title: A Comparison of Pharmacokinetic and Pharmacodynamic Properties Between Faster-Acting Insulin Aspart and Insulin Aspart in Elderly Subjects with Type 1 Diabetes Mellitus.
abstract: Due to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption. This study investigated the pharmacological properties of faster aspart in elderly subjects with type 1 diabetes mellitus (T1DM).
  
  
  
  In a randomised, double-blind, two-period crossover trial, 30 elderly (≥65 years) and 37 younger adults (18-35 years) with T1DM received single subcutaneous faster aspart or IAsp dosing (0.2 U/kg) and underwent an euglycaemic clamp (target 5.5 mmol/L) for up to 12 h.
  
  
  
  The pharmacokinetic and pharmacodynamic time profiles were left-shifted for faster aspart versus IAsp. In each age group, onset of appearance occurred approximately twice as fast (~3 min earlier) and early exposure (area under the concentration-time curve [AUC] for serum IAsp from time zero to 30 min [AUCIAsp,0-30 min]) was greater (by 86% in elderly and 67% in younger adults) for faster aspart than for IAsp. Likewise, onset of action occurred 10 min faster in the elderly and 9 min faster in younger adults, and early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 30 min [AUCGIR,0-30 min]) was greater (by 109%) for faster aspart than for IAsp in both age groups. Total exposure (AUCIAsp,0-t) and the maximum concentration (Cmax) for faster aspart were greater (by 30 and 28%, respectively) in elderly than in younger adults. No age group differences were seen for the total (AUCGIR,0-t) or maximum (GIRmax) glucose-lowering effect.
  
  
  
  This study demonstrated that the ultra-fast pharmacological properties of faster aspart are similar in elderly subjects and younger adults with T1DM. ClinicalTrials.gov Identifier: NCT02003677.
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstraße 9, 41460, Neuss, Germany. tim.heise@profil.com.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstraße 9, 41460, Neuss, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hövelmann
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstraße 9, 41460, Neuss, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Zijlstra
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Stender-Petersen
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
authors.forename: Jacob Bonde
authors.initials: JB
authors.lastname: Jacobsen
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061266:Insulin, Short-Acting / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D061266:Insulin, Short-Acting; D061267:Insulin Aspart