Clinical pharmacokinetics · 2026
The Effect of Intrinsic Factors on the Pharmacokinetics of Once-Weekly Insulin Icodec in Type 1 and Type 2 Diabetes: A Population Pharmacokinetic Analysis of Phase II and Phase III trials.
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Kristensen Niels R, Haridas Mundot P, Philis-Tsimikas Athena, Ribel-Madsen Rasmus, Mathieu Chantal
Аннотация
BACKGROUND AND OBJECTIVE: Insulin icodec is a novel basal insulin with pharmacokinetic and pharmacodynamic properties suitable for once-weekly administration. This study evaluated the effect of several intrinsic factors on icodec exposure using population pharmacokinetic modelling.
METHODS: Data for the population pharmacokinetic analysis originated from one phase II and four phase III randomised, parallel-group, treat-to-target clinical trials comparing the efficacy and safety of icodec with once-daily comparators in type 1 or type 2 diabetes. A total of 1244 participants each contributed with up to seven pharmacokinetic samples during 26 weeks of icodec treatment. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to estimate potential effects of individual covariates on apparent clearance.
RESULTS: There were minor or no effects of age, sex, type of diabetes, race, ethnicity, serum albumin level or anti-insulin icodec antibody level on icodec exposure. For all these covariates, the 90% confidence intervals for the icodec exposure ratio versus a reference individual were within the equivalence limits of 0.80-1.25. Icodec exposure was inversely correlated with body weight. However, the effect of body weight was of a magnitude not considered clinically relevant given that icodec, consistent with any other insulin, should be titrated according to individual needs.
CONCLUSIONS: Based on the present pharmacokinetic results, no specific dose recommendations are necessary for icodec across age, sex, type of diabetes, race, ethnicity, body weight, serum albumin level and anti-insulin icodec antibody level.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03751657, NCT04770532, NCT04795531, NCT04880850 and NCT04848480.
METHODS: Data for the population pharmacokinetic analysis originated from one phase II and four phase III randomised, parallel-group, treat-to-target clinical trials comparing the efficacy and safety of icodec with once-daily comparators in type 1 or type 2 diabetes. A total of 1244 participants each contributed with up to seven pharmacokinetic samples during 26 weeks of icodec treatment. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to estimate potential effects of individual covariates on apparent clearance.
RESULTS: There were minor or no effects of age, sex, type of diabetes, race, ethnicity, serum albumin level or anti-insulin icodec antibody level on icodec exposure. For all these covariates, the 90% confidence intervals for the icodec exposure ratio versus a reference individual were within the equivalence limits of 0.80-1.25. Icodec exposure was inversely correlated with body weight. However, the effect of body weight was of a magnitude not considered clinically relevant given that icodec, consistent with any other insulin, should be titrated according to individual needs.
CONCLUSIONS: Based on the present pharmacokinetic results, no specific dose recommendations are necessary for icodec across age, sex, type of diabetes, race, ethnicity, body weight, serum albumin level and anti-insulin icodec antibody level.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03751657, NCT04770532, NCT04795531, NCT04880850 and NCT04848480.