Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Clin Drug Investig. 2013 Jul;33(7):515-21. doi: 10.1007/s40261-013-0096-7.
Insulin degludec (IDeg) is a new-generation basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which IDeg monomers are slowly and continuously absorbed to provide an ultra-long action profile. This double-blind, crossover, randomized study compared the pharmacokinetic and pharmacodynamic properties between IDeg 100 U/mL (U100) and IDeg 200 U/mL (U200) under steady-state (SS) conditions in subjects with type 1 diabetes mellitus.
Participants (n = 33 adults) underwent 8-day treatment periods with 0.4 U/kg IDeg U100 and IDeg U200 given once daily with insulin aspart at mealtimes. On day 8, a 26-h euglycaemic glucose clamp (5.5 mmol/L) was performed.
The concentration-time profiles of IDeg U100 and IDeg U200 were similar, and a post-hoc analysis showed bioequivalence between these formulations, as the 90 % confidence intervals (CIs) of the U200/U100 ratios for area under the steady-state serum IDeg concentration-time curve during a dosing interval (τ; 0-24 h) (AUCτ,SS,IDeg) (0.99 [0.91-1.07]) and maximum steady-state IDeg concentration during a dosing interval (τ) (C max,SS,IDeg) (0.93 [0.84-1.02]) were within the interval 0.80-1.25. Comparable glucose infusion rates (GIR) were observed for IDeg U100 and IDeg U200 (AUCτ,SS,GIR [mg/kg]: 2,255 vs. 2,123) and the mean ratio (95 % CI) of IDeg U200/U100 for the primary endpoint (AUCτ,SS,GIR) was 0.94 [0.86-1.03]. For both formulations, the glucose-lowering effect of IDeg was evenly distributed between the first and second 12 h post-dosing (U100: AUC12,SS,GIR/AUC24,SS,GIR = 48 %; U200: AUC12,SS,GIR/AUC24,SS,GIR = 46 %). Both formulations were well tolerated, and no safety events of significance were identified.
IDeg U100 and U200 formulations are bioequivalent and have similar pharmacodynamic profiles at SS, implying that they can be used interchangeably in clinical practice.
胰岛素德谷胰岛素（IDeg）是一种新型基础胰岛素，皮下注射后形成可溶性多六聚体，从而形成一个储库，其中 IDeg 单体缓慢且持续吸收，提供超长作用谱。这项双盲、交叉、随机研究比较了在稳态条件下，1 型糖尿病患者中德谷胰岛素 100U/mL（U100）和 200U/mL（U200）的药代动力学和药效学特性。
参与者（n=33 名成年人）接受为期 8 天的治疗期，每天一次给予 0.4U/kg IDeg U100 和 IDeg U200，同时给予门冬胰岛素进餐时。在第 8 天，进行 26 小时的血糖钳夹（5.5mmol/L）。
IDeg U100 和 IDeg U200 的浓度-时间曲线相似，事后分析显示这两种制剂具有生物等效性，因为在 0.80-1.25 区间内，U200/U100 比值的 90%置信区间（CI）在稳态血清 IDeg 浓度-时间曲线下面积（AUCτ，SS，IDeg）（0.99[0.91-1.07]）和最大稳态 IDeg 浓度在一个给药间隔（τ）（C max，SS，IDeg）（0.93[0.84-1.02]）。对于 IDeg U100 和 IDeg U200 观察到相似的葡萄糖输注率（GIR）（AUCτ，SS，GIR[mg/kg]：2255 与 2123），并且主要终点（AUCτ，SS，GIR）的 IDeg U200/U100 均值比值（95%CI）为 0.94[0.86-1.03]。对于这两种制剂，IDeg 的降血糖作用在给药后第一和第二 12 小时均匀分布（U100：AUC12，SS，GIR/AUC24，SS，GIR=48%；U200：AUC12，SS，GIR/AUC24，SS，GIR=46%）。两种制剂均耐受良好，未发现有意义的安全性事件。
IDeg U100 和 U200 制剂具有生物等效性，在稳态时具有相似的药效学特征，这意味着它们可以在临床实践中互换使用。
