Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes
Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes
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DOI：
10.2337/dc08-1863
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发表时间：
2009-04-01
期刊：
影响因子：
16.2
通讯作者：
Fiedorek, Fred T.
中科院分区：
文献类型：
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作者：
List, James F.;Woo, Vincent;Fiedorek, Fred T.
目的-达格列净，一种新的肾脏钠-葡萄糖协同转运蛋白2抑制剂，允许一种非胰岛素依赖的方法来改善2型糖尿病高血糖。在这个多剂量研究中，我们评估了达格列净在2型糖尿病patients.RESEARCH设计和方法的安全性和有效性-2型糖尿病患者被随机分配到一个五达格列净剂量，二甲双胍XR，或安慰剂12周。主要目的是比较A1 C较基线的平均变化。其他目的包括比较空腹血糖（FPG）、体重、不良事件和实验室测量值的变化。结果-12周后，达格列净诱导中度糖尿（52-85 g尿糖/天），并与安慰剂相比显示出显著的血糖改善（Δ A1 C-0.55至-0.90%和Δ FPG-16至-31 mg/dl）。与安慰剂相比的体重减轻变化为-1.3至-2.0 kg。肾功能无变化。在较高剂量下，血清尿酸降低，血清镁升高，血清磷酸盐升高，剂量相关的24小时尿量和红细胞压积升高，所有这些都是小幅度的。治疗后出现的不良事件在所有groups.CONCLUSIONS相似-达格列净改善高血糖症和促进体重减轻2型糖尿病患者通过诱导控制糖尿与尿损失类似200-300千卡/天，达格列净治疗没有表现出持久的，临床上显着的渗透压体积，或肾脏状态的变化。
OBJECTIVE - Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients.RESEARCH DESIGN AND METHODS - Type 2 diabetic patients were randomly assigned to one of five dapagliflozin doses, metformin XR, or placebo for 12 weeks. The primary objective was to compare mean change from baseline in A1C. Other objectives included comparison of changes in fasting plasma glucose (FPG), weight, adverse events, and laboratory measurements.RESULTS - After 12 weeks, dapagliflozin induced moderate glucosuria (52-85 g urinary glucose/day) and demonstrated significant glycemic improvements versus placebo (Delta A1C -0.55 to -0.90% and Delta FPG -16 to -31 mg/dl). Weight loss change versus placebo was -1.3 to -2.0 kg. There was no change in renal function. Serum uric acid decreased, serum magnesium increased, serum phosphate increased at higher doses, and dose-realated 24-h urine volume and hematocrit increased, all of small magnitude. Treatment-emergent adverse events were similar across all groups.CONCLUSIONS - Dapagliflozin improved hyperglycemia and facilitates weight loss in type 2 diabetic patients by inducing controlled glucosuria with urinary loss of similar to 200-300 kcal/day, Dapagliflozin treatment demonstrated no persistent, clinically significant osmolarity volume, or renal status changes.