Scholtz H E, Pretorius S G, Wessels D H, Venter C, Potgieter M A, Becker R H A
Farmovs-Parexel Clinical Research Organisation, Bloemfontein, South Africa.
Acta Diabetol. 2003 Dec;40(4):156-62. doi: 10.1007/s00592-003-0105-z.
The absolute glucose disposal of insulin glargine (Lantus) was compared to that of regular human insulin in healthy subjects (n=20) using the euglycaemic clamp technique in a single-dose, double-blind, randomized, two-way crossover design. Subjects received 30-minute intravenous infusions of insulin glargine (0.1 IU/kg) or human insulin (0.1 IU/kg) and a 20% glucose solution infused at a variable rate to maintain euglycaemia at the subject's baseline glucose level. At equal baseline blood glucose levels (4.42 mmol/l [range, 4.00-5.16 mmol/l] and 4.42 mmol/l [range, 4.01-4.94 mmol/l], respectively), the area under the glucose infusion rate (GIR) time curves from 0-6 hours (AUC(0-6h)) was within the bioequivalence range (insulin glargine, 663.92 mg/kg; human insulin, 734.85 mg/kg). Both the time to maximum GIR and the suppression of serum C-peptide were similar with insulin glargine and human insulin. The resulting maximum serum insulin concentrations (Cmax) were 151.16 microIU/ml and 202.23 microIU/ml, and the time to Cmax (Tmax) was 30 minutes (the duration of the infusion). The observed differences in the Cmax (the mean value for insulin glargine was about 25% lower than that of human insulin) could be explained by lower cross-reactivity of insulin glargine in the human insulin radioimmunoassay. The employed intravenous route, though definitely not the intended clinical use of insulin glargine, provided the clinical evidence in healthy subjects that on a molar basis insulin glargine is equipotent to regular human insulin regarding glucose disposal.
在健康受试者（n = 20）中，采用单剂量、双盲、随机、双向交叉设计的正常血糖钳夹技术，比较了甘精胰岛素（来得时）与常规人胰岛素的绝对葡萄糖处置情况。受试者接受30分钟的静脉输注，分别输注甘精胰岛素（0.1 IU/kg）或人胰岛素（0.1 IU/kg），并以可变速率输注20%葡萄糖溶液，以将血糖维持在受试者的基线血糖水平。在相等的基线血糖水平（分别为4.42 mmol/l [范围，4.00 - 5.16 mmol/l]和4.42 mmol/l [范围，4.01 - 4.94 mmol/l]）下，0至6小时葡萄糖输注速率（GIR）时间曲线下的面积（AUC(0 - 6h)）在生物等效范围内（甘精胰岛素，663.92 mg/kg；人胰岛素，734.85 mg/kg）。甘精胰岛素和人胰岛素的达到最大GIR的时间以及血清C肽的抑制情况相似。产生的最大血清胰岛素浓度（Cmax）分别为151.16 μIU/ml和202.23 μIU/ml，达到Cmax的时间（Tmax）为30分钟（输注持续时间）。观察到的Cmax差异（甘精胰岛素的平均值比人胰岛素低约25%）可以通过甘精胰岛素在人胰岛素放射免疫测定中的交叉反应性较低来解释。所采用的静脉途径虽然肯定不是甘精胰岛素的预期临床使用途径，但在健康受试者中提供了临床证据，即在摩尔基础上，甘精胰岛素在葡萄糖处置方面与人胰岛素等效。
