title: Insulin degludec/insulin aspart in Japanese patients with type 1 diabetes mellitus: Distinct prandial and basal glucose-lowering effects.
abstract: OBJECTIVE
  Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). The present study investigated the pharmacodynamic properties of IDegAsp in Japanese patients with type 1 diabetes mellitus.
  
  
  METHODS
  In this randomized, double-blind, two-period, cross-over trial, 21 Japanese patients with type 1 diabetes mellitus received single doses of 0.5 U/kg IDegAsp and biphasic insulin aspart 30 in a randomized sequence (13-21 days washout between treatments). The pharmacodynamic response was evaluated in a 26-h euglycemic glucose clamp (target 5.5 mmol/L). Single-dose IDegAsp glucose infusion rate (GIR) profiles were extrapolated to steady state using modeling.
  
  
  RESULTS
  The IDegAsp single-dose GIR profile showed a clear distinction between the effects of the bolus (IAsp) and basal (IDeg) components in IDegAsp. When simulated to steady state, the GIR profile of IDegAsp was shifted upwards compared with the single-dose profile, and showed a rapid onset of action and a distinct peak from the IAsp component followed by a separate and sustained basal action from the long-acting IDeg component. For biphasic insulin aspart 30, the initial shape of the GIR profile was similar to IDegAsp, but GIR continuously decreased from maximum and reached zero 18-20 h post-dosing. The characteristics of the GIR profile for IDegAsp were retained when simulated to steady state in a twice-daily dosing regimen.
  
  
  CONCLUSIONS
  In Japanese patients with type 1 diabetes mellitus, the pharmacodynamic profile of IDegAsp is characterized by distinct prandial and basal effects from the IAsp and IDeg components, consistent with what has been reported previously in Caucasian patients with type 1 diabetes mellitus.
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
authors.affiliation: Novo Nordisk Pharma Ltd., Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Bardtrum
authors.affiliation: SOUSEIKAI, Sumida Hospital, Tokyo, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Ikushima
mesh_terms: D000328:Adult; D044466:Asian People; D061265:Biphasic Insulins / Q000493:pharmacokinetics / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061267:Insulin Aspart / Q000493:pharmacokinetics* / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged
chemical_list: D061265:Biphasic Insulins; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C578220:insulin degludec, insulin aspart drug combination; C571886:insulin degludec; D061267:Insulin Aspart; D005947:Glucose
keywords: Insulin degludec - insulin aspart; Japanese; Pharmacodynamics