Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes
Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes
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DOI：
10.1111/j.1463-1326.2012.01638.x
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发表时间：
2012-10-01
影响因子：
5.8
通讯作者：
Haahr, H.
中科院分区：
文献类型：
--
作者：
Heise, T.;Nosek, L.;Haahr, H.
目的：胰岛素去gludec （Insulin degludec, IDeg）是一种新一代的超长效基础胰岛素，皮下注射后形成可溶性多六聚体，形成一个储库，IDeg从储库被缓慢而持续地吸收进入循环。这项双盲、两期、不完全阻断交叉试验研究了IDeg在2型糖尿病患者稳态（SS）下的药效学和药代动力学特性。方法：49例胰岛素组患者不同时服用口服降糖药，每日1次给予IDeg(0.4、0.6和/或0.8 U/kg)，连续2个6 d，间隔13 ~ 21 d。在第6天给药后，受试者进行26小时的血糖钳夹(bio定子(R)；钳形血糖：90 mg/dl；5.0更易/ l)。末次给药后120 h取药代动力学样本。结果：在所有剂量水平下，平均葡萄糖输注速率（GIR）曲线是平坦和稳定的。IDeg的降糖作用在给药间隔tau内均匀分布，4个6小时间隔的曲线下面积（AUC）约为总AUC的25% （AUC(GIR,tau，SS)）。总降糖效果随剂量增加呈线性增加。所有受试者的血糖水平都非常接近钳夹目标，直到钳夹结束。IDeg的末端半衰期在稳态下约为25 h。IDeg耐受性良好，无安全隐患。未见注射部位反应报告。结论：IDeg对2型糖尿病患者有稳定的降糖作用。
Aims: Insulin degludec (IDeg) is a new-generation, ultra-long-acting basal insulin that forms soluble multihexamers upon subcutaneous injection, resulting in a depot from which IDeg is absorbed slowly and continuously into circulation. This double-blind, two-period, incomplete block cross-over trial investigated the pharmacodynamic and pharmacokinetic properties of IDeg at steady state (SS) in people with type 2 diabetes.Methods: Forty-nine subjects treated with insulin without concomitant oral anti-diabetic drugs were given IDeg (0.4, 0.6 and/or 0.8 U/kg) once daily for two 6-day periods, separated by an interval of 13-21 days. Following dosing on Day 6, subjects underwent a 26-h euglycaemic glucose clamp (Biostator (R); clamp blood glucose level: 90 mg/dl; 5.0 mmol/l). Pharmacokinetic samples were taken until 120 h after last dosing.Results: For all dose levels, the mean glucose infusion rate (GIR) profiles were flat and stable. The glucose-lowering effect of IDeg was evenly distributed over the dosing interval tau, with area under the curve (AUC) for each of the four 6-h intervals being approximately 25% of the total AUC (AUC(GIR,tau,SS)). Total glucose-lowering effect increased linearly with increasing dose. The blood glucose levels of all subjects stayed very close to the clamp target until end of clamp. The terminal half-life of IDeg was approximately 25 h at steady state. IDeg was well tolerated and no safety concerns were identified. No injection site reactions were reported.Conclusions: IDeg has a flat and consistent glucose-lowering effect in people with type 2 diabetes.