走进利拉鲁肽 更多 >>
继日本中央社会保险医疗委员会批准了Victoza®（利拉鲁肽）的定价之后，诺和诺德制药公司计划将尽快在当地市场推出这种产品。诺和诺德表示，Victoza®是首个在日本获准上市的GLP-1类药物，既可以单独用药，也可以作为辅助药物与磺脲类降糖药(SU)联用。
Pharmacology of GLP-1-based therapies
Glucagon-like peptide-1 GLP-1 is a naturally occurring 30-amino acid eptide synthesised in intestinal endocrine L cells. GLP-1 mediates glucose homeostasis through stimulation of glucose-dependent insulin secretion, biosynthesis of insulin and inhibition of glucagon secretion. These effects have potential clinical value in type 2 diabetes.
However, because native GLP-1 is rapidly degraded to its inactive form by dipeptidyl peptidase-4 (DPP-4), it has a short half-life in vivo. Strategies to overcome this therapeutic limitation include developing GLP-1 mimetics and analogues with longer half-lives and to inhibit DPP-4. Exenatide (exendin-4) is a 39-amino acid peptide originally derived from the venom of the Gila monster lizard, and shares a 53% sequence identity with human GLP-1. Exenatide has a longer circulating half-life, reflecting relative resistance to DPP-4 degradation, and is administered twice daily.
Liraglutide is a once-daily human GLP-1 analogue with high (97%) sequence identity. The specific structural modifications that characterise liraglutide result in increased self-association (allowing slow absorption from the subcutaneous depot), promote albumin binding and reduce susceptibility to DPP-4, giving liraglutide a halflife of 13 hours after once-daily administration. Preliminary studies of exenatide and liraglutide showclinically relevant reductions in glycosylated haemoglobin A1c (HbA1c) compared with placebo,without hypoglycaemia andwithweight loss of up to 3 kg.
DPP-4 inhibitors, such as vildagliptin (not available in the USA) and sitagliptin can help stabilise postprandial GLP-1 levels and thus produce desirable effects on insulin and glucagon production. The potential forweight reductionwith DPP-4 inhibitors appears limited, perhaps reflecting the limited increase in GLP-1 levels achieved with these agents.
编辑: helen
以下网友留言只代表网友个人观点，不代表网站观点
