Impact of setting distinct target blood glucose levels on endogenous insulin suppression and pharmacodynamics of insulin preparations.

backgroundInsulin therapy plays a crucial role in managing diabetes. Regulatory guidelines mandate assessing the pharmacokinetics (PK) and pharmacodynamics (PD) of new insulin formulations with euglycemic clamp techniques before entry into the market. Typically, blood glucose (BG) levels are maintained at 5% below baseline to suppress endogenous insulin secretion in healthy volunteers. However, in scenarios where BG baseline is relatively low, maintaining it at 5% below baseline can increase hypoglycemic risk. Consequently, we adjusted to maintain it at 2.5% below a baseline of < 4.00 mmol/L. It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.

aimTo evaluate and compare the PD and C-peptide status using two different target BG setting methods.

methodsData came from euglycemic clamp trials assessing the PK/PD of insulin aspart (IAsp) in healthy participants. Target BG was set at 2.5% below baseline for those with a basal BG of < 4.00 mmol/L (group A), and at 5% below baseline for others (group B). The area under the curve (AUC) of IAsp (AUC

resultsOut of 135 subjects, 15 were assigned to group A and 120 to group B; however, group B exhibited higher basal C-peptide (1.59 ± 0.36

conclusionMaintaining BG at 2.5% below a baseline of < 4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.