Background and objective

Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the insulin lispro pharmacokinetics and glucodynamics, safety and tolerability of URLi and Humalog^® after a single subcutaneous dose in patients with type 2 diabetes mellitus (T2DM).

Methods

This was a phase I, randomised, two-period, two-treatment, double-blind, crossover study in 38 patients with T2DM. At each dosing visit, patients received either 15 units of URLi or Humalog, followed by a 10 h automated euglycaemic clamp procedure. Serum insulin lispro and blood glucose were measured.

Results

Insulin lispro appeared in the serum 5 min faster (p < 0.0001) and exposure was 6.4-fold greater in the first 15 min (p < 0.0001) with URLi versus Humalog. Exposure beyond 3 h postdose was 26% lower and the duration of exposure was 51 min shorter with URLi versus Humalog. Onset of insulin action was 13 min faster (p < 0.0001) and insulin action was 4.2-fold greater within the first 30 min (p < 0.0001) with URLi versus Humalog. Insulin action beyond 4 h postdose was 20% lower (p = 0.0099) with URLi versus Humalog. Overall insulin lispro exposure and total glucose infused were similar for URLi and Humalog. Both treatments were well tolerated.

Conclusions

This is the first study to investigate URLi in patients with T2DM using a euglycaemic clamp procedure. URLi demonstrated ultra-rapid pharmacokinetics and glucodynamics in patients with T2DM.

ClinicalTrials.gov identifier:

NCT03305822.

中文翻译：

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Ultra Rapid Lispro (URLi) 与 Humalog® (Lispro) 在 2 型糖尿病患者中的药代动力学和葡萄糖动力学：一项 I 期随机、交叉研究。

背景与目的

超快速赖脯胰岛素 (URLi) 是一种新型赖脯胰岛素制剂，旨在更紧密地匹配生理胰岛素分泌并改善餐后血糖控制。本研究比较了2 型糖尿病 (T2DM) 患者单次皮下注射后，URLi 和 Humalog ^{® 的}赖脯胰岛素药代动力学和糖动力学、安全性和耐受性。

方法

这是一项对 38 名 T2DM 患者进行的 I 期、随机、两期、两种治疗、双盲、交叉研究。在每次给药访问中，患者接受 15 个单位的 URLi 或 Humalog，然后是 10 小时的自动血糖正常钳夹程序。测量血清赖脯胰岛素和血糖。

结果

赖脯胰岛素在血清中的出现速度快 5 分钟 ( p  < 0.0001)，并且在前 15 分钟 ( p  < 0.0001) 中，使用 URLi 与 Humalog 的暴露量增加了 6.4 倍。URLi 与 Humalog 相比，给药后 3 小时后的暴露量降低了 26%，暴露持续时间缩短了 51 分钟。 URLi 与 Humalog 相比，胰岛素作用开始快 13 分钟（p  < 0.0001），并且在前 30 分钟内胰岛素作用增加 4.2 倍（p < 0.0001）。 URLi 与 Humalog 相比，给药后 4 小时后的胰岛素作用降低了 20% ( p = 0.0099)。URLi 和 Humalog 的总体赖脯胰岛素暴露量和总葡萄糖输注量相似。两种治疗均耐受良好。

结论

这是第一项使用正常血糖钳夹程序调查 T2DM 患者 URLi 的研究。URLi 在 T2DM 患者中展示了超快速的药代动力学和糖动力学。

ClinicalTrials.gov 标识符：

NCT03305822。