Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart.

Introduction: Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with two added excipients (niacinamide and L-arginine) in order to obtain accelerated absorption after subcutaneous dosing. The present study compared the pharmacokinetic/pharmacodynamic characteristics of faster aspart vs IAsp in Japanese patients with type 1 diabetes.

Materials And Methods: In a randomized, double-blind, cross-over design, 43 participants were given faster aspart and IAsp (0.2 U/kg single dose) at two separate dosing visits. Frequent pharmacokinetic blood sampling was carried out, and pharmacodynamics were assessed using an automated euglycemic clamp lasting for a maximum of 12 h after dosing (target 5.5 mmol/L).

Results: Faster aspart showed onset of appearance approximately twice-as-fast vs IAsp (least squares means: 3.0 vs 7.1 min; estimated treatment difference -4.1 min, 95% confidence interval [CI]: -5.0, -3.2; P < 0.001) and onset of action occurring approximately 5 min earlier (20.2 vs 25.5 min; estimated treatment difference -5.3 min, 95% CI: -8.4, -2.2; P = 0.001). Within the first 30 min post-dose, both exposure (area under the curve [AUC] ) and glucose-lowering effect (AUC ) were approximately twofold greater for faster aspart vs IAsp (P < 0.001 and P = 0.002, respectively). Bioavailability of faster aspart was similar to IAsp (AUC ; estimated treatment ratio 0.99, 90% CI: 0.96-1.02), whereas the total glucose-lowering effect (AUC ) was slightly lower for faster aspart vs IAsp (estimated treatment ratio 0.93, 95% CI: 0.87-0.99, P = 0.020).

Conclusions: Faster aspart showed faster onset, higher early exposure and a greater early glucose-lowering effect relative to IAsp in Japanese patients with type 1 diabetes, in accordance with previous findings in Caucasian type 1 diabetes patients.