title: Distinct Prandial and Basal Glucose-Lowering Effects of Insulin Degludec/Insulin Aspart (IDegAsp) at Steady State in Subjects with Type 1 Diabetes Mellitus.
abstract: OBJECTIVE
  Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of long-acting and short-acting insulin analogs. The primary objective of this study was to investigate the pharmacodynamic response of once-daily IDegAsp dosing in patients with type 1 diabetes. Pharmacokinetic response, as well as safety and tolerability, were assessed as secondary objectives.
  
  
  METHODS
  This was a single-center, open-label, single-arm study. Twenty-two subjects received once-daily insulin degludec (IDeg) (0.42 U/kg) for five consecutive days [with separate bolus insulin aspart (IAsp) as needed for safety and glycemic control], to achieve clinical steady state of the basal component. On Day 6, they received a single injection of IDegAsp (0.6 U/kg, comprising 0.42 U/kg IDeg and 0.18 U/kg IAsp). Pharmacodynamic response was assessed using a 30-h euglycemic glucose clamp, with blood glucose stabilized at a target of 5.5 mmol/L.
  
  
  RESULTS
  The glucose infusion rate profile showed a rapid onset of action and a distinct peak due to IAsp, followed by a separate, flat and stable basal glucose-lowering effect due to the IDeg component. Modeling data suggested that the pharmacodynamic profile of IDegAsp was retained with twice-daily dosing (allowing for coverage of two main meals daily). IDegAsp was well tolerated and no safety issues were identified in this trial.
  
  
  CONCLUSIONS
  In conclusion, the IAsp component of IDegAsp has a fast onset of appearance and a peak covering the prandial phase, while the IDeg component has a flat and an evenly distributed pharmacokinetic profile over 24 h. IDegAsp is the first co-formulation of a basal insulin analog with an ultra-long duration of action and a mealtime insulin analog in a single soluble injection. These properties translate into clinically relevant benefits, including improved glycemic control and reduction in hypoglycemia.
authors.affiliation: Profil Institute for Metabolic Research, Hellersbergstr. 9, 41460, Neuss, Germany, tim.heise@profil.com.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.forename: Carsten
authors.initials: C
authors.lastname: Roepstorff
authors.forename: Suresh
authors.initials: S
authors.lastname: Chenji
authors.forename: Oliver
authors.initials: O
authors.lastname: Klein
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr