Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Clin Pharmacokinet. 2021 Nov;60(11):1423-1434. doi: 10.1007/s40262-021-01030-0. Epub 2021 May 27.
Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This pooled analysis compared the pharmacokinetics and glucodynamics between URLi and Humalog in healthy subjects and patients with type 1 or type 2 diabetes mellitus.
The analysis included four randomized, double-blind, crossover, single-dose studies (healthy subjects [n = 74], patients with type 1 diabetes [n = 78], and type 2 diabetes [n = 38]) evaluating subcutaneous doses of 7, 15, or 30 U of URLi and Humalog during an 8- to 10-h euglycemic clamp procedure.
The pooled analysis showed an ~ 5-min faster onset of appearance, an ~8-fold greater exposure in the first 15 min, a 43% reduction in exposure beyond 3 h, and a 68-min shorter exposure duration with URLi vs Humalog across all study populations and dose range. Compared with Humalog, URLi had a 10-min faster onset of action, a 3-fold greater insulin action in the first 30 min, a 35% reduction in insulin action beyond 4 h, and a 44-min shorter duration of action across all populations and dose range. Overall exposure and insulin action were similar between URLi and Humalog for each dose level and study population.
Across the studied populations and dose range, URLi consistently demonstrated a faster absorption, reduced late exposure, and overall shorter exposure duration compared with Humalog. Similarly, URLi demonstrated earlier insulin action while reducing late insulin action and shorter insulin action compared with Humalog across the study populations and dose range.
NCT02942654 (registered: 21 October, 2016), NCT03286751 (registered: 15 September, 2017), NCT03166124 (registered: 23 May, 2017), and NCT03305822 (registered: 5 October, 2017).
超快速赖脯胰岛素（URLi）是一种新型赖脯胰岛素制剂，旨在更接近生理胰岛素分泌并改善餐后血糖控制。这项汇总分析比较了 URLi 和赖脯胰岛素在健康受试者和 1 型或 2 型糖尿病患者中的药代动力学和血糖动力学。
该分析包括四项随机、双盲、交叉、单次剂量研究（健康受试者 [n = 74]、1 型糖尿病患者 [n = 78] 和 2 型糖尿病患者 [n = 38]），评估了 7、15 或 30 U URLi 和赖脯胰岛素在 8 至 10 小时的正常血糖钳夹过程中的皮下剂量。
汇总分析显示，与赖脯胰岛素相比，所有研究人群和剂量范围内，URLi 的起效时间快约 5 分钟，在前 15 分钟的暴露量增加约 8 倍，3 小时后暴露量减少 43%，暴露时间缩短 68 分钟。与赖脯胰岛素相比，URLi 的作用开始时间快 10 分钟，在前 30 分钟的胰岛素作用增加 3 倍，4 小时后胰岛素作用减少 35%，在所有人群和剂量范围内的作用持续时间缩短 44 分钟。在每个剂量水平和研究人群中，URLi 和赖脯胰岛素的总体暴露量和胰岛素作用相似。
在研究人群和剂量范围内，与赖脯胰岛素相比，URLi 始终表现出更快的吸收、减少后期暴露和总体较短的暴露持续时间。同样，与赖脯胰岛素相比，URLi 在研究人群和剂量范围内表现出更早的胰岛素作用，同时减少晚期胰岛素作用并缩短胰岛素作用。
NCT02942654（注册日期：2016 年 10 月 21 日），NCT03286751（注册日期：2017 年 9 月 15 日），NCT03166124（注册日期：2017 年 5 月 23 日），NCT03305822（注册日期：2017 年 10 月 5 日）。
