安慰剂对照、随机试验，观察每周一次胰高血糖素样肽-1 受体激动剂度拉鲁肽添加至滴定剂量每日胰岛素甘精的疗效，该研究纳入了 2 型糖尿病患者（AWARD-9）。
Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD-9).
机构信息
Unit of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
Centre of Immunobiology, Barts and the London School of Medicine, Queen Mary University of London, UK.
出版信息
Diabetes Obes Metab. 2017 Jul;19(7):1024-1031. doi: 10.1111/dom.12937. Epub 2017 Apr 10.
AIM
To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimum glycated haemoglobin (HbA1c) concentration.
MATERIALS AND METHODS
Patients (N = 300) from this phase III, double-blind, parallel-arm, placebo-controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks.
RESULTS
Least squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were -1.44 ± 0.09% (-15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and -0.67 ± 0.09% (-7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] -0.77% [-0.97, -0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: -2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%).
CONCLUSIONS
Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.
目的
比较每周给予度拉鲁肽与安慰剂分别联合剂量滴定的甘精胰岛素治疗糖化血红蛋白（HbA1c）控制不佳的 2 型糖尿病（T2D）患者的疗效。
材料和方法
这项 3 期、双盲、平行分组、安慰剂对照研究共纳入 300 例患者，随机给予每周 1.5mg 度拉鲁肽或安慰剂，联合剂量滴定的甘精胰岛素（平均[标准差]基线剂量：39[22]U），联合或不联合二甲双胍（≥1500mg/d）。主要终点为 28 周时，度拉鲁肽/甘精胰岛素治疗组与安慰剂/甘精胰岛素治疗组相比，HbA1c 较基线的变化值是否具有优越性。
结果
最小二乘均数[标准误]HbA1c 自基线的变化值分别为度拉鲁肽/甘精胰岛素组-1.44[0.09]%（-15.74[0.98]mmol/mol）和安慰剂/甘精胰岛素组-0.67[0.09]%（-7.32[0.98]mmol/mol）（28 周时 LS 均数差值[95%置信区间]-0.77%[-0.97，-0.56]；P<0.001）。度拉鲁肽/甘精胰岛素组体重下降，而安慰剂/甘精胰岛素组体重增加（LS 均数差值：-2.41[0.39]kg；P<0.001）。与安慰剂/甘精胰岛素组相比，度拉鲁肽/甘精胰岛素组甘精胰岛素的平均剂量增加幅度显著较小（13[2]U[0.1[0.02]U/kg] vs 26[2]U[0.3[0.02]U/kg]；P<0.001；LS 均数[标准误]最终剂量：度拉鲁肽/甘精胰岛素组 51[2]U，安慰剂/甘精胰岛素组 65[2]U）。低血糖（≤3.9mmol/L 阈值）发生率分别为 7.69[15.15]和 8.56[16.13]事件/患者/年（P=0.488）。度拉鲁肽/甘精胰岛素组发生 1 例严重低血糖事件。度拉鲁肽相关的常见胃肠道不良事件有恶心（12.0%）、腹泻（11.3%）和呕吐（6.0%）。
结论
每周给予 1.5mg 度拉鲁肽联合基础胰岛素治疗是一种有效且耐受良好的治疗选择，适用于 T2D 患者。
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