Larry C. Deeb
Children with type 1 diabetes who experienced a moderate hypoglycemic event returned to euglycemic status within 30 minutes of receiving nasal glucagon from a caregiver in a real-world setting, according to findings from a phase 3 study published in Pediatric Diabetes.
Glucagon, one of the first-line treatments for severe hypoglycemia in a real-world setting, is unstable in an aqueous form. Available kits contain powdered glucagon that must be reconstituted in a multistep process before the drug can be administered to a patient, Larry C. Deeb, MD, a specialist in pediatric endocrinology at Tallahassee Memorial Healthcare, Florida, and colleagues wrote in the study background. A caregiver may also be required to decide on the correct dose to administer to a child based on his or her body weight.
“Although glucagon has been used for decades for the treatment of severe hypoglycemia and has a well-established efficacy and safety profile, nonmedical caregivers who need to administer this injection to a child with severe hypoglycemia in a stressful situation may find this procedure of reconstitution and injection intimidating,” the researchers wrote. “The complexity of administration may result in suboptimal use and reduced real-life effectiveness of glucagon. Currently, there exists an unmet need for a simple and easy-to-use glucagon formulation that can be used by nonmedical caregivers when confronted with a severe hypoglycemia situation.”
In a phase 3, open-label, prospective study, Deeb and colleagues analyzed data from 26 healthy children with type 1 diabetes for at least 1 year and their caregivers. Caregivers completed a hypoglycemia awareness survey at screening. Researchers trained caregivers to administer 3-mg nasal glucagon (Eli Lilly) to participating children during spontaneous, symptomatic moderate or severe hypoglycemic events at home or school and observe the treatment response, which was defined as awakening or returning to normal status within 30 minutes. Caregivers then measured blood glucose in treated children every 15 minutes. Parents completed the Hypoglycemia Episode Questionnaire, the Nasal Score Questionnaire and a User-Friendliness Assessment Questionnaire to assess ease-of-use and report adverse events. Primary outcome was the proportion of patients who awakened or returned to a normal status within 30 minutes after nasal glucagon administration. Other outcomes assessed included change in blood glucose level at 15, 30 and 45 minutes, safety, tolerability and ease-of-use. All outcomes were based on patient and caregiver-reported data.
Within the cohort, 11 patients were from a site deemed noncompliant with good clinical practice and were excluded from the analysis. The analysis population included 14 patients who experienced 33 moderate hypoglycemic events with neuroglycopenic symptoms, with a blood glucose level less than 70 mg/dL (mean age, 10 years; 64.3% boys; 100% white; mean diabetes duration, 6.3 years; 71.4% on pump therapy; mean total daily insulin dose, 42.3 U). Three of the patients reported experiencing severe hypoglycemia in the preceding year.
For all 33 hypoglycemic events, patients returned to normal status within 30 minutes of nasal glucagon administration. Mean blood glucose for the cohort increased from 55.5 mg/dL (range, 42-70 mg/dL) at baseline to 113.7 mg/dL (range, 79-173 mg/dL) within 15 minutes of nasal glucagon administration. No additional emergency health services, oral carbohydrates or injectable glucagon were required for patients, according to the researchers.
For 93.9% of the hypoglycemic events, caregivers reported that nasal glucagon administration was “easy” or “very easy.” For 60.6% of events, caregivers administered nasal glucagon within 30 seconds. There were no serious adverse events.
“The ease of administration of needle-free [nasal glucagon] as compared with the injectable formulations may make it a preferred treatment option for nonmedical caregivers of pediatric patients with [type 1 diabetes],” the researchers wrote. – by Regina Schaffer
Disclosures: Eli Lilly and Locemia Solutions funded this study. Six of the study authors report being employees and stockholders at Eli Lilly or Locemia Solutions.