A new non-invasive method for treating insulin-reaction: intranasal lyophylized glucagon.
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.
Slama
G
G
Department of Diabetes, Hôtel-Dieu Hospital, Paris, France.
Alamowitch
C
C
Desplanque
N
N
Letanoux
M
M
Zirinis
P
P
D000281:Administration, Intranasal; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005612:Freeze Drying; D005934:Glucagon / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D007328:Insulin; D005934:Glucagon