Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Biomed Res Int. 2017;2017:1253425. doi: 10.1155/2017/1253425. Epub 2017 Aug 15.
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors. LEADER, SUSTAIN-6, EMPA-REG OUTCOME, and CANVAS showed potential beneficial results, while the SAVOR-TIMI trial had an increased rate of hospitalization for heart failure. Meanwhile, the same drugs are investigated in preclinical experiments mainly using various animal models, which aim to find interactions and elucidate the underlying downstream mechanisms between the antihyperglycemic drugs and the cardiovascular system. Yet the direct link for observed effects, especially for DPP-4 and SGLT-2 inhibitors, is still unknown. Further inquiry into these mechanisms is crucial for the interpretation of the clinical trials' outcome and, vice versa, the clinical trials provide hints for an involvement of the cardiovascular system. The synopsis of preclinical and clinical data is essential for a detailed understanding of benefits and risks of new antihyperglycemic drugs.
在注册之前，必须对任何新开发的抗高血糖药物的心血管安全性进行评估，因为一项荟萃分析发出了警报，称噻唑烷二酮类药物罗格列酮会显著增加心肌梗死的风险。已可获得已完成心血管结局试验的初步结果：TECOS、SAVOR-TIMI 和 EXAMINE 研究了二肽基肽酶 4（DPP-4）抑制剂，ELIXA、LEADER 和 SUSTAIN-6 研究了胰高血糖素样肽 1（GLP-1）受体激动剂，而 EMPA-REG OUTCOME 和 CANVAS 研究了钠依赖性葡萄糖转运蛋白 2（SGLT-2）抑制剂。LEADER、SUSTAIN-6、EMPA-REG OUTCOME 和 CANVAS 显示出潜在的有益结果，而 SAVOR-TIMI 试验则导致心力衰竭住院率增加。与此同时，这些药物也在主要使用各种动物模型的临床前实验中进行了研究，旨在寻找抗高血糖药物与心血管系统之间的相互作用和阐明潜在的下游机制。然而，对于观察到的作用，特别是对于 DPP-4 和 SGLT-2 抑制剂，其直接联系仍然未知。进一步研究这些机制对于解释临床试验结果至关重要，反之，临床试验也为心血管系统的参与提供了线索。临床前和临床数据的概述对于详细了解新型抗高血糖药物的益处和风险至关重要。
