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

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. 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. 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. 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. ClinicalTrials.gov identifiers: NCT03751657, NCT04770532, NCT04795531, NCT04880850 and NCT04848480.