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.

Trial registration: ClinicalTrials.gov NCT01997411.

© 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.

Figures

Figure 1

Study flowchart. aOne participant requested to withdraw prior to the second visit. IM, intramuscular; IN, intranasal; yrs, years.

Figure 2

A: Glucose and glucagon concentrations over time according to treatment arm: 4 to <8 years old. Solid black bars and line, 3 mg intranasal; solid white bars and long dashed line, 2 mg intranasal; horizontal black-and-white striped bars and short dashed line, intramuscular. B: Glucose and glucagon concentrations over time according to treatment arm: 8 to <12 years old. Solid black bars and line, 3 mg intranasal; solid white bars and long dashed line, 2 mg intranasal; horizontal black-and-white striped bars and short dashed line, intramuscular. C: Glucose and glucagon concentrations over time according to treatment arm: 12 to <17 years old. Solid black bars and line, 3 mg intranasal; horizontal black-and-white striped bars and short dashed line, intramuscular. Lab, laboratory.