Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.
Diabetes Obes Metab. 2023 Jan;25(1):89-97. doi: 10.1111/dom.14849. Epub 2022 Sep 8.
To evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro in a paediatric population with type 1 diabetes (T1D) in a Phase 3, treat-to-target study.
After a 4-week lead-in to optimize basal insulin, participants were randomized to double-blind URLi (n = 280) or lispro (n = 298) injected 0 to 2 minutes prior to meals (mealtime), or open-label URLi (n = 138) injected up to 20 minutes after start of meals (postmeal). Participants remained on pre-study basal insulin (degludec, detemir or glargine). The primary endpoint was glycated haemoglobin (HbA1c) change from baseline after 26 weeks (noninferiority margin 4.4 mmol/mol [0.4%]).
Both mealtime and postmeal URLi demonstrated noninferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi -0.23 mmol/mol (95% confidence interval [CI] -1.84, 1.39) and postmeal URLi -0.17 mmol/mol (95% CI -2.15, 1.81). Mealtime URLi reduced 1-hour postprandial glucose (PPG) daily mean (P = 0.001) and premeal to 1 hour postmeal PPG excursion daily mean (P < 0.001) versus lispro. The rate and incidence of severe, nocturnal or documented hypoglycaemia (<3.0 mmol/L [54 mg/dL]) were similar for all treatments. With mealtime URLi versus lispro, the rate of postdose hypoglycaemia (<3.0 mmol/L) was higher at ≤2 hours (P = 0.034). The incidence of treatment-emergent adverse events was similar for all treatments. More participants reported an injection site reaction with mealtime URLi (7.9%) versus postmeal URLi (2.9%) and lispro (2.7%).
In children and adolescents with T1D, URLi demonstrated good glycaemic control, and noninferiority to lispro in HbA1c change for mealtime and postmeal URLi. When dosed at the beginning of meals, URLi reduced 1-hour PPG and PPG excursions versus lispro.
在一项 3 期、以目标为导向的研究中，评估超快速赖脯胰岛素（URLi）与赖脯胰岛素在 1 型糖尿病（T1D）儿科人群中的疗效和安全性。
在优化基础胰岛素的 4 周导入期后，参与者被随机分配至双盲 URLi（n=280）或赖脯胰岛素（n=298）组，分别在餐前 0 至 2 分钟（餐时）或开放标签 URLi（n=138）组接受治疗，在餐前 20 分钟内注射。所有参与者继续使用研究前的基础胰岛素（地特胰岛素、德谷胰岛素或甘精胰岛素）。主要终点是 26 周后与基线相比糖化血红蛋白（HbA1c）的变化（非劣效性边界为 4.4 mmol/mol [0.4%]）。
餐时和餐后 URLi 均显示出与赖脯胰岛素相比对 HbA1c 的非劣效性：餐时 URLi 的估计治疗差异（ETD）为-0.23 mmol/mol（95%置信区间[CI]：-1.84，1.39），餐后 URLi 的 ETD 为-0.17 mmol/mol（95% CI：-2.15，1.81）。与赖脯胰岛素相比，餐时 URLi 降低了餐后 1 小时血糖（PPG）的日均值（P=0.001）和餐前至餐后 1 小时 PPG 漂移的日均值（P<0.001）。所有治疗的严重、夜间或记录的低血糖（<3.0 mmol/L [54 mg/dL]）发生率和发生率均相似。与赖脯胰岛素相比，餐时 URLi 的餐后剂量低血糖（<3.0 mmol/L）发生率在≤2 小时时更高（P=0.034）。所有治疗的治疗中出现的不良事件发生率相似。与餐后 URLi 和赖脯胰岛素相比，更多的参与者报告了餐时 URLi 的注射部位反应（7.9%）。
在 T1D 儿童和青少年中，URLi 显示出良好的血糖控制，并且在餐时和餐后 URLi 对 HbA1c 变化方面显示出与赖脯胰岛素的非劣效性。当在餐前给药时，URLi 降低了餐后 1 小时 PPG 和 PPG 漂移与赖脯胰岛素相比。
Zotero 插件
