A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes

Clin Pharmacokinet. 2017 May;56(5):551-559. doi: 10.1007/s40262-017-0514-8.


Background: Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation aiming to mimic the fast endogenous prandial insulin release more closely than currently available insulin products. In a post hoc analysis of pooled data from six clinical pharmacology trials, the pharmacological characteristics of faster aspart and IAsp were compared.

Methods: The analysis included 218 adult subjects with type 1 diabetes from six randomised, double-blind, crossover trials in the faster aspart clinical development programme. Subjects received subcutaneous dosing (0.2 U/kg) of faster aspart and IAsp. In three trials, a 12-h euglycaemic clamp was performed (target 5.5 mmol/L; 100 mg/dL) to assess pharmacodynamics.

Results: The pharmacokinetic and pharmacodynamic profiles were left-shifted for faster aspart versus IAsp. Onset of appearance occurred 4.9 min earlier (95% confidence interval [CI] faster aspart-IAsp: [-5.3 to -4.4], p < 0.001), early exposure (AUCIAsp,0-30min) was two times greater (estimated ratio faster aspart/IAsp 2.01 [1.87-2.17], p < 0.001) and offset of exposure (t Late 50% Cmax) occurred 12.2 min earlier [-17.9 to -6.5] (p < 0.001) for faster aspart versus IAsp. Accordingly, onset of action occurred 4.9 min earlier [-6.9 to -3.0] (p < 0.001), early glucose-lowering effect (AUCGIR,0-30min) was 74% greater (1.74 [1.47-2.10], p < 0.001) and offset of glucose-lowering effect (t Late 50% GIRmax) occurred 14.3 min earlier [-22.1 to -6.5] (p < 0.001) for faster aspart versus IAsp. Total exposure and total glucose-lowering effect did not differ significantly between treatments.

Conclusions: Faster aspart has the potential to better mimic the physiologic prandial insulin secretion and thereby to improve postprandial glucose control compared with IAsp. ClinicalTrials.gov identifiers: NCT02035371, NCT01924637, NCT02131246, NCT02033239, NCT02003677, NCT01618188.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics*
  • Injections, Subcutaneous
  • Insulin Aspart / administration & dosage*
  • Insulin Aspart / pharmacokinetics*
  • Male
  • Randomized Controlled Trials as Topic / methods*


  • Hypoglycemic Agents
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT02035371
  • ClinicalTrials.gov/NCT02003677
  • ClinicalTrials.gov/NCT02131246
  • ClinicalTrials.gov/NCT01924637
  • ClinicalTrials.gov/NCT01618188
  • ClinicalTrials.gov/NCT02033239