Campbell R Keith, Cobble Michael E, Reid Timothy S, Shomali Mansur E
Department of Pharmacotherapy, Washington State University College of Pharmacy, Pullman, WA, USA.
J Fam Pract. 2010 Sep;59(9 Suppl 1):S5-9.
The multifactorial nature of the pathogenesis of T2DM provides an opportunity to combine treatments that act upon different mechanisms. In addition to improving insulin resistance and pancreatic β-cell dysfunction, the GLP-1 agonists and DPP-4 inhibitors improve the impaired incretin response, as well as increase insulin secretion and reduce glucagon secretion, both in a glucose-dependent manner. As a result of these multiple actions, the GLP-1 agonists and DPP-4 inhibitors lower both fasting and postprandial glucose levels. The effects of GLP-1 agonists tend to be greater, probably because they produce pharmacologic levels of GLP-1 compared to physiologic levels with the DPP-4 inhibitors. Another difference is that unlike the DPP-4 inhibitors, the GLP-1 agonists also slow gastric emptying and promote satiety.
2型糖尿病发病机制的多因素性质为联合使用作用于不同机制的治疗方法提供了契机。胰高血糖素样肽-1（GLP-1）受体激动剂和二肽基肽酶-4（DPP-4）抑制剂除了可改善胰岛素抵抗和胰腺β细胞功能障碍外，还能改善受损的肠促胰岛素反应，并且以葡萄糖依赖的方式增加胰岛素分泌、减少胰高血糖素分泌。由于这些多重作用，GLP-1受体激动剂和DPP-4抑制剂可降低空腹和餐后血糖水平。GLP-1受体激动剂的作用可能更强，这可能是因为与DPP-4抑制剂产生的生理水平的GLP-1相比，GLP-1受体激动剂可产生药理水平的GLP-1。另一个不同之处在于，与DPP-4抑制剂不同，GLP-1受体激动剂还可延缓胃排空并促进饱腹感。
