Diabetology, University of Florence, Italy.
Diabetology, University of Florence, Italy.
Nutr Metab Cardiovasc Dis. 2019 Mar;29(3):215-219. doi: 10.1016/j.numecd.2018.12.009. Epub 2019 Jan 3.
Dypeptidylpeptidase-4 (DPP-4) inhibitors are a therapeutic option for improving glucose control in patients with type 2 diabetes. They can be prescribed at different stages of the natural history of the disease because of their low risk for hypoglycemia and associated weight gain. For all new drugs for diabetes, the US Food and Drug Administration requires the demonstration of the cardiovascular (CV) safety profile through pooled analyses of phase 3 studies or specifically designed trials. A significant superiority over placebo has been observed with a sodium-dependent glucose transporter-2 inhibitor, empagliflozin, and two glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, thus suggesting cardioprotective effects for some antidiabetic drugs. The neutral results of CV safety trials on DPP-4 inhibitors have been disappointing, appearing to contradict the data from pooled analyses and meta-analyses of early trials. The main aim of this review is to find a possible interpretation for the differences between the results of these early trials and the CV safety studies with DPP-4 inhibitors. We conclude that the hypothesis of additional beneficial effects by DPP-4 inhibitors (beyond the improvement of glucose control), on the CV system in low-risk patients in primary prevention, needs to be verified with specifically designed studies.
二肽基肽酶-4（DPP-4）抑制剂是改善 2 型糖尿病患者血糖控制的一种治疗选择。由于低血糖和体重增加的风险低，它们可以在疾病的自然史的不同阶段开处方。对于所有新的糖尿病药物，美国食品和药物管理局（FDA）要求通过 3 期研究的汇总分析或专门设计的试验来证明心血管（CV）安全性概况。钠依赖性葡萄糖转运蛋白-2 抑制剂恩格列净（empagliflozin）和两种胰高血糖素样肽-1 受体激动剂利拉鲁肽（liraglutide）和司美格鲁肽（semaglutide）与安慰剂相比具有显著的优越性，因此表明一些抗糖尿病药物具有心脏保护作用。DPP-4 抑制剂的 CV 安全性试验的中性结果令人失望，似乎与汇总分析和早期试验的荟萃分析数据相矛盾。本综述的主要目的是为这些早期试验和 DPP-4 抑制剂的 CV 安全性研究之间的结果差异寻找一个可能的解释。我们的结论是，需要通过专门设计的研究来验证 DPP-4 抑制剂（除了改善血糖控制之外）对低风险患者一级预防中的 CV 系统的额外有益作用的假说。
