Billings Liana K, Asong Marisse, Bøg Martin, Clancy Simon, Kruse Christian, de Laguiche Elisabeth, Maddaloni Ernesto
Department of Medicine, Endeavor Health (Formerly NorthShore University HealthSystem), and University of Chicago Pritzker School of Medicine, 9977 Woods Drive, Suite 300, Skokie, IL, 60077, USA.
Novo Nordisk A/S, Søborg, Denmark.
Diabetes Ther. 2025 Feb;16(2):227-239. doi: 10.1007/s13300-024-01679-3. Epub 2024 Dec 19.
ONWARDS 5 evaluated the effectiveness and safety of insulin icodec (icodec) titrated with a dosing guide app (icodec with app) versus once-daily insulin analogs in insulin-naive adults with type 2 diabetes. The insulin glargine U300 (glargine U300) stratum was too small to enable a robust post hoc efficacy comparison. Augmentation methodology was applied to increase the glargine U300 group size using real-world data (RWD), to facilitate efficacy comparisons of icodec with app versus glargine U300, and to demonstrate the potential of the augmentation methodology to strengthen underpowered treatment comparisons (AUGMENT study).
ONWARDS 5 data were augmented with RWD collected from the US Ambulatory Electronic Medical Records database. Randomized and augmented comparisons (propensity-score-matched) between icodec with app and glargine U300 were weighted to provide a fully augmented estimate of the primary outcome (change in glycated hemoglobin [HbA] after 52 weeks). Data were adjusted for trial effects. Sensitivity analyses were conducted.
The nonaugmented randomized estimated treatment difference (ETD; 95% CI) between icodec with app and glargine U300 (trial stratum) for change in HbA was - 0.21 (- 0.70 to 0.28) percentage points. After adjusting for trial effects, the overall fully augmented ETD (95% CI) was - 0.33 (- 0.68 to 0.01) percentage points numerically in favor of icodec with app, although not statistically significant. Sensitivity analyses supported the findings.
Using augmented data, the precision of the change in HbA estimate was increased compared with the trial stratum analysis alone. These findings help to validate the principle of utilizing augmentation to strengthen trial outcomes.
The ONWARDS 5 trial is registered with ClinicalTrials.gov (NCT04760626).
ONWARDS 5评估了使用剂量指导应用程序滴定的icodec胰岛素（icodec与应用程序联用）与一日一次胰岛素类似物在初治2型糖尿病成年患者中的有效性和安全性。甘精胰岛素U300（甘精胰岛素U300）亚组规模过小，无法进行有力的事后疗效比较。采用增强方法利用真实世界数据（RWD）增加甘精胰岛素U300组的规模，以促进icodec与应用程序联用与甘精胰岛素U300之间的疗效比较，并证明增强方法在加强效能不足的治疗比较方面的潜力（AUGMENT研究）。
ONWARDS 5的数据通过从美国门诊电子病历数据库收集的RWD进行增强。icodec与应用程序联用和甘精胰岛素U300之间的随机和增强比较（倾向得分匹配）进行加权，以提供主要结局（52周后糖化血红蛋白[HbA]变化）的完全增强估计值。数据针对试验效应进行了调整。进行了敏感性分析。
icodec与应用程序联用和甘精胰岛素U300（试验亚组）之间HbA变化的未增强随机估计治疗差异（ETD；95%CI）为-0.21（-0.70至0.28）个百分点。在调整试验效应后，总体完全增强的ETD（95%CI）在数值上为-0.33（-0.68至0.01）个百分点，有利于icodec与应用程序联用，尽管无统计学意义。敏感性分析支持这些发现。
与单独的试验亚组分析相比，使用增强数据提高了HbA变化估计的精度。这些发现有助于验证利用增强来强化试验结果的原则。
ONWARDS 5试验已在ClinicalTrials.gov注册（NCT04760626）。
