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.
RCT Entities:
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.