Abstract
Episodes of hypoglycemia are frequent in patients with diabetes treated with insulin or sulphonylureas. Hypoglycemia can lead to severe acute complications, and, as such, both prevention and treatment of hypoglycemia are important for the well-being of patients with diabetes. The experience of hypoglycemia also leads to fear of hypoglycemia, that in turn can limit optimal glycemic control in patients, especially with type 1 diabetes. Treatment of hypoglycemia is still based on administration of carbohydrates (oral or parenteral according to the level of consciousness) or of glucagon (intramuscular or subcutaneous injection). In 1983, it was shown for the first time that intranasal (IN) glucagon drops (with sodium glycocholate as a promoter) increase blood glucose levels in healthy volunteers. During the following decade, several authors showed the efficacy of IN glucagon (drops, powders, and sprays) to resolve hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. Only in 2010, based on evaluation of patients’ beliefs and patients’ expectations, a canadian pharmaceutical company (Locemia Solutions, Montreal, Canada) reinitiated efforts to develop glucagon for IN administration. The project has been continued by Eli Lilly, that is seeking to obtain registration in order to make IN glucagon available to insulin users (children and adolescents) worldwide. IN glucagon is as effective as injectable glucagon, and devoid of most of the technical difficulties associated with administration of injectable glucagon. IN glucagon appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both children and adults.
Highlights
Intranasal Administration of Peptide HormonesPeptide hormones are traditionally administered by the parenteral route, be it by SC, IM or intravenous (IV) injection, as oral administration is precluded by digestion and inactivation in the gastrointestinal tract [20]
Treatment of diabetes mellitus has substantially changed over the last 20 years for both patients with type 1 (T1D) and type 2 (T2D) diabetes
IN glucagon is as effective as injectable glucagon, and devoid of most of the technical difficulties associated with administration of injectable glucagon
Summary
Peptide hormones are traditionally administered by the parenteral route, be it by SC, IM or intravenous (IV) injection, as oral administration is precluded by digestion and inactivation in the gastrointestinal tract [20]. Attempts to identify alternative routes of administration have been tested since the early 1920s, in particular for hormones that require life-long treatments, such as insulin [21,22]. In laboratory animals, intranasally administered insulin has been shown to exert effects opposite to parenteral insulin administration. This means that insulin in the brain regulates peripheral insulin sensitivity [26], and IN insulin induces insulin sensitivity in lean and obese subjects [27]. Intranasal insulin administration has been used to induce immune tolerance in T1D subjects [28], and GLP-1 has been administered IN to modify learning and for neuroprotection [29,30]
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