Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
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DOI：
10.1371/journal.pone.0177646
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Park D
中科院分区：
文献类型：
--
作者：
Lee G;Oh SW;Hwang SS;Yoon JW;Kang S;Joh HK;Kwon H;Kim J;Park D
在2008年食品和药物管理局的行业指南中，在所有新的抗糖尿病药物的试验中应排除过度的心血管风险；然而，相对较少的研究关注于使用降糖药的心血管安全性。我们的目的是使用网络荟萃分析来检查死亡率和心血管风险。2016年3月，我们检索了Medline、Embase、Cochrane和ClinicalTrials.gov注册数据库，以确定报告下列口服降糖药心血管风险的随机对照试验：二甲双胍、磺脲类、噻唑烷二酮（TZD）、二肽基肽酶-4 （DPP4）抑制剂和钠-葡萄糖共转运蛋白-2 （SGLT2）抑制剂。我们评估了抗糖尿病药物在全因死亡率、心血管相关死亡率、急性冠状动脉综合征（ACS）和心肌梗死（MI）风险方面的差异，采用固定效应模型进行直接两两比较，并采用贝叶斯网络meta分析整合直接和间接比较。在73项随机对照试验的101183例患者中，3434例（3.4%）死亡。与安慰剂、二甲双胍、磺脲、TZD和DPP4抑制剂相比，使用SGLT2抑制剂的全因死亡率相对风险分别为0.68（95%可信区间：0.57-0.80）、0.74（0.49-1.10）、0.63（0.46-0.87）、0.71（0.55-0.90）和0.65（0.54-0.78）。与安慰剂、二甲双胍、磺脲、TZD和DPP4抑制剂相比，使用SGLT2抑制剂的心血管相关死亡率的相对风险分别为0.61（0.50-0.76）、0.81（0.36-1.90）、0.52（0.31-0.88）、0.66（0.49-0.91）和0.61（0.48-0.77）。使用SGLT2抑制剂的ACS相对风险与全因死亡率一致。SGLT2抑制剂的使用与其他oad和安慰剂相比，ACS的风险较低。与安慰剂和DPP4抑制剂相比，使用SGLT2抑制剂的心肌梗死相对风险分别为0.77（0.63-0.93）和0.75（0.60-0.94）。目前可用的数据提供了使用SGLT2抑制剂对2型糖尿病患者心血管有益的证据，尽管正在进行的研究的其他结果将是关键的。
In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57–0.80), 0.74 (0.49–1.10), 0.63 (0.46–0.87), 0.71 (0.55–0.90), and 0.65 (0.54–0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50–0.76), 0.81(0.36–1.90), 0.52(0.31–0.88), 0.66(0.49–0.91), and 0.61(0.48–0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63–0.93) and 0.75 (0.60–0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.