Faster Aspart Versus Insulin Aspart as Part of a Basal-Bolus Regimen in Inadequately Controlled Type 2 Diabetes: The onset 2 Trial
Faster Aspart Versus Insulin Aspart as Part of a Basal-Bolus Regimen in Inadequately Controlled Type 2 Diabetes: The onset 2 Trial
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DOI：
10.2337/dc16-1770
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发表时间：
2017-07-01
期刊：
影响因子：
16.2
通讯作者：
Bode, Bruce W.
中科院分区：
文献类型：
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作者：
Bowering, Keith;Case, Christopher;Bode, Bruce W.
本多中心、双盲、达标治疗、3期临床试验评价了速效门冬胰岛素（Faster aspart）与门冬胰岛素（IAsp）在接受基础胰岛素和口服降糖药治疗的2型糖尿病成人患者中的疗效和安全性。研究设计和方法主要终点为治疗26周后HbA（1c）较基线的变化。经过8周导入期优化基础胰岛素后，受试者随机（1：1）接受餐时速效门冬胰岛素（n=345）或IAsp（n =344），使用简单的每日患者驱动算法滴定，加甘精胰岛素U100和二甲双胍。TSHbA（1c）变化为-1.38%（速效门冬胰岛素）和-1.36%（IAsp）;两组的平均HbA（1c）为6.6%。超速效门冬胰岛素在降低HbA（1c）方面表现出非劣效于IAsp（估计治疗差异[ETD] [95% CI] -0.02% [-0.15; 0.10]）。两种治疗均改善了餐后血糖（PPG）控制; 1 h后PPG增量（液体餐试验）具有统计学显著性，有利于速效门冬胰岛素（ETD [95% CI] -0.59 mmol/L [-1.09; -0.09];-10.63 mg/dL [-19.56; -1.69]; P=0.0198），但2-4 h后无统计学显著性。治疗组之间空腹血糖、体重和总体重度/经血糖证实的低血糖发生率（率比[RR] [95% CI] 1.09 [0.88; 1.36]）较基线的变化相似。餐后低血糖（022 h）发生率分别为2.27（速效门冬胰岛素）和1.49（IAsp）/患者-年暴露（RR [95% CI] 1.60 [1.13; 2.27]）。结论在基础-餐时方案中，速效门冬胰岛素和IAsp在HbA（1c）较基线变化方面被证实为非劣效性。超速效门冬胰岛素改善了1小时PPG，与IAsp相比，224小时PPG无差异。除速效门冬胰岛素组022小时餐后低血糖增加外，总体低血糖发生率相似。
OBJECTIVEThis multicenter, double-blind, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in adults with type 2 diabetes receiving basal insulin and oral antidiabetic agents.RESEARCH DESIGN AND METHODSThe primary end point was HbA(1c) change from baseline after 26 weeks' treatment. After an 8-week run-in to optimize basal insulin, subjects were randomized (1:1) to mealtime faster aspart (n=345) or IAsp(n =344), titrated using a simple daily patient-driven algorithm, plus insulin glargine U100 and metformin.RESULTSHbA(1c) change was -1.38% (faster aspart) and -1.36% (IAsp); mean HbA(1c) was 6.6% for both groups. Faster aspart demonstrated noninferiority versus IAsp in reducing HbA(1c) (estimated treatment difference [ETD] [95% CI] -0.02% [-0.15; 0.10]). Both treatments improved postprandial plasma glucose (PPG) control; the PPG increment (liquid meal test) was statistically significant in favor of faster aspart after 1 h (ETD [95% CI] -0.59 mmol/L [-1.09; -0.09]; -10.63mg/dL [-19.56; -1.69]; P=0.0198), but not after 2-4 h. Change from baseline in fasting plasma glucose, body weight, and overall severe/blood glucose-confirmed hypoglycemia rates (rate ratio [RR] [95% CI] 1.09 [0.88; 1.36]) were similar between treatments. Postmeal hypoglycemia (022 h) rates were 2.27 (faster aspart) and 1.49 (IAsp) per patient-year of exposure (RR [95% CI] 1.60 [1.13; 2.27]).CONCLUSIONSFaster aspart and IAsp were confirmed noninferior in a basal-bolus regimen regarding change from baseline in HbA(1c). Faster aspart improved 1-h PPG with no differences in 224-h PPG versus IAsp. Overall hypoglycemia rates were similar except for an increase in 022-h postmeal hypoglycemia with faster aspart.