Knudsen Lotte Bjerre
Global Drug Discovery, Novo Nordisk, Novo Nordisk Park, DK-2760 Maaloev, Denmark.
ACS Pharmacol Transl Sci. 2019 Aug 20;2(6):468-484. doi: 10.1021/acsptsci.9b00048. eCollection 2019 Dec 13.
Glucagon-like peptide-1 (GLP-1) has been in focus since the early 1980s as a long looked for incretin hormone, released from the gastrointestinal tract and with an important effect on glucose-dependent insulin secretion, providing efficient glucose lowering, with little risk for hypoglycemia. The enzyme dipeptidyl peptidase-4 (DPP-4) degrades GLP-1 very fast, and the remaining metabolite is cleared rapidly by the kidneys. Liraglutide is a fatty acid acylated analogue of GLP-1 that provides efficacy for 24 h/day. The mechanism of action for liraglutide is reviewed in detail with focus on pancreatic efficacy and safety, thyroid safety, and weight loss mechanism. Evolving science hypothesizes that GLP-1 has important effects on atherosclerosis, relevant for the cardiovascular benefit seen in the treatment of diabetes and obesity. Also, GLP-1 may be relevant in neurodegenerative diseases.
自20世纪80年代初以来,胰高血糖素样肽-1(GLP-1)一直备受关注,它是一种人们长期寻找的肠促胰岛素激素,由胃肠道释放,对葡萄糖依赖性胰岛素分泌有重要作用,能有效降低血糖,且低血糖风险小。二肽基肽酶-4(DPP-4)酶能非常快速地降解GLP-1,其剩余代谢产物会被肾脏迅速清除。利拉鲁肽是一种GLP-1脂肪酸酰化类似物,每天能提供24小时的疗效。本文详细综述了利拉鲁肽的作用机制,重点关注其对胰腺的疗效和安全性、甲状腺安全性以及减肥机制。不断发展的科学推测,GLP-1对动脉粥样硬化有重要影响,这与在糖尿病和肥胖症治疗中看到的心血管益处相关。此外,GLP-1可能与神经退行性疾病有关。