title: Pharmacokinetic and Pharmacodynamic Properties of Faster-Acting Insulin Aspart versus Insulin Aspart Across a Clinically Relevant Dose Range in Subjects with Type 1 Diabetes Mellitus.
abstract: Absorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insulin aspart across a clinically relevant dose range.
  
  
  
  In this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster aspart and insulin aspart at 0.1, 0.2 (repeated three times to estimate within-subject variability) and 0.4 U/kg in a euglycaemic clamp setting (target 5.5 mmol/L).
  
  
  
  Consistently for the three doses, faster aspart demonstrated faster onset and greater early absorption and glucose-lowering effect versus insulin aspart. Across all three doses, onset of appearance occurred approximately twice as fast (approximately 5 min earlier) and early insulin exposure (AUCIAsp,0-30min) was approximately 1.5- to 2-fold greater for faster aspart versus insulin aspart. Likewise, onset of action occurred approximately 5 min faster and early glucose-lowering effect (AUCGIR,0-30min) was approximately 1.5- to 2-fold larger for faster aspart versus insulin aspart. Relative bioavailability was approximately 100% and total glucose-lowering effect was similar for faster aspart versus insulin aspart. Dose-concentration and dose-response relationships were comparable between faster aspart and insulin aspart. Within-subject variability in glucose-lowering effect was low for faster aspart (coefficient of variation approximately 20%) and not significantly different from insulin aspart.
  
  
  
  The faster onset and greater early insulin exposure and glucose-lowering effect with faster aspart versus insulin aspart are preserved across a broad range of doses and consistently observed from day to day. CLINICALTRIALS.
  
  
  
  NCT02033239.
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: Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Stender-Petersen
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, 41460, Neuss, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hövelmann
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
authors.forename: Jacob Bonde
authors.initials: JB
authors.lastname: Jacobsen
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, 41460, Neuss, Germany.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
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: Hanne
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D061267:Insulin Aspart / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D061267:Insulin Aspart