Effect of physicochemical variables of regular insulin formulations on their absorption from the subcutaneous tissue

Abstract

Background: Physicochemical properties of regular insulin formulations influence the subcutaneous absorption kinetics. Aim of study: To compare the subcutaneous absorption of regular insulin formulations with different concentration, temperature and hexamer-aggregation. Study design: In random order, 24 fasting healthy men were injected with identical doses of regular human insulin in concentrations of 40 units/ml (U40), 100 units/ml (U100), and the insulin analogue Lispro; regular human insulin U100 was applied at either 8, or 37°C. Insulinaemia, C-peptide and plasma glucose levels were monitored for every 15 min up to 45 min after the injection. Results: In comparison to U100 human regular insulin, Lispro induced significantly higher insulinaemia 15–45 min after injection. In comparison to U40 insulin, however, insulinaemia was higher only at 15 and 30 min after injection, and was comparable at 45 min (210±11 pmol/l after Lispro versus 191±15 pmol/l after U40 regular insulin; P>0.06). There was no difference in insulinaemia between U100 regular insulin of 8 or 37°C. C-peptide and plasma glucose levels were altered accordingly. Conclusion: Assuming identical clearance rates of human insulin and Lispro, our data show that insulin absorption is substantially increased by reduced hexamer-aggregation (e.g. with insulin analogue Lispro), when compared to U100 regular human insulin. It is only marginally better, when compared to U40 regular human insulin. The increase in insulin temperature from 8 to 37°C had no effect on the respective absorption kinetics.