Profil, Neuss, Germany.
Novo Nordisk, Søborg, Denmark.
Diabetes Obes Metab. 2024 May;26(5):1941-1949. doi: 10.1111/dom.15510. Epub 2024 Feb 20.
To investigate the pharmacokinetic/pharmacodynamic properties of once-weekly insulin icodec in individuals with type 1 diabetes (T1D).
In this randomized, open-label, two-period crossover trial, 66 individuals with T1D (age 18-64 years; glycated haemoglobin ≤75 mmol/mol [≤ 9%]) were to receive once-weekly icodec (8 weeks) and once-daily insulin glargine U100 (2 weeks) at individualized fixed equimolar total weekly doses established during up to 10 weeks' run-in with glargine U100 titrated to pre-breakfast plasma glucose (PG) of 4.4-7.2 mmol/L (80-130 mg/dL). Insulin aspart was used as bolus insulin. Blood sampling for icodec pharmacokinetics was performed from the first icodec dose until 35 days after the last dose. The glucose infusion rate at steady state was assessed in glucose clamps (target 6.7 mmol/L [120 mg/dL]) at 16-52 h and 138-168 h after the last icodec dose and 0-24 h after the last glargine U100 dose. Icodec pharmacodynamics during 1 week were predicted by pharmacokinetic-pharmacodynamic modelling. Hypoglycaemia was recorded during the treatment periods based on self-measured PG.
Icodec reached pharmacokinetic steady state on average within 2-3 weeks. At steady state, model-predicted daily proportions of glucose infusion rate during the 1-week dosing interval were 14.3%, 19.6%, 18.3%, 15.7%, 13.1%, 10.6% and 8.4%, respectively. Rates and duration of Level 2 hypoglycaemic episodes (PG <3.0 mmol/L [54 mg/dL]) were 32.8 versus 23.9 episodes per participant-year of exposure and 33 ± 25 versus 30 ± 18 min (mean ± SD) for icodec versus glargine U100.
The pharmacokinetic/pharmacodynamic properties of icodec suggest its potential to provide basal coverage in a basal-bolus insulin regimen in people with T1D.
研究 1 型糖尿病（T1D）患者每周一次胰岛素icodec 的药代动力学/药效学特性。
在这项随机、开放标签、两周期交叉试验中，66 名 T1D 患者（年龄 18-64 岁；糖化血红蛋白≤75mmol/mol[≤9%]）将接受每周一次 icodec（8 周）和每日一次甘精胰岛素 U100（2 周）治疗，剂量为个体化固定等摩尔总每周剂量，在长达 10 周的甘精胰岛素 U100 滴定至早餐前血浆葡萄糖（PG）4.4-7.2mmol/L（80-130mg/dL）期间确定。胰岛素门冬氨酸用作餐时胰岛素。从第一次 icodec 剂量开始至最后一次剂量后 35 天进行 icodec 药代动力学采样。最后一次 icodec 剂量后 16-52 小时和 138-168 小时以及最后一次甘精胰岛素 U100 剂量后 0-24 小时，在葡萄糖钳夹中评估稳态时的葡萄糖输注率（目标 6.7mmol/L[120mg/dL]）。在治疗期间根据自我测量的 PG 记录低血糖事件。
icodec 平均在 2-3 周内达到药代动力学稳态。在稳态时，模型预测的 1 周给药间隔内葡萄糖输注率的日比例分别为 14.3%、19.6%、18.3%、15.7%、13.1%、10.6%和 8.4%。低血糖(Level 2)发作的发生率和持续时间（PG<3.0mmol/L[54mg/dL]）分别为每参与者年 32.8 次和 23.9 次，icodec 与甘精胰岛素 U100 相比分别为 33±25 分钟和 30±18 分钟（均值±标准差）。
icodec 的药代动力学/药效学特性表明，它有可能在 T1D 患者的基础-餐时胰岛素治疗方案中提供基础覆盖。
