Porcellati Francesca, Rossetti Paolo, Busciantella Natalia Ricci, Marzotti Stefania, Lucidi Paola, Luzio Steven, Owens David R, Bolli Geremia B, Fanelli Carmine G
Department of Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.
Diabetes Care. 2007 Oct;30(10):2447-52. doi: 10.2337/dc07-0002. Epub 2007 Jul 10.
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).
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).
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).
Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.
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）。
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）。
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）。
地特胰岛素在给药后的最初12小时内效果与甘精胰岛素相似，但在12 - 24小时内效果较低。
