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. Issue 2 (7th July 2017) - Shiramoto, Masanari
Abstract : This study compared the pharmacokinetic/pharmacodynamic characteristics of faster aspart vs IAsp in Japanese patients with type 1 diabetes. Faster aspart demonstrated faster onset, higher early exposure and greater early glucose‐lowering effect vs IAsp. The accelerated absorption profile for faster aspart relative to IAsp in Japanese patients is in line with previous findings in Caucasians. Abstract: 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]IA sp, 0–30 min ) and glucose‐lowering effect (AUCGIR, 0–30 min ) 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 (AUCIA sp, 0‐t ; estimated treatment ratio 0.99, 90% CI: 0.96–1.02), whereas the total glucose‐lowering effect (AUCGIR, 0–t ) 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.