How to Accurately Establish Pharmacokinetics/Pharmacodynamics of Long-Acting Insulins in Humans: Relevance to Biosimilar Insulins

PK and PD of insulin NPH and insulin IGlar in normal volunteers at a dose of 0.4 units/kg (left panel) (20) and in T1D subjects at a dose of 0.3 units/kg (right panel) (5). In both studies, glucose was infused to maintain plasma glucose at the target euglycemia in normal volunteers and at 130 mg/dL in T1D subjects. In the second 12 h of the studies (time 12–24 h) in T1D subjects treated with NPH, plasma insulin concentration fell below that of IGlar and the insulin deficiency resulted in lower glucose infusion rate and earlier and greater hyperglycemia as compared with IGlar (right panel). In contrast, in normal volunteers, in the same time interval of 12–24 h, plasma insulin concentrations, glucose infusion rate, and plasma glucose concentrations with NPH and IGlar did not differ (left panel). Thus, the ongoing endogenous insulin secretion of normal volunteers masked the different PK/PD of NPH and IGlar seen in T1D. Figure made after data were extrapolated from the original figures of Heinemann et al. (20) and Lepore et al. (5).