title: Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Yale School of Medicine, New Haven, CT.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sherr
authors.affiliation: Jaeb Center for Health Research, Tampa, FL.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Ruedy
authors.affiliation: Jaeb Center for Health Research, Tampa, FL t1dstats@jaeb.org.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Foster
authors.affiliation: Locemia Solutions ULC, Montreal, Canada.
authors.forename: Claude A
authors.initials: CA
authors.lastname: Piché
authors.affiliation: Locemia Solutions ULC, Montreal, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dulude
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
authors.affiliation: Yale School of Medicine, New Haven, CT.
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.affiliation: University at Buffalo School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Bethin
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Linda A
authors.initials: LA
authors.lastname: DiMeglio
authors.affiliation: Nemours Children's Specialty Care, Jacksonville, FL.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Fox
authors.affiliation: Barbara Davis Center for Childhood Diabetes, Aurora, CO.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wadwa
authors.affiliation: University of Florida, Gainesville, FL.
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Schatz
authors.affiliation: University of Minnesota, Minneapolis, MN.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Nathan
authors.affiliation: Northwest Lipid Metabolism and Diabetes Research Laboratories, Seattle, WA.
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.affiliation: JSS Medical Research, Saint-Laurent, Canada.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Rampakakis
authors.affiliation: JSS Medical Research, Saint-Laurent, Canada.
authors.forename: Linyan
authors.initials: L
authors.lastname: Meng
authors.affiliation: Jaeb Center for Health Research, Tampa, FL.
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy; D007273:Injections, Intramuscular; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D008297:Male; D009325:Nausea / Q000209:etiology / Q000517:prevention & control; D011208:Powders
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011208:Powders; D005934:Glucagon