INTRODUCTION: Insulin icodec is a basal insulin designed for once-weekly administration. This study assessed the pharmacological properties of icodec in Japanese individuals with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized, open-label, crossover study, 24 Japanese individuals with T1D (20-64 years
glycated hemoglobin ≤9.0%) received once-weekly icodec for 8 weeks and once-daily insulin glargine U100 for 14 days at individual constant equimolar doses per week together with bolus insulin aspart. Individual doses were determined during run-in with glargine U100 titrated to prebreakfast self-measured plasma glucose (SMPG) of 4.4-7.2 mmol/L. Blood samples for icodec pharmacokinetics were taken from the first icodec dose until 35 days after last dose. The steady-state glucose-lowering effect was measured in glucose clamps (target 6.7 mmol/L) during 24-48 h and 150-168 h after last icodec dose and 0-24 h after last glargine U100 dose. One-week glucose-lowering effect of icodec was simulated using a pharmacokinetic/pharmacodynamic model. Hypoglycemia was identified from SMPG during the treatment periods. RESULTS: Icodec pharmacokinetic steady state was achieved on average after 2-3 weeks of treatment. Model-derived daily glucose-lowering effect during the weekly dosing interval averaged 14.6%, 18.0%, 16.6%, 14.9%, 13.3%, 11.9%, and 10.7%, respectively. Rates of level 2 hypoglycemia (PG <
3.0 mmol/L) were 37.3 vs 30.6 episodes per patient-year of exposure for icodec vs glargine U100. DISCUSSION: Icodec pharmacological properties in Japanese individuals with T1D in this study support the potential of icodec to provide basal insulin coverage with once-weekly dosing in Japanese individuals with diabetes.