钠-葡萄糖共转运蛋白 2 抑制剂在 2 型糖尿病患者中的心血管安全性、长期非心血管安全性和疗效：系统评价和试验序贯分析。

Cardiovascular Safety, Long-Term Noncardiovascular Safety, and Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis With Trial Sequential Analysis.

机构信息

Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

J Am Heart Assoc. 2018 Jan 20;7(2):e007165. doi: 10.1161/JAHA.117.007165.

BACKGROUND

The cardiovascular and long-term noncardiovascular safety and efficacy of SGLT2 (sodium-glucose cotransporter 2) inhibitors have not been well documented.

METHODS AND RESULTS

For cardiovascular outcomes, we performed a meta-analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient-years of follow-up. For long-term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient-years of follow-up. Five studies with 351 476 patients were included in cardiovascular outcomes analysis. Meta-analyses showed that SGLT2 inhibitors significantly reduced the risks of major adverse cardiac events (hazard ratio [HR]: 0.80; 95% confidence interval [CI], 0.69-0.92; =0.002), all-cause mortality (HR: 0.67; 95% CI, 0.54-0.84; <0.001), cardiovascular mortality (HR: 0.77; 95% CI, 0.60-0.98; =0.03), nonfatal myocardial infarction (HR: 0.86; 95% CI, 0.76-0.98; =0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55-0.69; <0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58-0.81; <0.001). No significant difference in nonfatal stroke was found. Analyses limited to randomized controlled trials showed similar findings. Trial sequential analysis provided firm evidence of a 20% reduction in major adverse cardiac events, all-cause mortality, and hospitalization for heart failure with SGLT2 inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine randomized controlled trials contributed to long-term noncardiovascular and efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute kidney injury but increased the risks of urinary tract and genital infections.

CONCLUSIONS

SGLT2 inhibitors showed remarkable cardiovascular- and renal-protective effects and good long-term noncardiovascular safety with sustained efficacy.

背景

SGLT2（钠-葡萄糖协同转运蛋白 2）抑制剂的心血管和长期非心血管安全性和疗效尚未得到充分证实。

方法和结果

对于心血管结局，我们进行了一项荟萃分析，采用试验序贯分析随机对照试验和调整后的观察性研究，每个研究的随访时间至少为 26 周和 2000 患者-年。对于长期非心血管安全性和疗效结局分析，我们仅纳入了随访时间至少 2 年和 1000 患者-年的随机对照试验。纳入了 5 项研究共 351476 名患者进行心血管结局分析。荟萃分析显示 SGLT2 抑制剂显著降低了主要不良心脏事件（风险比 [HR]：0.80；95%置信区间 [CI]：0.69-0.92；=0.002）、全因死亡率（HR：0.67；95%CI：0.54-0.84；<0.001）、心血管死亡率（HR：0.77；95%CI：0.60-0.98；=0.03）、非致死性心肌梗死（HR：0.86；95%CI：0.76-0.98；=0.02）、心力衰竭住院（HR：0.62；95%CI：0.55-0.69；<0.001）和蛋白尿进展（HR：0.68；95%CI：0.58-0.81；<0.001）的风险。未发现非致死性卒中的差异。仅限于随机对照试验的分析得出了类似的发现。试验序贯分析提供了 SGLT2 抑制剂可降低 20%主要不良心脏事件、全因死亡率和心力衰竭住院风险的可靠证据，但心血管死亡率的证据仍不确定。9 项随机对照试验为长期非心血管和疗效分析做出了贡献。SGLT2 抑制剂降低了低血糖和急性肾损伤的发生率，但增加了尿路感染和生殖系统感染的风险。