A novel insulin formulation with a more rapid onset of action

Abstract

Aims/hypothesis: This study evaluates the pharmacodynamic and pharmacokinetic properties of the novel ultra-fast insulin product VIAject, a formulation of human soluble insulin and generally recognised as safe ingredients designed to increase the rate of absorption.

Methods: We performed five euglycaemic glucose clamps (Biostator; target blood glucose 5 mmol/l) in ten healthy volunteers. Using a crossover design with a fixed treatment order, 12 IU human soluble insulin, 12 U insulin lispro and 12 IU ultra-fast insulin were injected s.c. in the abdominal region on three study days. On the other two study days, 6 and 3 IU ultra-fast insulin were injected.

Results: Subcutaneous injection of 12 IU ultra-fast insulin resulted in a time-action profile characterised by an even more rapid onset of action and maximal metabolic activity than insulin lispro: time to early half-maximal activity was 33 +/- 17 min (mean +/- SD) vs insulin lispro 51 +/- 13 min vs human soluble insulin 66 +/- 15 min (p < 0.05 ultra-fast insulin<insulin lispro<human soluble insulin); time to maximal activity was 136 +/- 56 min vs insulin lispro 152 +/- 30 min vs human soluble insulin 193 +/- 57 min (p < 0.05 ultra-fast insulin and insulin lispro<human soluble insulin). The metabolic activity in the first 2 h after injection was higher with ultra-fast insulin and insulin lispro than with human soluble insulin (AUC glucose infusion rate [GIR] 0-120 min: 915 +/- 301 and 781 +/- 174 vs 580 +/- 164 mg/kg; p < 0.05). A clear dose-response relationship was observed with the three doses of ultra-fast insulin: AUCGIR 0-120 min 12 IU 915 +/- 301 vs 6 IU 718 +/- 255 vs 3 IU 524 +/- 262 mg/kg (p < 0.05). The pharmacokinetic data confirmed the pharmacodynamic results.

Conclusions/interpretation: This study shows that the onset of action of VIAject is faster than that of human soluble insulin and insulin lispro.

Fig. 1

Mean serum insulin profiles (a), normalised mean serum insulin levels (b) and GIR profiles (c) after baseline correction obtained after s.c. application of 12 IU human soluble insulin (dotted lines), 12 U insulin lispro (bold lines) and 12 IU ultra-fast insulin (non-bold lines) in ten healthy participants. (b) For normalisation of the mean serum insulin levels the maximal serum insulin value observed after s.c. injection with each of the three insulin formulations was set as 100% and all other values were calculated as a proportion of these. The dose–response relationship of the observed mean serum insulin levels (d) and GIRs (e) with two additional doses of ultra-fast insulin (6 IU, dashed lines; 3 IU, dotted lines) were also studied. To convert GIR in mg kg^–1 min^–1 to μmol kg^–1 min^–1 multiply by 5.5