Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Women's College Research Institute, Department of Medicine, Women's College Hospital, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Trends Cardiovasc Med. 2017 Apr;27(3):194-202. doi: 10.1016/j.tcm.2017.01.009. Epub 2017 Jan 28.
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure. Evidence for cardiovascular benefits of glucagon-like peptide-1 (GLP-1) agonists has been similarly heterogeneous, with liraglutide and semaglutide reducing the risk of composite cardiovascular outcomes, but lixisenatide having no reduction or increase in cardiovascular risk. The effect of GLP-1 agonists on retinopathy remains a potential concern. In the only completed trial to date to assess a sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin reduced the risk of composite cardiovascular endpoints, predominantly through its impact on cardiovascular mortality and heart failure hospitalization.
本文回顾了美国食品和药物管理局要求进行的大型、双盲、安慰剂对照随机临床试验的结果，以检查新批准的抗高血糖药物在 2 型糖尿病患者中的心血管安全性。二肽基肽酶-4（DPP-4）抑制剂的心血管作用仍存在争议：虽然这些药物没有降低或增加主要预先指定的复合心血管结局的风险，但一种 DPP-4 抑制剂（沙格列汀）增加了心力衰竭住院的风险在总体人群中；另一种（阿格列汀）在患者亚组中对心力衰竭住院的影响不一致，第三种（西格列汀）对心力衰竭无影响。胰高血糖素样肽-1（GLP-1）激动剂的心血管获益证据也同样存在异质性，利拉鲁肽和司美格鲁肽降低了复合心血管结局的风险，但 lixisenatide 对心血管风险没有降低或增加。GLP-1 激动剂对视网膜病变的影响仍然是一个潜在的关注点。在迄今为止唯一评估钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂的完成试验中，恩格列净降低了复合心血管终点的风险，主要通过其对心血管死亡率和心力衰竭住院的影响。
