SGLT2 抑制剂对 2 型糖尿病合并慢性肾脏病患者心血管、肾脏和安全性结局的影响：系统评价和荟萃分析。

Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta-analysis.

机构信息

Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Australia.

Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan.

出版信息

Diabetes Obes Metab. 2019 May;21(5):1237-1250. doi: 10.1111/dom.13648. Epub 2019 Mar 4.

DOI:10.1111/dom.13648

PMID:30697905

Abstract

AIM

The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta-analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m .

MATERIALS AND METHODS

We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals.

RESULTS

Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (-0.29%; 95% CI, -0.39 to -0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70-0.94) and heart failure (RR, 0.61; 95% CI, 0.48-0.78), without a clear effect on all-cause mortality (HR, 0.86; 95% CI, 0.73-1.01). These agents also attenuated the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73 m /y; 95% CI, 0.78-1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53-0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes.

CONCLUSION

Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.

摘要

目的

钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂在 2 型糖尿病（T2DM）合并慢性肾脏病（CKD）患者中的应用受到限制，主要是因为血糖疗效依赖于肾功能。我们进行了一项系统评价和荟萃分析，以评估 SGLT2 抑制剂在 T2DM 合并 CKD 患者（定义为估算肾小球滤过率[eGFR]＜60mL/min/1.73m ）中的疗效和安全性。

材料和方法

我们检索了 MEDLINE、EMBASE 和 Cochrane 图书馆，检索时间截至 2018 年 8 月 7 日，并检索了美国、欧洲和日本监管机构的网站，检索时间截至 2018 年 7 月 27 日，以获取 SGLT2 抑制剂的随机对照试验数据，这些试验报告了 T2DM 合并 CKD 患者的生物标志物、心血管、肾脏或安全性结局的影响。使用随机效应模型和倒数方差加权法计算 95%置信区间的相对风险。

结果

共有 27 项研究的数据纳入了多达 7363 名参与者。在 T2DM 合并 CKD 患者中，SGLT2 抑制剂降低糖化血红蛋白（-0.29%；95%CI，-0.39 至-0.19）以及血压、体重和白蛋白尿。SGLT2 抑制降低了心血管死亡、非致死性心肌梗死或非致死性卒中（RR，0.81；95%CI，0.70-0.94）和心力衰竭（RR，0.61；95%CI，0.48-0.78）的风险，全因死亡率无明显变化（HR，0.86；95%CI，0.73-1.01）。这些药物还减弱了 eGFR 斜率的年度下降（安慰剂减去的差值为 1.35mL/1.73m /y；95%CI，0.78-1.93），并降低了复合肾脏结局的风险（HR，0.71；95%CI，0.53-0.95）。虽然在一些安全性结局中观察到个体药物之间存在异质性，但在 CKD 中，SGLT2 抑制的安全性风险并不超过该类药物已知的风险。