Carsten Roepstorff

Steady state is reached within 2–3 days of once‐daily administration of degludec, a basal insulin with an ultralong duration of action

Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim of the present study was to determine time to steady state of insulin degludec (IDeg), a basal insulin analog with an ultralong duration of action, after once‐daily subcutaneous administration in subjects of varying age, diabetes type, and ethnicity.

Pharmacokinetic and pharmacodynamic responses of insulin degludec in African American, white, and Hispanic/Latino patients with type 2 diabetes mellitus.

BACKGROUND Pharmacokinetic and pharmacodynamic profiles of exogenous insulin may be affected by intrinsic factors, such as age, ethnicity/race, and hepatic and renal function. Insulin degludec (IDeg) is a basal insulin with an ultralong duration of action and a flat and stable glucose-lowering effect profile. OBJECTIVE The purpose of this study was to investigate whether the pharmacokinetic and pharmacodynamic responses to IDeg at steady state vary according to patient race/ethnicity. METHODS This randomized, single-center, double-blind, 2-period crossover trial investigated responses to IDeg in 59 patients with type 2 diabetes mellitus from 3 groups: African American, Hispanic/Latino, and white. Patients were allocated randomly to a sequence of 2 treatment periods, separated by a 7- to 21-day washout period, with once-daily IDeg or insulin detemir dosing for 6 days at a predefined fixed dose level (0.6 U/kg). Differences in pharmacokinetic and pharmacodynamic variables among groups were analyzed using an ANOVA with treatment period, an interaction between race/ethnicity, and treatment as fixed factors, subject as a random effect, and residual variance, depending on treatment. RESULTS Total exposure to IDeg during one dosing interval at steady state (AUCIDeg,τ,SS) was similar among the racial/ethnic groups (ratio [95% CI]: African American vs white, 1.10 [0.91-1.31]; African American vs Hispanic/Latino, 1.13 [0.95-1.34]; and Hispanic/Latino vs white, 0.97 [0.82-1.16]). The total glucose-lowering effect of IDeg (AUCGIR,τ,SS) was also similar among the groups, with no statistically significant difference in pairwise comparisons (1940, 1735, and 2286 mg/kg in African American, white, and Hispanic/Latino patients, respectively). Steady state was reached in all groups after 2 to 3 days of dosing. In all groups, both exposure and glucose-lowering effect for IDeg were evenly distributed between the first and second 12 hours of the 24-hour dosing interval at steady state (mean AUCIDeg,0-12h,SS/AUCIDeg,τ,SS = 53%-54%; AUCGIR,0--12h,SS/AUCGIR,τ,SS = 47%-52%). CONCLUSION The similar pharmacokinetic and pharmacodynamic responses to IDeg in 3 racial/ethnic groups of patients with type 2 diabetes mellitus suggest that the flat, stable, and ultralong pharmacokinetic and pharmacodynamic profiles of IDeg are preserved irrespective of race/ethnicity. Although insulin doses must be adjusted on an individual basis, similar pharmacokinetic and pharmacodynamic responses to IDeg are observed in patients with differing race/ethnicity.