title: Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics and pharmacodynamics of faster-acting insulin aspart and insulin aspart in a randomized, single-centre, double-blind study.
  
  
  METHODS
  Fifty-two patients with type 1 diabetes (mean age 40.3 years) received faster-acting insulin aspart, insulin aspart, or another faster aspart formulation (not selected for further development), each as a single 0.2 U/kg subcutaneous dose, under glucose-clamp conditions, in a three-way crossover design (3-12 days washout between dosing).
  
  
  RESULTS
  Faster-acting insulin aspart had a faster onset of exposure compared with insulin aspart, shown by a 57% earlier onset of appearance [4.9 vs 11.2 min; ratio 0.43, 95% confidence interval (CI) 0.36; 0.51], a 35% earlier time to reach 50% maximum concentration (20.7 vs 31.6 min; ratio 0.65, 95% CI 0.59; 0.72) and a greater early exposure within 90 min after dosing. The greatest difference occurred during the first 15 min, when area under the serum insulin aspart curve was 4.5-fold greater with faster-acting insulin aspart than with insulin aspart. Both treatments had a similar time to maximum concentration, total exposure and maximum concentration. Faster-acting insulin aspart had a significantly greater glucose-lowering effect within 90 min after dosing [largest difference: area under the curve for the glucose infusion rate (AUC(GIR), 0-30 min) ratio 1.48, 95% CI 1.13; 2.02] and 17% earlier time to reach 50% maximum glucose infusion rate (38.3 vs 46.1 min; ratio 0.83, 95% CI 0.73; 0.94). The primary endpoint (AUC(GIR, 0-2 h)) was 10% greater for faster-acting insulin aspart, but did not reach statistical significance (ratio 1.10, 95% CI 1.00; 1.22). Both treatments had similar total and maximum glucose-lowering effects, indicating similar overall potency.
  
  
  CONCLUSIONS
  Faster-acting insulin aspart was found to have earlier onset and higher early exposure than insulin aspart, and a greater early glucose-lowering effect, with similar potency.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Heise
authors.affiliation: Profil, Neuss, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hövelmann
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Brøndsted
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: C L
authors.initials: CL
authors.lastname: Adrian
authors.affiliation: Profil, Neuss, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Nosek
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D061267:Insulin Aspart / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D061267:Insulin Aspart
keywords: faster-acting insulin aspart; pharmacodynamics; pharmacokinetics; postprandial glucose; type 1 diabetes
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