Heise Tim, Hövelmann Ulrike, Zijlstra Eric, Stender-Petersen Kirstine, Jacobsen Jacob Bonde, Haahr Hanne
Profil Institut für Stoffwechselforschung GmbH, Hellersbergstraße 9, 41460, Neuss, Germany.
Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
Drugs Aging. 2017 Jan;34(1):29-38. doi: 10.1007/s40266-016-0418-6.
Due to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption. This study investigated the pharmacological properties of faster aspart in elderly subjects with type 1 diabetes mellitus (T1DM).
In a randomised, double-blind, two-period crossover trial, 30 elderly (≥65 years) and 37 younger adults (18-35 years) with T1DM received single subcutaneous faster aspart or IAsp dosing (0.2 U/kg) and underwent an euglycaemic clamp (target 5.5 mmol/L) for up to 12 h.
The pharmacokinetic and pharmacodynamic time profiles were left-shifted for faster aspart versus IAsp. In each age group, onset of appearance occurred approximately twice as fast (~3 min earlier) and early exposure (area under the concentration-time curve [AUC] for serum IAsp from time zero to 30 min [AUC]) was greater (by 86% in elderly and 67% in younger adults) for faster aspart than for IAsp. Likewise, onset of action occurred 10 min faster in the elderly and 9 min faster in younger adults, and early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 30 min [AUC]) was greater (by 109%) for faster aspart than for IAsp in both age groups. Total exposure (AUC) and the maximum concentration (C ) for faster aspart were greater (by 30 and 28%, respectively) in elderly than in younger adults. No age group differences were seen for the total (AUC) or maximum (GIR) glucose-lowering effect.
This study demonstrated that the ultra-fast pharmacological properties of faster aspart are similar in elderly subjects and younger adults with T1DM. ClinicalTrials.gov Identifier: NCT02003677.
由于人口老龄化，越来越多的老年糖尿病患者使用胰岛素。因此，研究这类人群中新型胰岛素的特性很重要。速效门冬胰岛素（更快起效的门冬胰岛素）是一种新剂型的门冬胰岛素（IAsp），其吸收更快。本研究调查了更快起效的门冬胰岛素在老年1型糖尿病（T1DM）患者中的药理学特性。
在一项随机、双盲、两阶段交叉试验中，30名老年（≥65岁）和37名年轻（18 - 35岁）的T1DM患者接受单次皮下注射更快起效的门冬胰岛素或IAsp（0.2 U/kg），并进行长达12小时的正常血糖钳夹试验（目标值5.5 mmol/L）。
与IAsp相比，更快起效的门冬胰岛素的药代动力学和药效学时间曲线左移。在每个年龄组中，更快起效的门冬胰岛素的起效时间约快两倍（早约3分钟），早期暴露（血清IAsp从0到30分钟的浓度 - 时间曲线下面积[AUC]）更大（老年组增加86%，年轻成人组增加67%）。同样，老年组起效时间快10分钟，年轻成人组快9分钟，两个年龄组中更快起效的门冬胰岛素的早期降糖效果（葡萄糖输注率[GIR]从0到30分钟的AUC）比IAsp更大（增加109%）。更快起效的门冬胰岛素的总暴露量（AUC）和最大浓度（C）在老年组比年轻成人组更高（分别高30%和28%）。在总（AUC）或最大（GIR）降糖效果方面未观察到年龄组差异。
本研究表明，更快起效的门冬胰岛素在老年和年轻T1DM患者中的超快速药理学特性相似。ClinicalTrials.gov标识符：NCT02003677。
