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

Abstract

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.

Insulin aspart has a shorter duration of action than human insulin over a wide dose‐range

“…Our results confirm the faster onset of action and the shorter duration of action of IAsp for a wide dose range observed with lower insulin doses (0.1-0.2 U/kg) in previous studies [5,7,[19][20][21]. Our results confirm the faster onset of action and the shorter duration of action of IAsp for a wide dose range observed with lower insulin doses (0.1-0.2 U/kg) in previous studies [5,7,[19][20][21].…”

“…Rapid-acting insulin analogues such as IAsp have been designed to mimic physiological insulin secretion more closely, thereby leading to lower postprandial blood glucose excursions in DIABETES, OBESITY AND METABOLISM original article comparison with RHI. Our results confirm the faster onset of action and the shorter duration of action of IAsp for a wide dose range observed with lower insulin doses (0.1-0.2 U/kg) in previous studies [5,7,[19][20][21]. This body of evidence suggests that IAsp has significant advantages over RHI in covering prandial insulin requirements even when high doses are used.…”

Comparison of the pharmacokinetics of three concentrations of insulin aspart during continuous subcutaneous insulin infusion (CSII) in a pig model

“…A range of studies have described concentration‐dependent absorption kinetics of subcutaneous bolus injection of human insulin . The different studies concerning human insulin, in different concentrations, showed varying outcomes . Several studies displayed a difference between U40 and U100 human insulin while others failed to do so .…”

“…insulin lispro and insulin aspart) had a faster onset of action and a shorter duration of action compared to both human insulin formulations. Furthermore, the pharmacokinetic and pharmacodynamic profile of human insulin U40 almost overlaps that of human insulin U100, while a more rapid increase for the lower concentration was not confirmed . In contrast, a second study concluded that human insulin U40 was closer to the rapid‐acting analogue than human insulin U100 .…”

“…In contrast to human insulin, the rapid‐acting analogue insulin aspart (IAsp) is primarily in an associated state with dimers and monomers following subcutaneous injection, which gives rise to faster absorption of the analogue . Subcutaneous bolus injection studies have compared human insulin U40 and U100 with rapid‐acting analogues, where the rapid‐acting analogues (i.e. insulin lispro and insulin aspart) had a faster onset of action and a shorter duration of action compared to both human insulin formulations.…”