Mader Julia K, Jensen Lene, Ingwersen Steen H, Christiansen Erik, Heller Simon, Pieber Thomas R
Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Division of Medicine and Science, Novo Nordisk A/S, Søborg, Denmark.
Clin Pharmacokinet. 2016 Nov;55(11):1457-1463. doi: 10.1007/s40262-016-0413-4.
The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D.
Subjects (18-64 years; body mass index 20.0-28.0 kg/m; glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D.
The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D.
Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665.
利拉鲁肽是一种已被批准用于治疗2型糖尿病（T2D）的胰高血糖素样肽-1受体激动剂，其药代动力学特性已在健康个体和T2D患者中得到确立。利拉鲁肽作为1型糖尿病（T1D）胰岛素治疗的辅助药物正在接受研究。这项单中心、双盲、安慰剂对照、交叉临床药理学试验首次分析了利拉鲁肽作为T1D胰岛素治疗附加药物的药代动力学特性。
受试者（年龄18 - 64岁；体重指数20.0 - 28.0 kg/m²；糖化血红蛋白≤9.5%）按1:1:1随机分为接受0.6、1.2或1.8 mg利拉鲁肽/安慰剂组。每组接受两个为期四周的治疗期（先使用利拉鲁肽然后使用安慰剂，或先使用安慰剂然后使用利拉鲁肽），中间间隔2至3周的洗脱期。两种试验药物均皮下注射，每日一次，作为胰岛素治疗的辅助药物。在每个治疗期结束时进行逐步低血糖钳夹试验（先前已报告数据）。药代动力学终点来自最后一剂后利拉鲁肽浓度 - 时间曲线，并将暴露情况与先前在健康志愿者和T2D患者中的试验数据进行比较。
利拉鲁肽在T1D中的药代动力学特性与在健康志愿者和T2D患者中观察到的特性相当。稳态浓度 - 时间曲线下面积（AUC）和最大血浆浓度数据与利拉鲁肽的剂量成正比。剂量标准化的利拉鲁肽AUC比较表明，在T1D中与胰岛素联合使用时的暴露情况与在T2D中观察到的相当。
在T1D患者中作为胰岛素辅助药物使用时，利拉鲁肽的药代动力学与T2D患者相当。ClinicalTrials.gov标识符：NCT01536665。
