Aronow Wilbert S, Shamliyan Tatyana A
Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA.
Evidence-Based Medicine Center, Elsevier, Philadelphia, PA, USA.
Ann Transl Med. 2017 Dec;5(23):455. doi: 10.21037/atm.2017.08.43.
Based on a single placebo-controlled randomized clinical trial, empagliflozin is licensed to reduce cardiovascular death in diabetes and comorbid cardiovascular disease.
We examined the comparative effectiveness of empagliflozin on mortality and cardiovascular morbidity in type 2 diabetes. We conducted random-effects direct frequentist meta-analyses of aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to May 2017 identified 11 meta-analyses, multiple publications, and unpublished data from 29 randomized controlled trials (RCTs).
Empagliflozin reduces all-cause mortality [relative risk (RR) of death, 0.69; 95% confidence interval (CI): 0.58-0.82; number needed to treat (NNT) to postpone mortality in one patient, 39; 95% CI: 26-79; 1 RCT of 7,020 patients) in patients with but not without (RR, 0.90; 95% CI: 0.36-2.23; 14 RCTs of 7,707 patients) established cardiovascular disease when compared with placebo. Empagliflozin reduces cardiovascular mortality (RR, 0.62; 95% CI: 0.50-0.78; NNT, 45; 95% CI: 30-90; 1 RCT of 7,020 patients) in patients with but not without (RR, 0.98; 95% CI: 0.29-3.33; 10 RCTs of 5,429 patients) established cardiovascular disease when compared with placebo. There are no differences in cardiovascular morbidity and mortality and all-cause mortality between empagliflozin and metformin (4 RCTs of 1,344 patients), glimepiride (1 RCT of 1,549 patients), linagliptin (2 RCTs of 1,348 patients), or sitagliptin (3 RCTs of 1,483 patients). Two network meta-analyses concluded that sodium-glucose cotransporter 2 (SGLT2) inhibitors, mostly due to empagliflozin, decrease all-cause and cardiovascular mortality but increase the risk of nonfatal stroke, genital infection, and volume depletion.
We conclude that empagliflozin reduces all-cause and cardiovascular mortality in patients with established cardiovascular disease and type 2 diabetes. Sparse direct evidence suggests no difference in mortality between empagliflozin and metformin, glimepiride, linagliptin, or sitagliptin. Long-term comparative safety needs to be established.
基于一项单安慰剂对照随机临床试验，恩格列净被批准用于降低糖尿病合并心血管疾病患者的心血管死亡风险。
我们研究了恩格列净对2型糖尿病患者死亡率和心血管疾病发病率的比较效果。我们对汇总数据进行了随机效应直接频率元分析，并使用推荐分级评估、制定和评价（GRADE）方法评估证据质量。截至2017年5月，我们在PubMed、EMBASE、Cochrane图书馆、clinicaltrials.gov和PharmaPendium中进行检索，共识别出11项元分析、多篇出版物以及来自29项随机对照试验（RCT）的未发表数据。
与安慰剂相比，恩格列净可降低已确诊心血管疾病患者的全因死亡率[死亡相对风险（RR）为0.69；95%置信区间（CI）：0.58 - 0.82；使1例患者推迟死亡所需治疗人数（NNT）为39；95% CI：26 - 79；1项纳入7020例患者的RCT]，而对未患心血管疾病的患者无此效果（RR为0.90；95% CI：0.36 - 2.23；14项纳入7707例患者的RCT）。与安慰剂相比，恩格列净可降低已确诊心血管疾病患者的心血管死亡率（RR为0.62；95% CI：0.50 - 0.78；NNT为45；95% CI：30 - 90；1项纳入7020例患者的RCT），而对未患心血管疾病的患者无此效果（RR为0.98；95% CI：0.29 - 3.33；10项纳入5429例患者的RCT）。恩格列净与二甲双胍（4项纳入1344例患者的RCT）、格列美脲（1项纳入1549例患者的RCT）、利格列汀（2项纳入1348例患者的RCT）或西格列汀（3项纳入1483例患者的RCT）在心血管疾病发病率、死亡率和全因死亡率方面无差异。两项网状元分析得出结论，钠 - 葡萄糖协同转运蛋白2（SGLT-2）抑制剂，主要是由于恩格列净，可降低全因和心血管死亡率，但会增加非致命性中风、生殖器感染和容量耗竭的风险。
我们得出结论，恩格列净可降低已确诊心血管疾病的2型糖尿病患者全因死亡率和心血管死亡率。稀疏的直接证据表明，恩格列净与二甲双胍、格列美脲、利格列汀或西格列汀在死亡率方面无差异。需要确定其长期比较安全性。
