Glucagon Administration by Nasal and Intramuscular Routes in Adults With Type 1 Diabetes During Insulin-Induced Hypoglycaemia: A Randomised, Open-Label, Crossover Study

Abstract

Introduction: Many commercially available glucagon products for treatment of severe hypoglycaemia require cumbersome reconstitution and potentially intimidating injection during an emergency. Nasal glucagon (NG) is a novel drug-device combination product consisting of a single-use dosing device that delivers glucagon dry powder through nasal administration. The present study assessed whether 3 mg NG was non-inferior to 1 mg intramuscular glucagon (IMG) in adults with type 1 diabetes.

Methods: This randomised, open-label, two-period, crossover trial was conducted at two clinical sites. Hypoglycaemia (plasma glucose [PG] target of < 3.3 mmol/l (60 mg/dl) was induced by an intravenous insulin infusion. Glucagon preparations were given by study staff. Treatment success was defined as an increase in PG to ≥ 3.9 mmol/l (70 mg/dl) or an increase of ≥ 1.1 mmol/l (20 mg/dl) from the PG nadir within 30 min of receiving glucagon.

Results: Of the 66 participants included in the primary efficacy analysis who received both NG and IMG, 100% achieved treatment success, thus demonstrating non-inferiority of NG to IMG. All participants achieved treatment success within 25 min with the mean time to treatment success of 11.4 min (NG) and 9.9 min (IMG). No serious adverse events occurred. Forty-eight treatment-emergent adverse events (TEAEs) occurred after NG and 51 after IMG. Most TEAEs were mild and transient.

Conclusion: Nasal glucagon was as efficacious and well tolerated as IMG for the treatment of insulin-induced hypoglycaemia in adults and will be as useful as IMG as a rescue treatment for severe hypoglycaemia.

Trial registration: NCT03339453, ClinicalTrials.gov.

Keywords: Insulin-induced hypoglycaemia; Intramuscular glucagon; Nasal glucagon; Type 1 diabetes.

Figures

Fig. 1

Kaplan-Meier curve for the time to treatment success (an increase in PG to ≥ 3.9 mmol/l [70 mg/dl] or a PG increase of ≥ 1.1 mmol/l [20 mg/dl] from nadir) within 30 min following 3 mg nasal glucagon and 1 mg GlucaGen® treatment in participants who completed all dosing visits. Red line = 3 mg nasal glucagon (N = 68); black line = 1 mg intramuscular glucagon (N = 69). IM intra-muscular, PG plasma glucose

Fig. 2

a Arithmetic mean (± SD) profile of plasma glucose concentration after a single dose of 3 mg NG or 1 mg IMG. Red circles and line = 3 mg nasal glucagon (N = 68; baseline mean PG = 3.2 mmol/l; SD = 0.3); white circle and black line = 1 mg intramuscular glucagon (N = 69; baseline mean PG = 3.2 mmol/l; SD = 0.3). b Change from baseline plasma glucagon concentration (±SD) following single doses of 3 mg nasal glucagon or 1 mg GlucaGen. Red circles and line = 3 mg nasal glucagon (N = 68); white circle and black line = 1 mg intramuscular glucagon (N = 69). min minutes, SD standard deviation