Efficacy and Usability of Intranasal Glucagon for the Management of Hypoglycemia in Patients With Diabetes: A Systematic Review.

PURPOSE

Hypoglycemia is a common and sometimes life-threatening adverse event associated with insulin, sulfonylurea, and meglitinide therapies. In patients who are disoriented or unconscious, treatment with injectable glucagon is recommended, along with a call for emergency medical assistance. However, limitations of this formulation include difficulty with reconstitution and an unwillingness to administer an injection. In July 2019, intranasal glucagon was approved for use in the acute treatment of severe hypoglycemia in patients ≥4 years of age with diabetes. The purpose of this systematic review was to describe the efficacy, usability, and tolerability of intranasal glucagon 3 mg in patients with diabetes.

METHODS

To identify studies, the following databases were systematically searched: Ovid MEDLINE, Embase, CINAHL, Web of Science Core Collection, Cochrane CENTRAL (EBSCO), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, from inception to March 3, 2020. Comparative studies included patients with diabetes and an active comparator. Usability studies enrolled participants who used a device for glucagon administration.

FINDINGS

Ten studies met the inclusion criteria. In 5 comparative studies in insulin-induced hypoglycemia (intranasal vs injectable glucagon), the criteria for successful treatment varied. In 3 studies, it was defined as an increase in blood glucose of ≥70 mg/dL (3.9 mmol/L) or an increase of ≥20 mg/dL (1.1 mmol/L) within 30 min of glucagon administration. In 1 study, the criteria were stricter, with success defined as an increase in blood glucose of ≥27 mg/dL (≥1.5 mmol/L) within 15 min. In the pediatrics study, success was defined as an increase in blood glucose of ≥25 mg/dL (1.4 mmol/L) within 20 min. In 2 studies of intranasal glucagon monotherapy in clinical practice, the primary end point was the percentage of patients who awakened or returned to normal status within 30 min of intranasal glucagon administration. In these 7 studies, almost all of the participants met the criteria for success as defined in their respective studies. The mean time to treatment success was between 10 and 20 min with intranasal and injectable glucagon. Nausea and vomiting were common adverse events with both formulations; watery eyes and runny nose occurred more frequently with intranasal glucagon. In 3 simulation studies, caregivers and noncaregivers administered intranasal glucagon within 1 min versus 1.3-5 min with IM glucagon.

IMPLICATIONS

In patients who are disoriented or unconscious, treatment with injectable or ready-to-use intranasal glucagon increases blood glucose within 15-30 min. Intranasal glucagon was preferred by most caregivers and noncaregivers due to its ease of use. Additional studies of intranasal glucagon in younger patients (1-<3 years of age), pregnant women, and in comparison with SC glucagon are needed to further clarify bioavailability, efficacy, and tolerability.