Aim: to compare pharmacokinetic (PK) and pharmacodynamic (PD) properties of faster-acting insulin aspart (faster aspart) with those of insulin aspart (IAsp) at three clinically relevant doses in adults with type 1 diabetes (T1D).

Materials and methods: 46 subjects (44.0±10.4 years) received a single dose (0.1, 0.2 or 0.4 U/kg) of faster aspart or IAsp in a randomised, double-blind, crossover sequence. PK/PD properties were evaluated using a euglycaemic clamp (blood glucose [BG] target 5.5 mmol/l; duration 12 h post-dose).

Results: onset of appearance with faster aspart occurred approximately twice as fast (mean [95% CI] and relative difference for 0.1 U/kg: −4.7 min [−6.0;−3.4] and 47%; 0.2 U/kg: −4.7 min [−5.4;−4.0] and 54%; 0.4 U/kg: −4.1 min [−5.3;−3.0] and 56%) (Table) vs. IAsp. T50%C_max was earlier (8–12 min; 24–32%) with faster aspart vs. IAsp. Insulin exposure was up to twofold higher in the first 30 min with faster aspart vs. IAsp. For both faster aspart and IAsp, total exposure and C_max increased with increasing dose. Onset of action occurred up to 26% faster with faster aspart (mean [95% CI] and relative difference for 0.1 U/kg: −5.0 min [−10.0;−0.0] and 20%; 0.2 U/kg: −5.8 min [−8.6;−3.1] and 26%; 0.4 U/kg: −5.6 min [−8.8;−2.4] and 26%) vs. IAsp. T50%GIR_max occurred earlier (9–12 min; 22–25%) with faster aspart vs. IAsp. Faster aspart’s early glucose-lowering effect was up to twofold greater within the first 30 min vs. IAsp, while total and maximum glucose-lowering effects were similar. Both treatments were well tolerated and had no safety issues; no injection-site reactions were observed.

Conclusion: Faster aspart produced a faster onset of exposure and a greater initial absorption, associated with greater early action, than IAsp across all three doses.