Background: A room-temperature stable, soluble liquid glucagon formulation loaded into a prefilled, single-use, two-step autoinjector is under development for severe hypoglycemia rescue. We report a human factors validation program evaluating the glucagon autoinjector (GAI) (Gvoke HypoPen™; Xeris Pharmaceuticals, Inc., Chicago, IL) versus marketed glucagon emergency kits (GEKs) for managing severe hypoglycemia. Methods: A simulated-use human factors usability study was conducted with the GAI versus marketed GEKs in 16 participants, including adult caregivers and first responders, experienced with glucagon administration. A summative human factors validation study of the GAI was conducted with 75 volunteers. Participants were (1) trained on the device and procedure or (2) given time to individually read the instructions and familiarize themselves with the device. Participants returned a week later to perform an unaided rescue attempt that simulated rescue of patients with diabetes suffering a hypoglycemia emergency. Participant actions were recorded for critical rescue tasks and use errors. Results: In the usability study, 88% (14) successfully administered a rescue injection using the GAI versus 31% (5) using GEKs ( P < 0.05). Mean total rescue time of use was 47.9 s with the GAI versus 109.0 s with GEKs ( P < 0.05). In the validation study, 98.7% successfully administered the rescue injection using the GAI. Overall, there were no patterns of differences between trained versus untrained participants, between caregivers versus first responders or between adults versus adolescents. Conclusion: The GAI and instructional materials can be correctly, safely, and effectively used by intended user, which support continued development of the GAI as an alternative to GEKs.

SymposiumGlucagon is currently approved for the treatment of severe hypoglycemia.1,2 Because glucagon is not stable in aqueous solutions, these preparations are provided as lyophilized powders for reconstitution. Once reconstituted, these preparations begin to degrade and fibrillate rapidly and must be discarded if not used immediately. While suitable for treatment of severe hypoglycemia, these glucagon preparations are unstable and thus not suitable for development of additional indications including minidosing for mild to moderate hypoglycemia 3 and infusion pump applications. In particular, a stable glucagon suitable for use in infusion pump systems creates an opportunity for treatment of hypoglycemia under different conditions, including as a component of an artificial or "bionic" pancreas system. 4,5Despite a vigorous research effort, to date development of aqueous-based glucagon formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability (up to 2 years at room temperature) 6 at relatively high concentrations.The solubility and stability of this formulation allow for development of a higher concentration formulation (5 mg/ml vs 1 mg/ml for the currently approved glucagon formulations) to facilitate administration from devices such as autoinjectors, pens, pumps, and so on. Furthermore, this glucagon formulation is in clinical development as a treatment for severe hypoglycemia 6 and moderate hypoglycemia and for management of blood glucose in pump applications.This article presents stability, compatibility, and preclinical data supporting progression of this formulation into clinical development. Background: Despite a vigorous research effort, to date, the development of systems that achieve glucagon stability in aqueous formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability at relatively high concentrations and at high temperatures.

MDG may be more effective than insulin reduction for preventing exercise-induced hypoglycemia and may result in less postintervention hyperglycemia than ingestion of carbohydrate.

Low-dose glucagon can successfully treat mild hypoglycemia and may be a useful alternative to treatment with oral carbohydrate when trying to avoid unnecessary caloric intake.