Division of Endocrinology, Duke University Medical Center, Durham, NC 27705, USA.
Postgrad Med. 2012 Jul;124(4):54-61. doi: 10.3810/pgm.2012.07.2566.
The dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of oral antidiabetic agents that improve glycemic control in patients with type 2 diabetes mellitus. These agents differ in structure, but all act by inhibiting the DPP-4 enzyme. Dipeptidyl peptidase-4 inhibition increases levels of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which in turn stimulate insulin secretion in a glucose-dependent fashion. Clinical trials have shown that DPP-4 inhibitors provide significant reductions in glycated hemoglobin levels, with a low risk of hypoglycemia. Animal model experiments and proof-of-concept studies suggest that the incretins favorably affect the cardiovascular system; it is possible that these same effects may be conveyed by DPP-4 inhibitor therapy. Pooled and meta-analyses of DPP-4 inhibitor clinical trial data have shown no increase in major adverse cardiovascular events, and, in fact, suggest a potential cardiovascular benefit to such therapy. Long-term cardiovascular safety trials are currently underway to more fully define and understand the cardiovascular impact of DPP-4 therapy in patients with type 2 diabetes mellitus.
二肽基肽酶-4（DPP-4）抑制剂是一类新型的口服抗糖尿病药物，可改善 2 型糖尿病患者的血糖控制。这些药物在结构上有所不同，但都通过抑制 DPP-4 酶起作用。DPP-4 抑制可增加肠促胰岛素激素胰高血糖素样肽-1 和葡萄糖依赖性胰岛素释放肽的水平，进而以葡萄糖依赖性方式刺激胰岛素分泌。临床试验表明，DPP-4 抑制剂可显著降低糖化血红蛋白水平，且低血糖风险较低。动物模型实验和概念验证研究表明，肠促胰岛素对心血管系统有有利影响；DPP-4 抑制剂治疗可能也具有相同的作用。对 DPP-4 抑制剂临床试验数据的汇总和荟萃分析显示，主要不良心血管事件无增加，实际上，此类治疗可能具有潜在的心血管获益。目前正在进行长期心血管安全性试验，以更全面地定义和了解 DPP-4 治疗在 2 型糖尿病患者中的心血管影响。
