Regular human insulin (RHI) at high doses shows prolongation of its duration of action potentially leading to late postprandial hypoglycaemia. This study compared late metabolic activity (4–12 and 6–12 h post-dosing) and duration of action (time to reach late half-maximal activity) over a range of doses between insulin aspart (IAsp) and RHI.Methods:
Pharmacokinetic and pharmacodynamic properties of subcutaneous IAsp and RHI (6, 12 and 24 (I)U) were compared in 16 healthy subjects in this double-blind, randomized, six-way crossover glucose clamp study.Results:
With increasing doses of both insulins, metabolic activity, insulin exposure, maximum metabolic effect and maximum serum insulin concentration increased linearly. Late metabolic activity was lower for IAsp than RHI at all doses, reaching statistical significance (p < 0.05) for 12 and 24 (I)U. Likewise, IAsp had a shorter duration of action at all doses (p < 0.01) and reached time to 80% of total metabolic activity earlier at doses of 12 and 24 (I)U (p < 0.05). IAsp, compared with RHI, showed a higher maximum metabolic effect at 12 and 24 (I)U (p < 0.0001) and a stronger early metabolic activity for all three doses (p < 0.05).Conclusions:
IAsp showed a shorter duration of action and, particularly with doses of 12 and 24 (I)U, less late metabolic activity than RHI. These properties might contribute to the lower incidence of hypoglycaemia observed with IAsp versus RHI in clinical trials as lower late metabolic activity should decrease the risk of late postprandial hypoglycaemia.