Duration and onset of action of high dose U‐500 regular insulin in severely insulin resistant subjects with type 2 diabetes

AIM: Although regular human U‐500 insulin (U‐500) is frequently used for insulin resistant type 2 diabetics, pharmacokinetic and pharmacodynamic studies in these individuals are lacking. We set out to determine the rate of onset, duration of action and total glucose lowering effect of two doses of U‐500 insulin in obese insulin resistant subjects with type 2 diabetes. MATERIALS AND METHODS: Randomized double‐blind crossover study was designed to study subjects who were administered either 100 or 200 units SQ of U‐500 insulin once and then were provided intravenous glucose as necessary to maintain euglycaemia. RESULTS: A total of 12 subjects were studied. The time during which intravenous glucose was required to maintain euglycaemia following a 200‐unit dose of U‐500 insulin was significantly greater than the time following a 100‐unit dose. No differences were found between doses in measures related to the rate of onset or in the total amount of intravenous glucose required to maintain euglycaemia for the duration of the study. CONCLUSIONS: The duration of action of U‐500 increases when dose is increased from 100 to 200 units. Neither dose of U‐500 insulin has an onset of action before 2.5 hours after administration. This suggests that U‐500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal and that dosing intervals might need to be extended as dose is increased to avoid hypoglycaemia.