Comparative Pharmacokinetic/Pharmacodynamic Study of Liquid Stable Glucagon Versus Lyophilized Glucagon in Type 1 Diabetes Subjects

J Diabetes Sci Technol. 2016 Aug 22;10(5):1101-7. doi: 10.1177/1932296816653141. Print 2016 Sep.

Abstract

Background: There is currently no stable liquid form of glucagon commercially available. The aim of this study is to assess the speed of absorption and onset of action of G-Pump™ glucagon at 3 doses as compared to GlucaGen®, all delivered subcutaneously via an OmniPod®.

Methods: Nineteen adult subjects with type 1 diabetes participated in this Phase 2, randomized, double-blind, cross-over, pharmacokinetic/pharmacodynamic study. Subjects were given 0.3, 1.2, and 2.0 µg/kg each of G-Pump glucagon and GlucaGen via an OmniPod.

Results: G-Pump glucagon effectively increased blood glucose levels in a dose-dependent fashion with a glucose Cmax of 183, 200, and 210 mg/dL at doses of 0.3, 1.2, and 2.0 µg/kg, respectively (P = ns vs GlucaGen). Mean increases in blood glucose from baseline were 29.2, 52.9, and 77.7 mg/dL for G-Pump doses of 0.3, 1.2, and 2.0 µg/kg, respectively. There were no statistically significant differences between treatments in the glucose T50%-early or glucagon T50%-early with one exception. The glucagon T50%-early was greater following G-Pump treatment at the 2.0 μg/kg dose (13.9 ± 4.7 min) compared with GlucaGen treatment at the 2.0 μg/kg dose (11.0 ± 3.1 min, P = .018). There was more pain and erythema at the infusion site with G-Pump as compared to GlucaGen. No serious adverse events were reported, and no unexpected safety issues were observed.

Conclusions: G-Pump glucagon is a novel, stable glucagon formulation with similar PK/PD properties as GlucaGen, but was associated with more pain and infusion site reactions as the dose increased, as compared to GlucaGen.

Keywords: artificial pancreas; glucagon; hypoglycemia; type 1 diabetes.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / pharmacokinetics*
  • Glucagon / administration & dosage
  • Glucagon / adverse effects
  • Glucagon / pharmacokinetics*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Insulin Infusion Systems
  • Male
  • Middle Aged
  • Transdermal Patch
  • Young Adult

Substances

  • Blood Glucose
  • Gastrointestinal Agents
  • Hypoglycemic Agents
  • Insulin
  • Glucagon