Background

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 pharmacokinetics, glucodynamics, safety, and tolerability of URLi and Humalog^® in patients with type 1 diabetes mellitus (T1DM).

Methods

This was a phase I, two-period, randomised, double-blind, crossover glucose clamp study in younger adult (aged 18–45 years; n = 41) and elderly (aged ≥65 years; n = 39) patients with T1DM. At each dosing visit, patients received either URLi or Humalog (15 units subcutaneously) followed by a 10 h automated euglycaemic clamp procedure. Serum insulin lispro and blood glucose were measured.

Results

Insulin lispro appeared in serum 6 min faster, and exposure was 7.2-fold greater over the first 15 min postdose with URLi versus Humalog in both age groups. Exposure beyond 3 h postdose was 39–41% lower, and exposure duration was reduced by 72–74 min with URLi versus Humalog in both age groups. Onset of insulin action was 11–12 min faster, and insulin action was 3-fold greater over the first 30 min postdose with URLi versus Humalog in both age groups. Insulin action beyond 4 h postdose was 44–54% lower, and duration of action was reduced by 34–44 min with URLi versus Humalog in both age groups. Overall exposure and total insulin action remained similar for both treatments. URLi and Humalog were well tolerated.

Conclusion

In patients with T1DM, URLi showed ultra-rapid pharmacokinetics and glucodynamics, with the differences between URLi and Humalog in elderly patients mirroring those in younger adults.

ClinicalTrials.gov identifier: NCT03166124.

中文翻译：

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超快速 Lispro (URLi) 与 Humalog® (Lispro) 在 1 型糖尿病年轻成人和老年患者中的药代动力学和葡萄糖动力学：一项随机对照试验。

背景

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 URLi 和 Humalog ^®在 1 型糖尿病 (T1DM) 患者中的药代动力学、糖动力学、安全性和耐受性。

方法

这是一项针对年轻成人（18-45 岁；n  = 41）和老年（≥65 岁；n  = 39）T1DM 患者的I 期、两期、随机、双盲、交叉葡萄糖钳夹研究。在每次给药访问中，患者接受 URLi 或 Humalog（皮下注射 15 个单位），然后进行 10 小时自动血糖正常钳夹程序。测量血清赖脯胰岛素和血糖。

结果

两个年龄组的 URLi 与 Humalog 相比，赖脯胰岛素出现在血清中的速度要快 6 分钟，并且在服用 URLi 后的前 15 分钟内暴露量增加了 7.2 倍。两个年龄组的 URLi 与 Humalog 相比，给药后 3 小时后的暴露量降低了 39-41%，暴露持续时间减少了 72-74 分钟。两个年龄组的 URLi 与 Humalog 相比，胰岛素作用起效快 11-12 分钟，胰岛素作用在给药后的前 30 分钟内高 3 倍。两个年龄组的 URLi 与 Humalog 相比，给药后 4 小时后的胰岛素作用降低了 44-54%，作用持续时间减少了 34-44 分钟。两种治疗的总暴露量和总胰岛素作用保持相似。URLi 和 Humalog 的耐受性良好。

结论

在 T1DM 患者中，URLi 显示出超快速的药代动力学和糖动力学，老年患者中 URLi 和 Humalog 之间的差异反映了年轻人的差异。

ClinicalTrials.gov 标识符：NCT03166124。