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新型基础胰岛素的研发:在 2 型糖尿病患者中应用这类胰岛素是否具有临床优势?

The development of new basal insulins: is there any clinical advantage with their use in type 2 diabetes?

机构信息

Second University of Naples, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging , Naples , Italy.

出版信息

Expert Opin Biol Ther. 2014 Jun;14(6):799-808. doi: 10.1517/14712598.2014.895812. Epub 2014 Mar 27.

Abstract

INTRODUCTION

The basal insulin products currently on market do not optimally mimic endogenous insulin secretion. These unmet clinical needs have fueled the development of new basal insulin analogues for improving their pharmacokinetics/pharmacodynamics profile.

AREAS COVERED

We review the recent literature investigating the efficacy and safety of new basal insulin analogues in type 2 diabetes, as in the USA, insulin utilization accounted for 26% of treatment visits for these patients in 2012. Insulin degludec is a desB30 insulin acylated at the LysB29 residue with a glutamate linker and 16-carbon fatty diacyl side chain. Insulin lispro has been PEGylated at lysine B28, via a urethane bond, which increases the hydrodynamic size of the molecule and reduces its absorption and clearance following subcutaneous administration. Glargine U300 represents a new high-strength glargine formulation (300 U/ml): once injected, U300 forms a compact subcutaneous depot with a smaller surface area to produce a more gradual and prolonged release. Both PEG-lispro and glargine U300 are not yet on the market.

EXPERT OPINION

Ultra-long acting and high-strength formulations of new basal analogues have the potential for less glycemic variability, less (nocturnal) hypoglycemia and weight-loss advantage for PEG-lispro. However, these new basal insulin analogues need to be monitored closely for adverse signals.

摘要

简介

目前市场上的基础胰岛素产品并不能最佳地模拟内源性胰岛素分泌。这些未满足的临床需求推动了新型基础胰岛素类似物的开发,以改善其药代动力学/药效学特征。

涵盖领域

我们回顾了最近关于新型基础胰岛素类似物在 2 型糖尿病中的疗效和安全性的文献,因为在美国,2012 年胰岛素的使用占这些患者治疗就诊的 26%。胰岛素德谷胰岛素是一种在赖氨酸 B29 位置酰化的 DesB30 胰岛素,带有谷氨酸连接子和 16 碳脂肪酸二酰侧链。胰岛素赖脯肽已通过氨酯键在赖氨酸 B28 位聚乙二醇化,这增加了分子的流体力学尺寸,从而减少了皮下给药后的吸收和清除。甘精胰岛素 U300 是一种新的高强度甘精胰岛素制剂(300U/ml):一旦注射,U300 会在皮下形成一个紧凑的储存库,表面积较小,从而产生更缓慢和更持久的释放。PEG-赖脯肽和甘精胰岛素 U300 都尚未上市。

专家意见

新型基础类似物的超长效和高强度制剂可能具有更低的血糖变异性、更少的(夜间)低血糖和 PEG-赖脯肽的体重减轻优势。然而,这些新型基础胰岛素类似物需要密切监测不良反应信号。

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