Gentilella Raffaella, Romera Irene, Nicolay Claudia, Buzzetti Raffaella, Vázquez Luis Alberto, Sesti Giorgio
Eli Lilly Italia, Sesto Fiorentino, Florence, Italy.
Eli Lilly and Company, Alcobendas, Madrid, Spain.
Diabetes Ther. 2019 Jun;10(3):1113-1125. doi: 10.1007/s13300-019-0625-3. Epub 2019 May 4.
This exploratory post hoc analysis investigated the relative changes in glycated haemoglobin (HbA) in patients with type 2 diabetes mellitus (T2DM) treated with dulaglutide versus active comparators across a continuous range of baseline HbA values using data from three phase III randomised controlled trials.
Data from patients receiving once-weekly dulaglutide 0.75 and 1.5 mg, once-daily sitagliptin 100 mg, once-daily liraglutide 1.8 mg or twice-daily exenatide 10 μg in the intent-to-treat populations in the AWARD-5, AWARD-6 and AWARD-1 trials were analysed using last observation carried forward analysis of covariance. Starting with the predefined statistical model from each study, the type of association between HbA baseline and change at 26 weeks was modelled. Consistency of treatment effect was assessed via treatment-by-baseline HbA interaction terms.
Improvements in HbA occurred in all treatment groups across the entire baseline HbA range. The relationship between HbA baseline and magnitude of change was linear in all treatment groups, with greater reductions in patients with higher baseline HbA values. Across the continuum of baseline HbA values, patients treated with dulaglutide 1.5 mg achieved a similar mean HbA reduction to patients receiving liraglutide 1.8 mg and a greater reduction than patients receiving twice-daily exenatide or sitagliptin. In AWARD-5, the treatment-by-baseline HbA interaction P value (0.001) demonstrated progressively greater HbA reduction in dulaglutide-treated compared with sitagliptin-treated patients as baseline HbA increased.
Our results suggest that dulaglutide is an appropriate therapeutic option for patients with T2DM across a wide range of baseline HbA values, including those with poor metabolic control.
Eli Lilly and Company. Plain language summary available for this article.
本探索性事后分析利用三项III期随机对照试验的数据，研究了在连续一系列基线糖化血红蛋白（HbA）值范围内，接受度拉鲁肽治疗的2型糖尿病（T2DM）患者与活性对照药物相比，糖化血红蛋白（HbA）的相对变化情况。
在AWARD - 5、AWARD - 6和AWARD - 1试验的意向性治疗人群中，对接受每周一次度拉鲁肽0.75毫克和1.5毫克、每日一次西格列汀100毫克、每日一次利拉鲁肽1.8毫克或每日两次艾塞那肽10微克治疗的患者数据，采用末次观察结转协方差分析。从每项研究的预定义统计模型开始，对HbA基线与26周时变化之间的关联类型进行建模。通过治疗与基线HbA交互项评估治疗效果的一致性。
在整个基线HbA范围内，所有治疗组的HbA均有改善。所有治疗组中，HbA基线与变化幅度之间的关系呈线性，基线HbA值较高的患者降低幅度更大。在连续的基线HbA值范围内，接受1.5毫克度拉鲁肽治疗的患者平均HbA降低幅度与接受1.8毫克利拉鲁肽治疗的患者相似，且比接受每日两次艾塞那肽或西格列汀治疗的患者降低幅度更大。在AWARD - 5试验中，治疗与基线HbA交互P值（0.001）表明，随着基线HbA升高，与西格列汀治疗的患者相比，度拉鲁肽治疗的患者HbA降低幅度逐渐增大。
我们的结果表明，度拉鲁肽是T2DM患者在广泛的基线HbA值范围内的合适治疗选择，包括代谢控制不佳的患者。
礼来公司。本文提供通俗易懂的摘要。
