Comparison of the time-action profiles of U40- and U100-regular human insulin and the rapid-acting insulin analogue B28 Asp

It is well known that rapid-acting insulin analogues like insulin aspart (B28Asp) show a faster onset and a shorter duration of action than currently available U100 soluble insulin preparations. Since this effect is mainly due to a lower concentration of slow-absorbable hexamers, the metabolic profile of human insulin in lower concentration (e.g. U40 insulin) might be more similar to that of insulin aspart. Therefore, we compared the pharmacodynamic and pharmacokinetic properties of U40 soluble insulin with insulin aspart (U100) and with U100 human insulin. Eight healthy volunteers received on different study days s.c. injection of insulin aspart and U40 insulin (0.2 U/kg body weight) under euglycaemic clamp conditions (blood glucose 5 mmol/l, basal i.v. insulin infusion 0.15 mU/kg/min). In a second study, U40 and U100 soluble insulin was administered to 9 other volunteers under similar conditions. No significant differences were observed between the summary measures of U40 and U100 insulin. Insulin aspart showed a faster onset and a shorter duration of action than U40 insulin. The metabolic activity of human insulin in concentrations of U40 and U100 is comparable. Subcutaneous injection of the insulin analogue insulin aspart leads to a faster onset and a shorter duration of action even in comparison to U40 insulin.