Pharmacological properties of faster-acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: A randomized, double-blind, crossover trial.
AIM
To evaluate the pharmacological characteristics of faster-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) during continuous subcutaneous insulin infusion (CSII).


METHODS
In this randomized, double-blind, crossover trial, 48 men and women aged 18 to 64 years with type 1 diabetes mellitus (T1DM) received faster aspart and IAsp as a 0.15 U/kg bolus dose via CSII, on top of a basal rate (0.02 U/kg/h), in a glucose clamp setting (target 5.5 mmol/L).


RESULTS
After a CSII bolus dose, the pharmacokinetic/pharmacodynamic profiles for faster aspart were left-shifted compared with those for IAsp. For faster aspart vs IAsp, the early glucose-lowering effect (area under the curve for glucose infusion rate [GIR]0-30min ) was approximately 2-fold higher (least squares means 24.9 vs 11.4 mg/kg; estimated ratio faster aspart/IAsp 2.18, 95% confidence interval [CI] [1.33; 5.04]; P = .002), onset of glucose-lowering effect (time to early 50% of maximum GIR) occurred 11.1 minutes earlier (41.1 vs 52.3 minutes; 95% CI faster aspart - IAsp [-15.4; -6.9]; P<.001), and offset of glucose-lowering effect (time to late 50% of maximum GIR) occurred 24.0 minutes earlier (214.7 vs 238.7 minutes; 95% CI [-38.9; -9.1]; P=.002). Likewise, significantly greater early exposure and significantly earlier onset and offset of exposure were observed for faster aspart vs IAsp. Faster aspart and IAsp were both well tolerated.


CONCLUSIONS
In patients with T1DM using CSII, faster aspart better mimics the endogenous prandial insulin secretion and action than does IAsp. Faster aspart therefore has the potential to provide clinical benefits over current rapid-acting insulins in the insulin pump setting.
['Heise|Tim|T|', 'Zijlstra|Eric|E|', 'Nosek|Leszek|L|', 'Rikte|Tord|T|', 'Haahr|Hanne|H|']
D000328:Adult D019540:Area Under Curve D001786:Blood Glucose D018592:Cross-Over Studies D003922:Diabetes Mellitus, Type 1 D004311:Double-Blind Method D005260:Female D015309:Glucose Clamp Technique D006801:Humans D007004:Hypoglycemic Agents D055104:Infusions, Subcutaneous D061267:Insulin Aspart D007332:Insulin Infusion Systems D016018:Least-Squares Analysis D008297:Male D008875:Middle Aged
type 1 diabetes pharmacokinetics pharmacodynamics insulin pump therapy