在一项随机对照试验（AWARD-11）中，接受二甲双胍治疗的 2 型糖尿病患者使用 3.0mg 和 4.5mg 度拉鲁肽与 1.5mg 度拉鲁肽的疗效和安全性。
Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11).
机构信息
National Research Institute, Los Angeles, CA.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
出版信息
Diabetes Care. 2021 Mar;44(3):765-773. doi: 10.2337/dc20-1473. Epub 2021 Jan 4.
OBJECTIVE
To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin.
RESEARCH DESIGN AND METHODS
Patients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients.
RESULTS
Mean baseline HbA and BMI in randomly assigned patients ( = 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA reductions compared with 1.5 mg (treatment-regimen estimand: -1.77 vs. -1.54% [-19.4 vs. -16.8 mmol/mol], estimated treatment difference [ETD] -0.24% (-2.6 mmol/mol), < 0.001; efficacy estimand: -1.87 vs. -1.53% [-20.4 vs. -16.7 mmol/mol], ETD -0.34% (-3.7 mmol/mol), < 0.001). Dulaglutide 3.0 mg was superior to 1.5 mg for reducing HbA, using the efficacy estimand (ETD -0.17% [-1.9 mmol/mol]; = 0.003) but not the treatment-regimen estimand (ETD -0.10% [-1.1 mmol/mol]; = 0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment regimen: -4.6 vs. -3.0 kg, ETD -1.6 kg, < 0.001; efficacy: -4.7 vs. -3.1 kg, ETD -1.6 kg, < 0.001). Common adverse events through 36 weeks included nausea (1.5 mg, 13.4%; 3 mg, 15.6%; 4.5 mg, 16.4%) and vomiting (1.5 mg, 5.6%; 3 mg, 8.3%; 4.5 mg, 9.3%).
CONCLUSIONS
In patients with type 2 diabetes inadequately controlled by metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA and body weight with a similar safety profile.
目的
比较每周一次给予 3.0 和 4.5mg 剂量的度拉糖肽与 1.5mg 剂量的度拉糖肽治疗未能充分控制的 2 型糖尿病患者的疗效和安全性。
研究设计和方法
患者被随机分配至每周一次接受度拉糖肽 1.5mg、3.0mg 或 4.5mg 治疗 52 周。主要目的是确定度拉糖肽 3.0mg 和（或）4.5mg 在 36 周时降低 HbA1c 的疗效优于 1.5mg。次要优越性目标包括体重变化。两个估计值解决了疗效目标：治疗方案（无论是否停药或使用解救药物）和疗效（无解救药物治疗），所有随机分配的患者均接受治疗。
结果
随机分配患者（n=1842）的基线平均 HbA1c 和 BMI 分别为 8.6%（70mmol/mol）和 34.2kg/m2。在 36 周时，与 1.5mg 相比，4.5mg 度拉糖肽提供了更显著的 HbA1c 降低（治疗方案估计值：-1.77% vs.-1.54%[-19.4 vs.-16.8mmol/mol]，估计治疗差异[ETD]-0.24%[-2.6mmol/mol]，<0.001；疗效估计值：-1.87% vs.-1.53%[-20.4 vs.-16.7mmol/mol]，ETD-0.34%[-3.7mmol/mol]，<0.001）。使用疗效估计值，度拉糖肽 3.0mg 比 1.5mg 更能降低 HbA1c（ETD-0.17%[-1.9mmol/mol]；=0.003），但治疗方案估计值无显著差异（ETD-0.10%[-1.1mmol/mol]；=0.096）。对于 36 周时的体重减轻，4.5mg 度拉糖肽在两种估计值上均优于 1.5mg（治疗方案：-4.6 vs.-3.0kg，ETD-1.6kg，<0.001；疗效：-4.7 vs.-3.1kg，ETD-1.6kg，<0.001）。在 36 周的治疗期间，常见的不良反应包括恶心（1.5mg：13.4%；3mg：15.6%；4.5mg：16.4%）和呕吐（1.5mg：5.6%；3mg：8.3%；4.5mg：9.3%）。
结论
在未能充分控制的 2 型糖尿病患者中，由 1.5mg 度拉糖肽升级至 3.0mg 或 4.5mg 剂量可提供临床相关、剂量依赖性的 HbA1c 和体重降低，安全性相似。
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