Yu Miao, Yuan Guo Yue, Zhang Bin, Wu Hai Ya, Lv Xiao Feng
Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
Department of Endocrinology, Affiliated Hospital of Jiangsu University, Jiangsu, China.
Diabetes Ther. 2020 May;11(5):1147-1159. doi: 10.1007/s13300-020-00804-2. Epub 2020 Apr 10.
To evaluate the efficacy and safety of dulaglutide 0.75 and 1.5 mg in patients with type 2 diabetes mellitus (T2DM) by baseline glycated hemoglobin (HbA1c) < 8.5% or ≥ 8.5% after 26 weeks of treatment.
Assessment of the Weekly AdministRation of dulaglutide in Diabetes (AWARD) China 1 (CHN1) study (NCT01644500, n = 556) included patients on dulaglutide vs. glimepiride who were treatment naïve or on monotherapy but discontinued therapy. AWARD-CHN2 (NCT01648582, n = 591) patients were on dulaglutide vs. insulin glargine and continued on metformin and/or sulfonylurea. Mean daily dose of glimepiride and insulin glargine was 2.51 mg and 21.0 IU, respectively. Post hoc analyses were conducted based on mixed-model repeated measures using a modified intent-to-treat analysis set with only the Chinese population. Change from baseline in HbA1c and body weight was analyzed by individual study.
In the two studies, 70.1% of patients in AWARD-CHN1 and 59.7% in AWARD-CHN2 had baseline HbA1c < 8.5% (mean HbA1c 7.4% and 7.6%, respectively) and 29.9% in AWARD-CHN1 and 40.3% in AWARD-CHN2 had baseline HbA1c ≥ 8.5% (mean HbA1c 9.2% and 9.4%, respectively). In AWARD-CHN1, the HbA1c reductions at 26 weeks with baseline HbA1c < 8.5% and ≥ 8.5%, respectively, were dulaglutide 1.5 mg: - 1.1% and - 2.2%; dulaglutide 0.75 mg: - 0.9% and - 2.0%; glimepiride: - 0.7% and - 1.4%. In AWARD-CHN2, the HbA1c reductions at 26 weeks with baseline HbA1c < 8.5% and ≥ 8.5%, respectively, were dulaglutide 1.5 mg: - 1.2% and - 2.3%; dulaglutide 0.75 mg: - 1.0% and - 1.7%; and insulin glargine: - 0.6% and - 1.7%. Irrespective of baseline HbA1c, body weight decreased with both dulaglutide doses and increased with either glimepiride or insulin glargine at 26 weeks. Dulaglutide demonstrated low incidence of hypoglycemia in both doses in the two trials. Hypoglycemia incidence was generally lower in patients with baseline HbA1c ≥ 8.5%.
Dulaglutide demonstrated significantly greater HbA1c reduction with weight loss and lower risk of hypoglycemia compared with active comparators in Chinese patients with T2DM irrespective of baseline HbA1c, with much greater HbA1c reductions in patients with a higher baseline HbA1c.
ClinicalTrials.gov identifier, NCT01644500 and NCT01648582.
通过治疗26周后糖化血红蛋白（HbA1c）＜8.5%或≥8.5%，评估度拉糖肽0.75mg和1.5mg在2型糖尿病（T2DM）患者中的疗效和安全性。
糖尿病度拉糖肽每周给药评估（AWARD）中国1（CHN1）研究（NCT01644500，n = 556）纳入了接受度拉糖肽与格列美脲治疗的初治患者或接受单药治疗但已停药的患者。AWARD-CHN2（NCT01648582，n = 591）研究中的患者接受度拉糖肽与甘精胰岛素治疗，并继续使用二甲双胍和/或磺脲类药物。格列美脲和甘精胰岛素的平均日剂量分别为2.51mg和21.0IU。采用改良意向性分析集，仅对中国人群进行基于混合模型重复测量的事后分析。通过各独立研究分析HbA1c和体重相对于基线的变化。
在两项研究中，AWARD-CHN1中70.1%的患者和AWARD-CHN2中59.7%的患者基线HbA1c＜8.5%（平均HbA1c分别为7.4%和7.6%），AWARD-CHN1中29.9%的患者和AWARD-CHN2中40.3%的患者基线HbA1c≥8.5%（平均HbA1c分别为9.2%和9.4%）。在AWARD-CHN1中，基线HbA1c＜8.5%和≥8.5%的患者在26周时HbA1c的降低幅度分别为：度拉糖肽1.5mg：-1.1%和-2.2%；度拉糖肽0.75mg：-0.9%和-2.0%；格列美脲：-0.7%和-1.4%。在AWARD-CHN2中，基线HbA1c＜8.5%和≥8.5%的患者在26周时HbA1c的降低幅度分别为：度拉糖肽1.5mg：-1.2%和-2.3%；度拉糖肽0.75mg：-1.0%和-1.7%；甘精胰岛素：-0.6%和-1.7%。无论基线HbA1c如何，两种剂量的度拉糖肽均使体重下降，而格列美脲或甘精胰岛素在26周时使体重增加。在两项试验中，两种剂量的度拉糖肽低血糖发生率均较低。基线HbA1c≥8.5%的患者低血糖发生率总体较低。
在中国T2DM患者中，无论基线HbA1c如何，度拉糖肽与活性对照药相比，HbA1c降低幅度显著更大，伴有体重减轻且低血糖风险更低，基线HbA1c较高的患者HbA1c降低幅度更大。
ClinicalTrials.gov标识符，NCT01644500和NCT01648582。
