Eli Lilly and Company, Indianapolis, Indiana, USA.
Profil, Mainz, Germany.
Diabetes Obes Metab. 2022 Feb;24(2):196-203. doi: 10.1111/dom.14563. Epub 2021 Oct 24.
To compare the pharmacokinetics (PK), glucodynamics (GD), and tolerability following single and multiple daily subcutaneous (SC) doses of ultra rapid lispro (URLi) and Humalog® in patients with type 1 diabetes mellitus (T1D).
This was a two-part, randomized, double-blind, Phase 1b study. Part A used a six-period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 min before, immediately before, and 15 min after the start of the meal. Part B evaluated URLi or Humalog during 2 weeks of multiple daily dosing with a parallel design. The PK and GD were assessed following MMTTs at the beginning and end of the 2-week period when insulins were administered immediately before the start of the meal.
URLi increased the insulin exposure within the first 30 min postdose by 2.2-fold and reduced the time to early half-maximal drug concentration by 37% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal compared with Humalog. Comparing the same meal-to-dose timing between the insulins, postprandial glucose excursion over 5 hours was reduced by 40%-44% for all three dose timings (-15, 0, and +15 min) with URLi, achieving statistical significance for the 0- and +15-min timings. The PK and GD profiles were sustained after daily SC dosing for 2 weeks in patients with T1D. The number of documented hypoglycaemic events was similar between URLi and Humalog during the postprandial period of the MMTTs and the outpatient period.
URLi showed accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal-to-dose timings compared with Humalog and was well tolerated in patients with T1D.
比较 1 型糖尿病（T1D）患者单次和每日多次皮下（SC）给予超快速赖脯胰岛素（URLi）和赖脯胰岛素（Humalog®）后的药代动力学（PK）、血糖动力学（GD）和耐受性。
这是一项两部分、随机、双盲、1b 期研究。第 A 部分采用六周期交叉设计，评估单次给药后固体混合餐耐量试验（MMTT）的 PK 和 GD 反应，URLi 或 Humalog 给药时间分别为餐前 15 分钟、餐前即刻和餐后 15 分钟。第 B 部分评估 2 周内每日多次给药时 URLi 或 Humalog 的情况，采用平行设计。在 2 周期间开始和结束时进行 MMTT，当胰岛素在餐前即刻给药时评估 PK 和 GD。
与 Humalog 相比，URLi 在给药后 30 分钟内将胰岛素暴露量增加了 2.2 倍，将早期半最大药物浓度时间缩短了 37%。总体而言，与 Humalog 相比，URLi 在餐前、餐前即刻或餐后给药时，餐后血糖降低效果更好。在胰岛素相同的餐-剂量时间比较中，对于所有三个剂量时间（-15、0 和+15 分钟），URLi 使餐后 5 小时的血糖波动减少了 40%-44%，在 0-和+15 分钟时间点达到统计学意义。在 T1D 患者中，每日 SC 给药 2 周后，PK 和 GD 特征持续。在 MMTT 的餐后和门诊期间，URLi 和 Humalog 记录的低血糖事件数量相似。
与 Humalog 相比，URLi 显示出加速的赖脯胰岛素吸收和更大的餐后血糖降低，在不同的餐-剂量时间点均具有良好的耐受性。
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