与优泌乐相比，超快速赖脯胰岛素在日本1型糖尿病患者中的疗效和安全性：PRONTO-T1D亚组分析
Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog in Japanese Patients with Type 1 Diabetes: PRONTO-T1D Subpopulation Analysis.
作者信息
Miura Junnosuke, Imori Makoto, Nishiyama Hiroshi, Imaoka Takeshi
机构信息
Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., 5-1-28, Isogami-dori, Chuo-ku, Kobe, Hyogo, 651-0086, Japan.
出版信息
Diabetes Ther. 2020 Sep;11(9):2089-2104. doi: 10.1007/s13300-020-00892-0. Epub 2020 Jul 29.
INTRODUCTION
We evaluated the efficacy and safety of ultra-rapid lispro (URLi) in comparison to lispro in a subgroup analysis of Japanese adults with type 1 diabetes mellitus from the phase 3 PRONTO-T1D trial.
METHODS
After an 8-week lead-in to optimize basal insulin treatment, patients were randomized to 52-week double-blind mealtime URLi or lispro, or 26-week open-label postmeal URLi. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline (week 0) to week 26 between mealtime URLi and lispro. The multiplicity adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a meal test between mealtime URLi and lispro, and change in HbA1c from baseline to week 26 between postmeal URLi and mealtime lispro.
RESULTS
This manuscript presents pre-specified exploratory analyses of 26-week data from Japanese patients randomized to double-blind URLi (n = 62) or lispro (n = 59), or open-label URLi (n = 46). Mean baseline HbA1c levels were 7.52% for mealtime URLi, 7.44% for lispro, and 7.51% for postmeal URLi at randomization. At week 26, the least squares mean (LSM) difference compared to lispro was 0.04% (95% confidence interval [CI] - 0.14 to 0.22) for mealtime URLi, and 0.16% (95% CI - 0.04 to 0.35) for postmeal URLi. In comparison to lispro, mealtime URLi resulted in statistically significantly lower 1- and 2-h PPG excursions during the mixed-meal tolerance test. LSM differences were - 40.5 mg/dL, 95% CI - 59.5 to 21.4 (- 2.25 mmol/L, 95% CI - 3.3 to - 1.2) for 1-h PPG excursions and - 51.7 mg/dL, 95% CI - 81.7 to - 21.8 (- 2.87 mmol/L, 95% CI - 4.5 to - 1.2) for 2-h PPG excursions at week 26. There were no significant treatment differences in rates of severe/overall hypoglycemia, or incidence of treatment-emergent adverse events.
CONCLUSIONS
Mealtime and postmeal URLi provide effective and comparable glycemic control in Japanese patients. Mealtime URLi demonstrated more effective PPG control compared to lispro.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03214367.
引言
在3期PRONTO-T1D试验的日本1型糖尿病成年患者亚组分析中，我们比较了超快速赖脯胰岛素（URLi）与赖脯胰岛素的疗效和安全性。
方法
在进行为期8周的导入期以优化基础胰岛素治疗后，患者被随机分为接受52周双盲餐时URLi或赖脯胰岛素治疗，或26周开放标签餐后URLi治疗。主要终点是餐时URLi与赖脯胰岛素治疗组从基线（第0周）到第26周糖化血红蛋白（HbA1c）的变化。多重性调整后的目标是餐时URLi与赖脯胰岛素治疗组在餐后试验后的1小时和2小时餐后血糖（PPG）波动，以及餐后URLi与餐时赖脯胰岛素治疗组从基线到第26周HbA1c的变化。
结果
本手稿展示了对随机分配至双盲URLi组（n = 62）、赖脯胰岛素组（n = 59）或开放标签URLi组（n = 46）的日本患者26周数据进行的预先指定的探索性分析。随机分组时，餐时URLi组的平均基线HbA1c水平为7.52%，赖脯胰岛素组为7.44%，餐后URLi组为7.51%。在第26周时，餐时URLi组与赖脯胰岛素组相比，最小二乘均值（LSM）差异为0.04%（95%置信区间[CI] -0.14至0.22），餐后URLi组与餐时赖脯胰岛素组相比为0.16%（95% CI -0.04至0.35）。与赖脯胰岛素相比，餐时URLi在混合餐耐量试验期间导致1小时和2小时PPG波动在统计学上显著更低。第26周时，1小时PPG波动的LSM差异为-40.5 mg/dL，95% CI -59.5至21.4（-2.25 mmol/L，95% CI -3.3至-1.2）；2小时PPG波动的LSM差异为-51.7 mg/dL，95% CI -81.7至-21.8（-2.87 mmol/L，95% CI -4.5至-1.2）。在严重/总体低血糖发生率或治疗中出现的不良事件发生率方面，治疗差异无统计学意义。
结论
餐时和餐后URLi在日本患者中提供了有效且相当的血糖控制。与赖脯胰岛素相比，餐时URLi在PPG控制方面更有效。
试验注册
ClinicalTrials.gov，NCT03214367。
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