1型糖尿病患者稳态下长效胰岛素类似物甘精胰岛素和地特胰岛素的药代动力学与药效学比较：一项双盲、随机、交叉研究。

Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes: a double-blind, randomized, crossover study.

作者信息

Porcellati Francesca, Rossetti Paolo, Busciantella Natalia Ricci, Marzotti Stefania, Lucidi Paola, Luzio Steven, Owens David R, Bolli Geremia B, Fanelli Carmine G

机构信息

Department of Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.

出版信息

Diabetes Care. 2007 Oct;30(10):2447-52. doi: 10.2337/dc07-0002. Epub 2007 Jul 10.

DOI:10.2337/dc07-0002

PMID:17623819

Abstract

OBJECTIVE

To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 +/- 10 years, BMI 22.4 +/- 1.6 kg/m2, and A1C 7.2 +/- 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).

RESEARCH DESIGN AND METHODS

Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was >150 mg/dl).

RESULTS

With glargine, plasma glucose remained at 103 +/- 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose <180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P < 0.001). Estimated total insulin activity (GIR area under the curve [AUC](0-end of GIR)) was 1,412 +/- 662 and 915 +/- 225 mg/kg (glargine vs. detemir, P < 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids(0-24 h) 11 +/- 1.7 vs. 8 +/- 2.8 mmol/l, respectively, P < 0.001).

CONCLUSIONS

Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.

摘要

目的

比较甘精胰岛素和地特胰岛素的药代动力学和药效学，对24例1型糖尿病患者（年龄38±10岁，体重指数22.4±1.6kg/m²，糖化血红蛋白7.2±0.7%）进行研究，患者接受为期2周的甘精胰岛素或地特胰岛素每日一次治疗（随机、双盲、交叉研究）。

研究设计与方法

皮下注射0.35单位/千克后，将血糖钳定在100mg/dl达24小时。主要终点为作用结束（血糖>150mg/dl的时间）。

结果

使用甘精胰岛素时，血糖在24小时内维持在103±3.6mg/dl，所有受试者均完成研究。使用地特胰岛素时，16小时后血糖逐渐升高，只有8例受试者（33%）在血糖<180mg/dl的情况下完成研究。地特胰岛素和甘精胰岛素的葡萄糖输注率（GIR）在12小时内相似，之后地特胰岛素下降更快（P<0.001）。估计的总胰岛素活性（GIR曲线下面积[AUC](0 - GIR结束)）分别为1412±662和915±225mg/kg（甘精胰岛素与地特胰岛素相比，P<0.05），作用结束的中位时间分别为24小时和17.5小时（甘精胰岛素与地特胰岛素相比，P<0.001）。地特胰岛素的抗脂解作用低于甘精胰岛素（游离脂肪酸的AUC(0 - 24小时)分别为11±1.7和8±2.8mmol/l，P<0.001）。