title: Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study.
abstract: OBJECTIVE
  Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia.
  
  
  METHODS
  At eight clinical centers, a randomized crossover noninferiority trial was conducted involving 75 adults with type 1 diabetes (mean age, 33 ± 12 years; median diabetes duration, 18 years) to compare intranasal (3 mg) versus intramuscular (1 mg) glucagon for treatment of hypoglycemia induced by intravenous insulin. Success was defined as an increase in plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the glucose nadir within 30 min after receiving glucagon.
  
  
  RESULTS
  Mean plasma glucose at time of glucagon administration was 48 ± 8 and 49 ± 8 mg/dL at the intranasal and intramuscular visits, respectively. Success criteria were met at all but one intranasal visit and at all intramuscular visits (98.7% vs. 100%; difference 1.3%, upper end of 1-sided 97.5% CI 4.0%). Mean time to success was 16 min for intranasal and 13 min for intramuscular (P < 0.001). Head/facial discomfort was reported during 25% of intranasal and 9% of intramuscular dosing visits; nausea (with or without vomiting) occurred with 35% and 38% of visits, respectively.
  
  
  CONCLUSIONS
  Intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. Although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response.
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
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, QC, Canada.
authors.forename: Claude A
authors.initials: CA
authors.lastname: Piché
authors.affiliation: Locemia Solutions ULC, Montreal, QC, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dulude
authors.affiliation: Yale School of Medicine, New Haven, CT.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sherr
authors.affiliation: Yale School of Medicine, New Haven, CT.
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.affiliation: Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 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: Barbara Davis Center for Childhood Diabetes, Aurora, CO.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wadwa
authors.affiliation: Harold Schnitzer Diabetes Health Center, Oregon Health & Science University, Portland, OR.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ahmann
authors.affiliation: University of Florida, Gainesville, FL.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Haller
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, St. Laurent, QC, Canada.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Rampakakis
authors.affiliation: JSS Medical Research, St. Laurent, QC, 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; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000008:administration & dosage*; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D005934:Glucagon