超快速赖脯胰岛素（URLi）在1型糖尿病成人患者中的长期疗效和安全性：PRONTO-T1D扩展研究
Long-Term Efficacy and Safety of Ultra Rapid Lispro (URLi) in Adults with Type 1 Diabetes: The PRONTO-T1D Extension.
作者信息
Bue-Valleskey Juliana, Klaff Leslie, Cho Jang Ik, Dellva Mary Anne, Schloot Nanette C, Tobian Janet, Miura Junnosuke, Dahl Dominik
机构信息
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
Rainier Clinical Research Center, Renton, WA, USA.
出版信息
Diabetes Ther. 2021 Feb;12(2):569-580. doi: 10.1007/s13300-020-00987-8. Epub 2021 Jan 17.
INTRODUCTION
The PRONTO-T1D study, which evaluated the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes (T1D), met the primary endpoint of noninferiority of HbA1c change from baseline compared to lispro at 26 weeks. We present results of an additional 26-week treatment phase evaluating long-term efficacy and safety of URLi.
METHODS
In this phase 3, treat-to-target study, subjects were randomized to double-blind mealtime URLi, lispro, or open-label postmeal URLi with insulin degludec or glargine for 26 weeks. Subjects in the double-blind URLi (n = 451) and lispro (n = 442) groups continued for another 26 weeks to assess long-term efficacy and safety.
RESULTS
HbA1c increased marginally during the long-term maintenance period (week 26-52) in both groups to 7.47% (URLi) and 7.54% (lispro). At week 52, there were no statistically significant treatment differences in change from baseline HbA1c with a least-squares mean treatment difference (95% confidence interval) of - 0.06% (- 0.16, 0.03). Proportions of patients with HbA < 7% at week 52 were similar (URLi, 26.8%; lispro, 24.5%). Self-monitored blood glucose (SMBG) showed that 1-h (9.23 versus 10.14 mmol/L) and 2-h (8.40 versus 9.53 mmol/L) postmeal daily mean glucose was statistically significantly (p < 0.001) lower with URLi than lispro. The rate and incidence of severe, documented, and postprandial hypoglycemia (< 54 mg/dl [3.0 mmol/L]) were similar between treatments, but URLi demonstrated a 31% lower rate in the period more than 4 h after meals, (p = 0.023). Injection site reactions were reported by 3.3% of patients on URLi and 0.9% on lispro. The incidence of treatment-emergent adverse events was similar between treatments.
CONCLUSION
Overall glycemic control and improved postprandial glucose via SMBG were maintained after 52 weeks with URLi versus lispro, suggesting that the efficacy of URLi is preserved during long-term treatment in patients with T1D. No long-term safety issues were identified with URLi.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03214367.
引言
PRONTO-T1D研究评估了超快速赖脯胰岛素（URLi）与赖脯胰岛素在1型糖尿病（T1D）成人患者中的疗效和安全性，该研究达到了26周时HbA1c自基线变化非劣于赖脯胰岛素的主要终点。我们展示了另外一个26周治疗阶段评估URLi长期疗效和安全性的结果。
方法
在这项3期达标治疗研究中，受试者被随机分为双盲餐时URLi组、赖脯胰岛素组，或与德谷胰岛素或甘精胰岛素联用的开放标签餐后URLi组，治疗26周。双盲URLi组（n = 451）和赖脯胰岛素组（n = 442）的受试者继续治疗另外26周，以评估长期疗效和安全性。
结果
两组在长期维持期（第26 - 52周）HbA1c均略有升高，分别为7.47%（URLi）和7.54%（赖脯胰岛素）。在第52周时，与基线HbA1c变化的治疗差异无统计学意义，最小二乘均数治疗差异（95%置信区间）为 - 0.06%（- 0.16，0.03）。第52周时HbA＜7%的患者比例相似（URLi为26.8%；赖脯胰岛素为24.5%）。自我监测血糖（SMBG）显示，URLi组餐后1小时（9.23对10.14 mmol/L）和2小时（8.40对9.53 mmol/L）的每日平均血糖在统计学上显著低于赖脯胰岛素组（p＜0.001）。严重、有记录的餐后低血糖（＜54 mg/dl [3.0 mmol/L]）的发生率和频率在各治疗组间相似，但URLi组在餐后超过4小时的时间段内发生率低31%（p = 0.023）。使用URLi的患者中有3.3%报告了注射部位反应，使用赖脯胰岛素的患者中这一比例为0.9%。治疗中出现的不良事件发生率在各治疗组间相似。
结论
与赖脯胰岛素相比，URLi治疗52周后总体血糖控制良好，通过SMBG显示餐后血糖得到改善，这表明URLi在T1D患者长期治疗期间疗效得以维持。未发现URLi存在长期安全性问题。
试验注册
ClinicalTrials.gov，NCT03214367。
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