Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes.

Abstract

OBJECTIVE:

Treatment of severe hypoglycemia outside of the hospital setting is limited to intramuscular glucagon requiring reconstitution prior to injection. The current study examined the safety and dose-response relationships of a needle-free intranasal glucagon preparation in youth aged 4 to <17 years.

RESEARCH DESIGN AND METHODS:

A total of 48 youth with type 1 diabetes completed the study at seven clinical centers. Participants in the two youngest cohorts (4 to <8 and 8 to <12 years old) were randomly assigned to receive either 2 or 3 mg intranasal glucagon in two separate sessions or to receive a single, weight-based dose of intramuscular glucagon. Participants aged 12 to <17 years received 1 mg intramuscular glucagon in one session and 3 mg intranasal glucagon in the other session. Glucagon was given after glucose was lowered to <80 mg/dL (mean nadir ranged between 67 and 75 mg/dL).

RESULTS:

All 24 intramuscular and 58 of the 59 intranasal doses produced a ≥25 mg/dL rise in glucose from nadir within 20 min of dosing. Times to peak plasma glucose and glucagon levels were similar under both intramuscular and intranasal conditions. Transient nausea occurred in 67% of intramuscular sessions versus 42% of intranasal sessions (P = 0.05); the efficacy and safety of the 2- and 3-mg intranasal doses were similar in the youngest cohorts.

CONCLUSIONS:

Results of this phase 1, pharmacokinetic, and pharmacodynamic study support the potential efficacy of a needle-free glucagon nasal powder delivery system for treatment of hypoglycemia in youth with type 1 diabetes. Given the similar frequency and transient nature of adverse effects of the 2- and 3-mg intranasal doses in the two youngest cohorts, a single 3-mg intranasal dose appears to be appropriate for use across the entire 4- to <17-year age range.

• Authors: Jennifer L Sherr, Katrina J Ruedy, Nicole C Foster, Claude A Piché, Hélène Dulude, Michael R Rickels, William V Tamborlane, Kathleen E Bethin, Linda A DiMeglio, Larry A Fox, R Paul Wadwa, Desmond A Schatz, Brandon M Nathan, Santica M Marcovina, Emmanouil Rampakakis, Linyan Meng, Roy W Beck, T1D Exchange Intranasal Glucagon Investigators
• Journal: Diabetes care (Diabetes Care) Vol. 39 Issue 4 Pg. 555-62 (Apr 2016) ISSN: 1935-5548 [Electronic] United States
• PMID: 26884472 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Blood Glucose
• Insulin
• Powders
• Glucagon

Topics

• Administration, Intranasal
• Adolescent
• Blood Glucose (metabolism)
• Child
• Child, Preschool
• Cohort Studies
• Cross-Over Studies
• Diabetes Mellitus, Type 1 (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug-Related Side Effects and Adverse Reactions (prevention & control)
• Female
• Glucagon (administration & dosage, adverse effects)
• Humans
• Hypoglycemia (blood, drug therapy)
• Injections, Intramuscular
• Insulin (blood, therapeutic use)
• Male
• Nausea (etiology, prevention & control)
• Powders