Nano-Amounts of Glucagon Premixed With Fast-Acting Insulin Lispro: Effect on Insulin Absorption in Pigs

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental Pub Date : 2025-01-01 DOI:10.1016/j.curtheres.2025.100803

Ilze Dirnena-Fusini PhD , Misbah Riaz MSc , Sverre Christian Christiansen MD, PhD , Sven Magnus Carlsen MD, PhD

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引用次数: 0

Abstract

Background

Glucagon leads to substantial but short-lived subcutaneous vasodilation. Using micro-amounts of glucagon at the insulin injection site increases insulin absorption.

Objective

We hypothesized that a premixed solution of insulin and nanogram doses of glucagon would improve the pharmacokinetic and pharmacodynamic properties of subcutaneously injected insulin.

Methods

In this series of proof-of-concept experiments, 17 anesthetized pigs were included. Nine pigs were included in the control groups; they received a subcutaneous injection of 10 U of insulin lispro (Lyumjev^Ⓡ or Humalog^Ⓡ). Eight pigs were included in the glucagon groups; they received 10 U of a premixed insulin (Lyumjev^Ⓡ or Humalog^Ⓡ)/glucagon solution (5 ng glucagon/unit of insulin). Arterial blood was frequently sampled for 210 minutes to assess insulin and glucose concentrations. The impact on glucose metabolism was evaluated through euglycemic clamp investigation.

Results

When premixed insulin Lyumjev^Ⓡ/glucagon was injected, insulin T_max decreased from 33 to 20 minutes (SE = 6.6, P = 0.08), and C_max was 2-fold higher than that in the control group (100 mU/L vs 46 mU/L, SE = 4.8, P = 0.007). When premixed insulin Humalog^Ⓡ/glucagon was injected, T_max and C_max did not change significantly (P = 0.53 and P = 0.83, respectively). Insulin AUC for the first 15 minutes increased two-fold when insulin Lyumjev^Ⓡ/glucagon was injected (946 mU×min/L vs 337 mU×min/L, SE = 196, P = 0.02). A similar trend was observed when Humalog^Ⓡ/glucagon was injected (306 mU×min/L vs 65 mU×min/L, SE = 125), although this difference did not reach statistical significance (P = 0.102) compared with the control groups.

Conclusions

This series of proof-of-concept experiments in anesthetized pigs indicate that premixing nanogram doses of glucagon in fast-acting insulin lispro formulations may speed up the absorption of subcutaneously injected insulin.

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纳米级胰高血糖素与速效胰岛素利斯普罗预混：对猪胰岛素吸收的影响

背景：胰高血糖素导致大量但短暂的皮下血管扩张。在胰岛素注射部位使用微量胰高血糖素可以增加胰岛素的吸收。目的假设胰岛素与毫微克胰高血糖素的预混溶液可以改善皮下注射胰岛素的药动学和药效学特性。方法在这一系列的概念验证实验中，选取17头麻醉猪。9头猪作为对照组；皮下注射10u胰岛素lispro （LyumjevⓇ或HumalogⓇ）。8头猪分为胰高血糖素组；他们接受10单位胰岛素（LyumjevⓇ或HumalogⓇ）/胰高血糖素溶液（5 ng胰高血糖素/单位胰岛素）的预混合。经常抽取动脉血210分钟，以评估胰岛素和葡萄糖浓度。通过正糖钳法观察对糖代谢的影响。结果注射Lyumjev胰岛素Ⓡ/胰高血糖素预混剂后，胰岛素Tmax从33 min降低至20 min (SE = 6.6, P = 0.08)， Cmax比对照组提高2倍（100 mU/L vs 46 mU/L, SE = 4.8, P = 0.007）。注射预混合胰岛素HumalogⓇ/胰高血糖素时，Tmax和Cmax无显著变化（P = 0.53和P = 0.83）。Lyumjev胰岛素Ⓡ/胰高血糖素组前15分钟胰岛素AUC升高2倍（946 mU×min/L vs 337 mU×min/L, SE = 196, P = 0.02）。注射HumalogⓇ/胰高血糖素组也有类似的趋势（306 mU×min/L vs 65 mU×min/L, SE = 125），但与对照组相比差异无统计学意义（P = 0.102）。结论在麻醉猪身上进行的一系列概念验证实验表明，在速效胰岛素制剂中预混纳克剂量的胰高血糖素可以加速皮下注射胰岛素的吸收。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Therapeutic Research-clinical and Experimental 医学-药学

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

3 months

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