Skolnik Neil, Bonnes Harmony, Yeh Helen, Katz Arie
a Abington Jefferson Health, Family Medicine Residency Program , Jenkintown , PA , USA.
b Family and Community Medicine, Temple University School of Medicine , Philadelphia , PA , USA.
Postgrad Med. 2016 May;128(4):356-63. doi: 10.1080/00325481.2016.1173514. Epub 2016 Apr 18.
To evaluate the efficacy and safety of dapagliflozin 5 and 10 mg/d versus placebo in patients with type 2 diabetes and high baseline A1C defined as A1C ≥ 9% or ≥ 10%.
A post-hoc analysis was conducted of pooled data from 9, 24-week, placebo-controlled clinical studies investigating dapagliflozin as monotherapy, add-on therapy to other oral antidiabetes drugs or insulin, or initial combination therapy with metformin.
At week 24, dapagliflozin 5 and 10 mg/d decreased A1C (≥ 9%: -1.37% and -1.39%, respectively, vs. -0.65% with placebo, both P < 0.0001 and ≥ 10%: -2.13% [P < 0.0001] and -1.59% [P = 0.0003], respectively, vs. -0.82% with placebo), reduced fasting plasma glucose as early as week 1 (P < 0.001 for each dose at all time points for both treatments), and decreased body weight (≥ 9%: P < 0.0001 vs. placebo for both doses; ≥ 10%: P = 0.0065 vs. placebo, 10 mg/d only). Among patients with baseline A1C ≥ 9% who received dapagliflozin 5 or 10 mg/d, 15.7% and 18.9%, respectively, achieved a ≥ 5% decrease in body weight (both P < 0.0001 vs. 3.6% with placebo). Dapagliflozin 10 mg/d decreased systolic and diastolic blood pressure (P < 0.0001 and P = 0.0074 vs. placebo). Adverse events were generally similar across treatment groups, with the exception of a greater frequency of genital infections and hypoglycemia (mostly minor episodes not requiring third-party assistance) in patients receiving dapagliflozin.
In patients with poorly controlled type 2 diabetes defined as A1C ≥ 9% or ≥ 10%, dapagliflozin provided clinically meaningful improvements in glycemic parameters, body weight, and blood pressure, and was generally well tolerated, making it a good therapeutic option for patients with high A1C.
评估达格列净5毫克/天和10毫克/天与安慰剂相比，对基线糖化血红蛋白（A1C）较高（定义为A1C≥9%或≥10%）的2型糖尿病患者的疗效和安全性。
对9项为期24周的安慰剂对照临床研究的汇总数据进行事后分析，这些研究调查了达格列净作为单一疗法、添加到其他口服抗糖尿病药物或胰岛素中，或与二甲双胍联合的初始疗法。
在第24周时，达格列净5毫克/天和10毫克/天降低了糖化血红蛋白（A1C≥9%组：分别为-1.37%和-1.39%，而安慰剂组为-0.65%，两者P<0.0001；A1C≥10%组：分别为-2.13%[P<0.0001]和-1.59%[P=0.0003]，而安慰剂组为-0.82%），早在第1周就降低了空腹血糖（两种治疗在所有时间点的各剂量P<0.001），并减轻了体重（A1C≥9%组：两种剂量与安慰剂相比P<0.0001；A1C≥10%组：仅10毫克/天剂量与安慰剂相比P=0.0065）。在基线A1C≥9%且接受达格列净5毫克/天或10毫克/天治疗的患者中，分别有15.7%和18.9%的人体重减轻≥5%（两者与安慰剂组的3.6%相比P<0.0001）。达格列净10毫克/天降低了收缩压和舒张压（与安慰剂相比P<0.0001和P=0.0074）。各治疗组的不良事件总体相似，但接受达格列净治疗的患者生殖器感染和低血糖（大多为无需第三方协助的轻微发作）的发生率更高。
对于定义为A1C≥9%或≥10%的血糖控制不佳的2型糖尿病患者，达格列净在血糖参数、体重和血压方面带来了具有临床意义的改善，且总体耐受性良好，使其成为高A1C患者的良好治疗选择。
