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.
OBJECTIVE: This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys.
METHODS: 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.
RESULTS: Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake.
CONCLUSIONS: 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.