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



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.



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.



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.
Department of Medicine, Division of Endocrinology, Harold Schnitzer Diabetes Health Center Oregon Health & Science University, Portland, OR, USA castleje@ohsu.edu.
Jessica R
JR
Castle
Department of Medicine, Division of Endocrinology, Harold Schnitzer Diabetes Health Center Oregon Health & Science University, Portland, OR, USA.
Joseph El
JE
Youssef
Department of Medicine, Division of Endocrinology, Harold Schnitzer Diabetes Health Center Oregon Health & Science University, Portland, OR, USA.
Deborah
D
Branigan
Xeris Pharmaceuticals, Inc, Austin, TX, USA.
Brett
B
Newswanger
Xeris Pharmaceuticals, Inc, Austin, TX, USA Integrated Medical Development, Princeton Junction, NJ, USA.
Poul
P
Strange
Xeris Pharmaceuticals, Inc, Austin, TX, USA.
Martin
M
Cummins
Integrated Medical Development, Princeton Junction, NJ, USA.
Leon
L
Shi
Xeris Pharmaceuticals, Inc, Austin, TX, USA.
Steven
S
Prestrelski
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005934:Glucagon / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D057968:Transdermal Patch; D055815:Young Adult
D001786:Blood Glucose; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon
artificial pancreas; glucagon; hypoglycemia; type 1 diabetes