Work

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

Year: 2025

Type: article

Abstract: Introduction Glucagon leads to a substantial but short-lived subcutaneous vasodilation. Using micro-amounts of glucagon at the insulin injection site increases the insulin absorption. We hypothesized that a pre-mixed solution of insulin and nanogram doses of glucagon would improve the pharmacokinetics and pharmacodynamics of subcutaneously injected insulin. Research design and methods In this series of proof-of-concept experiments, seventeen anaesthetized 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 two-fold higher compared to 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). Insulin Area Under the Curve 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 to the control groups. Conclusions This series of proof-of-concept experiment in anaesthetized pigs indicate that premixing nanogram doses of glucagon in fast-acting insulin lispro formulations may speed up the absorption of SC injected insulin.

Source: Current Therapeutic Research

DOI: 10.1016/j.curtheres.2025.100803

Authors: Ilze Dirnena-Fusini, Misbah Riaz, Sverre Christian Christiansen, Sven Magnus Carlsen

Institutions: Norwegian University of Science and Technology, St Olav's University Hospital

Language: English

Topic: Diabetes Management and Research

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690