Glucose-Responsive Glucagon Formulations for Closed-Loop Prophylactic Treatment of Hypoglycemia

Insulin therapy revolutionized the care of parents with diabetes, yet insulin-induced hypoglycemia remains a serious life-threatening complication of insulin therapy. Glucagon is a highly effective treatment for hypoglycemia; however, current dosage forms remain under-utilized due to poor patient compliance. High-density, readily soluble, and thermostable solid glucagon formulations applied with painless, application-specific microneedle-patches can treat hypoglycemia in type 1 diabetes patients who are awake or asleep. On-demand patches can prevent or treat mild hypoglycemia during the day, and enzyme-driven hypoglycemia-responsive patches can release glucagon autonomously during the night. These patches have excellent in vitro glucagon stability. loading, and release kinetics and can treat hypoglycemia in diabetic humans and animals. These delivery systems enable new modes of glucagon therapy, thereby expanding the clinical role of glucagon beyond the emergency setting.