Pharmacological characteristics of once-weekly insulin icodec in Japanese individuals with type 1 diabetes.

Abstract

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). 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. 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. 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.