钠-葡萄糖协同转运蛋白 2 抑制剂达格列净在 2 型糖尿病合并 3b-4 期慢性肾脏病患者中的作用。
Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease.
机构信息
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Centre for Nephrology, University College London, London, UK.
出版信息
Nephrol Dial Transplant. 2018 Nov 1;33(11):2005-2011. doi: 10.1093/ndt/gfx350.
BACKGROUND
The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease (CKD).
METHODS
In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined least square mean changes in HbA1c, body weight, BP, estimated glomerular filtration rate (eGFR) and UACR over 102 weeks in patients with type 2 diabetes and an eGFR between 12 to less than 45 mL/min/1.73 m2 receiving placebo (n = 69) or dapagliflozin 5 or 10 mg (n = 151). Effects on UACR were determined in a subgroup of patients with baseline UACR ≥30 mg/g (n = 136).
RESULTS
Placebo-corrected changes in HbA1c with dapagliflozin 5 and 10 mg were 0.03% [95% confidence interval (CI) -0.3-0.3] and 0.03% (95% CI -0.2-0.3) during the overall 102-week period. Dapagliflozin 5 and 10 mg compared with placebo reduced UACR by - 47.1% (95% CI -64.8 to - 20.6) and -38.4% (95% CI -57.6 to - 10.3), respectively. Additionally, dapagliflozin 5 and 10 mg compared with placebo reduced BP and body weight. eGFR increased with placebo during the first 4 weeks but did not change with dapagliflozin. There were no between-group differences in eGFR at the end of follow-up. Adverse events associated with renal function occurred more frequently in the dapagliflozin 10-mg group. These events were mainly asymptomatic increases in serum creatinine.
CONCLUSIONS
Dapagliflozin did not decrease HbA1c in patients with type 2 diabetes and Stages 3b-4 CKD, but decreased UACR, BP and body weight to a clinically meaningful extent. These results support a large outcome trial in this population to confirm long-term safety and efficacy in reducing adverse clinical endpoints.
背景
钠-葡萄糖协同转运蛋白 2 抑制剂达格列净可降低 2 型糖尿病患者的血红蛋白 A1c（HbA1c）、体重、血压（BP）和尿白蛋白：肌酐比值（UACR）。该药在 2 型糖尿病合并 3b-4 期慢性肾脏病（CKD）患者中的疗效和安全性尚未得到充分明确。
方法
在 11 项 3 期随机对照临床试验的汇总分析中，我们确定了接受安慰剂（n=69）或达格列净 5 或 10mg（n=151）治疗的 2 型糖尿病且 eGFR 在 12 至<45mL/min/1.73m2 之间的患者在 102 周内 HbA1c、体重、BP、估算肾小球滤过率（eGFR）和 UACR 的最小平方均值变化。在基线 UACR≥30mg/g（n=136）的亚组患者中确定了 UACR 的影响。
结果
达格列净 5mg 和 10mg 与安慰剂相比，HbA1c 的安慰剂校正变化在整个 102 周期间分别为 0.03%（95%置信区间[CI] -0.3 至 0.3）和 0.03%（95% CI -0.2 至 0.3）。达格列净 5mg 和 10mg 与安慰剂相比，分别使 UACR 降低了 -47.1%（95% CI -64.8 至 -20.6）和 -38.4%（95% CI -57.6 至 -10.3）。此外，达格列净 5mg 和 10mg 与安慰剂相比，还降低了 BP 和体重。eGFR 在最初的 4 周内随安慰剂而增加，但达格列净不会改变 eGFR。在随访结束时，两组之间的 eGFR 无差异。肾功能相关的不良事件在达格列净 10mg 组中更为常见。这些事件主要是无症状的血清肌酐升高。
结论
达格列净未降低 2 型糖尿病合并 3b-4 期 CKD 患者的 HbA1c，但以有临床意义的程度降低了 UACR、BP 和体重。这些结果支持在该人群中进行一项大型结局试验，以确认长期安全性和降低不良临床终点的疗效。
Zotero 插件