A novel insulin formulation with a more rapid onset of action

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.