Dirnena-Fusini Ilze, Riaz Misbah, Christiansen Sverre Christian, Carlsen Sven Magnus
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Endocrinology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Curr Ther Res Clin Exp. 2025 Jun 24;103:100803. doi: 10.1016/j.curtheres.2025.100803. eCollection 2025.
Glucagon leads to substantial but short-lived subcutaneous vasodilation. Using micro-amounts of glucagon at the insulin injection site increases insulin absorption.
We hypothesized that a premixed solution of insulin and nanogram doses of glucagon would improve the pharmacokinetic and pharmacodynamic properties of subcutaneously injected insulin.
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.
When premixed insulin Lyumjev/glucagon was injected, insulin T decreased from 33 to 20 minutes (SE = 6.6, = 0.08), and C was 2-fold higher than that in the control group (100 mU/L vs 46 mU/L, SE = 4.8, = 0.007). When premixed insulin Humalog/glucagon was injected, T and C did not change significantly ( = 0.53 and = 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, = 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 ( = 0.102) compared with the control groups.
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.
胰高血糖素可导致显著但短暂的皮下血管舒张。在胰岛素注射部位使用微量胰高血糖素可增加胰岛素吸收。
我们假设胰岛素与纳克剂量胰高血糖素的预混溶液会改善皮下注射胰岛素的药代动力学和药效学特性。
在这一系列概念验证实验中，纳入了17头麻醉猪。9头猪纳入对照组；它们接受皮下注射10单位赖脯胰岛素（Lyumjev或优泌乐）。8头猪纳入胰高血糖素组；它们接受10单位预混胰岛素（Lyumjev或优泌乐）/胰高血糖素溶液（每单位胰岛素含5纳克胰高血糖素）。频繁采集动脉血210分钟以评估胰岛素和葡萄糖浓度。通过正常血糖钳夹研究评估对葡萄糖代谢的影响。
注射预混胰岛素Lyumjev/胰高血糖素时，胰岛素T从33分钟降至20分钟（标准误 = 6.6，P = 0.08），C比对照组高2倍（100 mU/L对46 mU/L，标准误 = 4.8，P = 0.007）。注射预混胰岛素优泌乐/胰高血糖素时，T和C无显著变化（分别为P = 0.53和P = 0.83）。注射胰岛素Lyumjev/胰高血糖素时，前15分钟胰岛素AUC增加两倍（946 mU×min/L对337 mU×min/L，标准误 = 196，P = 0.02）。注射优泌乐/胰高血糖素时观察到类似趋势（306 mU×min/L对65 mU×min/L，标准误 = 125），尽管与对照组相比该差异未达到统计学显著性（P = 0.102）。
这一系列在麻醉猪身上进行的概念验证实验表明，在速效赖脯胰岛素制剂中预混纳克剂量的胰高血糖素可能会加快皮下注射胰岛素的吸收。
