Physicians East, PA, Greenville, North Carolina, USA.
Atlanta Diabetes Associates, Atlanta, Georgia, USA.
Diabetes Obes Metab. 2021 Jul;23(7):1552-1561. doi: 10.1111/dom.14368. Epub 2021 Mar 23.
To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro (Humalog ) in people with type 1 diabetes on continuous subcutaneous insulin infusion (CSII).
This was a phase 3, 16-week, treat-to-target study in patients randomized to double-blind URLi (N = 215) or lispro (N = 217). The primary endpoint was change from baseline HbA1c (non-inferiority margin 4.4 mmol/mol [0.4%]), with multiplicity-adjusted objectives for postprandial glucose (PPG) levels during a meal test, and time spent in the target range 70-180 mg/dL (TIR).
URLi was non-inferior to lispro for change in HbA1c, with a least-squares mean (LSM) difference of 0.3 mmol/mol (95% confidence interval [CI] -0.6, 1.2) or 0.02% (95% CI -0.06, 0.11). URLi was superior to lispro in controlling 1- and 2-h PPG levels after the meal test: LSM difference -1.34 mmol/L (95% CI -2.00, -0.68) or -24.1 mg/dL (95% CI -36.0, -12.2) at 1 h and -1.54 mmol/L (95% CI -2.37, -0.72) or -27.8 mg/dL (95% CI -42.6, -13.0) at 2 h; both p < .001. TIR and time in hyperglycaemia were similar between groups but URLi resulted in significantly less time in hypoglycaemia (<3.0 mmol/L [54 mg/dL]) over the daytime, night-time and 24-h period: LSM difference -0.41%, -0.97% and -0.52%, respectively, all p < .05. The incidence of treatment-emergent adverse events was higher with URLi (60.5% vs. 44.7%), driven by infusion-site reaction and infusion-site pain, which was mostly mild or moderate. Rates of severe hypoglycaemia and diabetic ketoacidosis were similar between groups.
URLi was efficacious, providing superior PPG control and less time in hypoglycaemia but with more frequent infusion-site reactions compared with lispro when administered by CSII.
评估超短效赖脯胰岛素（URLi）与赖脯胰岛素（Humalog）在接受连续皮下胰岛素输注（CSII）的 1 型糖尿病患者中的疗效和安全性。
这是一项为期 16 周、以目标为导向的 3 期研究，患者随机分为双盲 URLi（N=215）或赖脯胰岛素（N=217）组。主要终点是从基线 HbA1c（非劣效性边界 4.4mmol/mol[0.4%]）的变化，以及餐时试验中餐后血糖（PPG）水平和 70-180mg/dL（TIR）目标范围内时间的多重调整目标。
与赖脯胰岛素相比，URLi 在 HbA1c 方面无差异，最小二乘均值（LSM）差值为 0.3mmol/mol（95%置信区间[CI] -0.6，1.2）或 0.02%（95% CI -0.06，0.11）。与赖脯胰岛素相比，URLi 在控制餐后试验 1 小时和 2 小时的 PPG 水平方面具有优势：LSM 差值分别为-1.34mmol/L（95% CI -2.00，-0.68）或-24.1mg/dL（95% CI -36.0，-12.2）和-1.54mmol/L（95% CI -2.37，-0.72）或-27.8mg/dL（95% CI -42.6，-13.0）；均p<0.001。两组间 TIR 和高血糖时间相似，但 URLi 导致白天、夜间和 24 小时期间的低血糖时间明显减少：LSM 差值分别为-0.41%、-0.97%和-0.52%，均p<0.05。与赖脯胰岛素相比，URLi 治疗期间不良事件的发生率更高（60.5% vs. 44.7%），主要由输注部位反应和输注部位疼痛引起，这些反应大多为轻度或中度。两组间严重低血糖和糖尿病酮症酸中毒的发生率相似。
与赖脯胰岛素相比，URLi 能有效控制 PPG，减少低血糖时间，但与赖脯胰岛素相比，CSII 给药时，URLi 导致输注部位反应和输注部位疼痛的频率更高。
