Eto Takashi, Haranaka Miwa, Kristensen Niels Rode, Navarria Andrea, Nishida Tomoyuki, Ribel-Madsen Rasmus, Søgaard Stinne Byrholdt, Halberg Inge Birk
Hakata Clinic, LTA Medical Co., Fukuoka, Japan.
Novo Nordisk A/S, Søborg, Denmark.
J Diabetes Investig. 2025 Mar;16(3):434-441. doi: 10.1111/jdi.14384. Epub 2024 Dec 12.
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.
胰岛素icodec是一种设计用于每周一次给药的基础胰岛素。本研究评估了icodec在日本1型糖尿病（T1D）患者中的药理学特性。
在一项随机、开放标签、交叉研究中，24名日本T1D患者（20 - 64岁；糖化血红蛋白≤9.0%）接受每周一次的icodec治疗8周，以及每天一次的甘精胰岛素U100治疗14天，每周以个体恒定的等摩尔剂量给药，同时给予门冬胰岛素推注。个体剂量在使用甘精胰岛素U100进行导入期确定，将早餐前自我测量的血浆葡萄糖（SMPG）滴定至4.4 - 7.2 mmol/L。从首次给予icodec剂量直至最后一剂后35天采集用于icodec药代动力学的血样。在最后一剂icodec后24 - 48小时和150 - 168小时以及最后一剂甘精胰岛素U100后0 - 24小时，通过葡萄糖钳夹（目标6.7 mmol/L）测量稳态降糖效果。使用药代动力学/药效学模型模拟icodec的一周降糖效果。在治疗期间从SMPG中识别低血糖情况。
平均在治疗2 - 3周后达到icodec药代动力学稳态。在每周给药间隔期间，模型推导的每日降糖效果分别平均为14.6%、18.0%、16.6%、14.9%、13.3%、11.9%和10.7%。2级低血糖（PG <3.0 mmol/L）发生率在接受icodec治疗的患者中为每患者年暴露37.3次，而接受甘精胰岛素U100治疗的患者为每患者年暴露30.6次。
本研究中icodec在日本T1D患者中的药理学特性支持icodec在日本糖尿病患者中每周一次给药提供基础胰岛素覆盖的潜力。
