By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a noninjectable, needle-free glucagon for the treatment of severe hypoglycemia. Baqsimi is an intranasal device that delivers glucagon powder.

INDICATIONS

Glucagon nasal powder (GNP) is indicated for the treatment of severe hypoglycemia in patients (≥ 4 years of age) with diabetes.1

DOSAGE

The recommended dose is 3 mg (one actuation of the intranasal device) into one nostril.1 GNP is available as an intranasal device containing a single dose of 3 mg of glucagon.

POTENTIAL ADVANTAGES

This formulation provides a more convenient administration of glucagon compared to the current emergency kit that requires mixing and injection. GNP is easier to administer with fewer failures for nonmedically trained individuals.2 The frequency of nausea may be lower with intranasal vs. intramuscular administration.

POTENTIAL DISADVANTAGES

Most frequent (> 30%) adverse reactions are watery eyes, nasal congestion, nasal itching, and runny nose.1 When administered by trained healthcare professionals in a nonemergency setting, there is a slight delay in glycemic response as symptoms of hypoglycemia were greater in the intranasal group for the first 45 minutes.3 Glucose concentration lagged in the intramuscular group administration by about five minutes.

COMMENTS

The efficacy of intranasal vs. intramuscular glucagon was evaluated in three studies. The first study was a randomized, open-label, crossover study of adults with type 1 diabetes (n = 66), the second study included both type 1 and type 2 diabetic adults (n = 80), and the third study was conducted with pediatric type 1 diabetes subjects (age 4 years up to < 17 years of age; n = 48).1,3,4

In both adult studies, hypoglycemia was induced by insulin, to < 60 mg/dL in the first study and < 50 mg/dL in the second study. Subjects were randomized to 3 mg of intranasal glucagon or 1 mg of intramuscular glucagon and then crossed over to the other treatment one to four weeks apart. Treatment success was defined as either an increase in blood glucose to ≥ 70 mg/dL or an increase of ≥ 20 mg/dL from glucose nadir within 30 minutes after administration. Treatment success was 100% for both formulations in study 1 and 98.8% for intranasal glucagon and 100% for intramuscular glucagon in study 2.

In the pediatric study, subjects received either 2 mg or 3 mg of intranasal glucagon or a dose of weight-based (0.5 mg or 1 mg) intramuscular glucagon. All subjects who received intramuscular glucagon (24/24) or 3 mg of intranasal glucagon (36/36) achieved a blood glucose level ≥ 20 mg/dL within 30 minutes.4 Mean times to achieving glucose ≥ 20 mg/dL ranged from 10.8 minutes to 14.2 minutes.1 Nausea, with or without vomiting, tended to be less frequent with intranasal vs. intramuscular glucagon.

In two real-world studies, one that included adults and one that included a pediatric population, intranasal glucagon was effective, generally well tolerated, and easy to use.5,6 In a simulation study (administered to manikin), > 90% of instructed caregivers delivered the full dose of intranasal glucagon vs. 13% for intramuscular glucagon.2 Common cold and concomitant use of nasal decongestant do not significantly alter the effect of intranasal glucagon.7 The cost for both formulations is the same ($280.80 per unit).

CLINICAL IMPLICATIONS

The American Diabetes Association recommends glucose intake to treat hypoglycemia (e.g., 15 g of glucose and check in 15 minutes).8 For severe hypoglycemia (too long to treat with glucose), glucagon injection is recommended. This requires reconstitution and administration by injection. Intranasal glucagon offers the first glucagon formulation for emergency treatment that can be administered without an injection. It appears to be an easier-to-use, needle-free, equally effective alternative to injectable glucagon.

REFERENCES

  1. Lilly USA, LLC. Baqsimi Prescribing Information, July 2019. Available at: http://bit.ly/2TdsV4M. Accessed Aug. 8, 2019.
  2. Yale JF, Dulude H, Egeth M, et al. Faster use and fewer failures with needle-free nasal glucagon versus injectable glucagon in severe hypoglycemia rescue: A simulation study. Diabetes Technol Ther 2017;19:423-432.
  3. Rickels MR, Ruedy KJ, Foster NC, et al. Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: A randomized crossover noninferiority study. Diabetes Care 2016;39:264-270.
  4. Sherr JL, Ruedy KJ, Foster NC, et al. Glucagon nasal powder: A promising alternative to intramuscular glucagon in youth with type 1 diabetes. Diabetes Care 2016;39:555-562.
  5. Deeb LC, Dulude H, Guzman CB, et al. A phase 3 multicenter, open-label, prospective study designed to evaluate the effectiveness and ease of use of nasal glucagon in the treatment of moderate and severe hypoglycemia in children and adolescents with type 1 diabetes in the home or school setting. Pediatr Diabetes 2018;19:1007-1013.
  6. Seaquist ER, Dulude H, Zhang XM, et al. Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real-world setting. Diabetes Obes Metab 2018;20:1316-1320.
  7. Guzman CB, Dulude H, Piché C, et al. Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial. Diabetes Obes Metab 2018;20:646-653.
  8. American Diabetes Association. Hypoglycemia (Low Blood Glucose). Available at: http://bit.ly/2YL8wcL. Accessed Aug. 8, 2019.