A new non-invasive method for treating insulin-reaction: intranasal lyophylized glucagon

Diabetologia. 1990 Nov;33(11):671-4. doi: 10.1007/BF00400568.

Abstract

The main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 (insulin-dependent) diabetic patients. We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v. insulin-induced hypoglycaemia in diabetic patients. However, bioavailability and stability needed to be improved before intranasal glucagon could be introduced into clinical practice. This has now been achieved with a freeze-dried mixture of glucagon (1 mg) and glycocholic acid (1 mg) as a surfactant. Kinetics and efficacy have been controlled by (1) comparing subcutaneous and intranasal glucagon in 12 healthy non-hypoglycaemic subjects; (2) testing intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by an i.v. bolus of insulin and (3) comparing subcutaneous and intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by adding extra subcutaneous regular insulin to their usual morning dosage. Our results show that 1 mg of intranasal glucagon is as effective as 1 mg of subcutaneous glucagon in terms of the rise in blood glucose. Differences in kinetics between the subcutaneous and the intranasal routes may be observed: intranasal glucagon initiates the blood glucose rise earlier than does the subcutaneous form but the effect of the latter is more sustained. Glycocholic acid appears to be a perfectly tolerated agent in acute conditions. The use of intranasal lyophylized glucagon, for the reversal of hypoglycaemia in Type 1 diabetes, seems to be a clinically relevant alternative to its parenteral equivalent and should now be ready to be introduced in the market.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Administration, Intranasal
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dose-Response Relationship, Drug
  • Freeze Drying
  • Glucagon / administration & dosage
  • Glucagon / therapeutic use*
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / drug therapy*
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / therapeutic use*

Substances

  • Insulin
  • Glucagon