胰高糖素样肽-1受体激动剂CVOT结果异同的解读

Interpretation of the Similarities and Differences in CVOT Results of Glucagon-like Peptide 1 Receptor Agonists

心血管结局试验(cardiovascular outcome trial,CVOT)的结果显示胰高糖素样肽1受体激动剂(glucagon-like peptide-1 receptor agonists,GLP-1 RA)具有降低2型糖尿病(type 2 diabetes mellitus,T2DM)患者心血管事件的特点,而且是非血糖依赖性。据此,国内外指南对GLP-1 RA的使用建议也在不断地更新。GLP-1 RA这些降糖外作用各具特点,且非所有GLP-1 RA共有,是各种药物的自身特点或是同类药物的类效应还不确定。各项CVOT患者的临床特征、药物来源和给药方式等方面的差异并不能说明各种CVOT结果的不同。高浓度和长时间的暴露可能部分解释不同GLP-1 RA非降糖作用的差别,但需要进一步的研究证实。

The results of cardiovascular outcome trials(CVOTs)show that glucagon-like peptide-1 receptor agonists(GLP-1 RA)have the effect of reducing cardiovascular events in patients with type 2 diabetes(T2DM)and this effect is independent of blood glucose.Given these evidences,the recommendations about use of GLP-1 RA in domestic and foreign guidelines are updated repeatedly.These effects of GLP-1 RA beyond lowering glucose are heterogeneous and are not shown by all the GLP-1 RAs.It is still uncertain whether they are the characteristics of different drugs or the class effects.The differences in CVOTs results cannot be attributed to the differences of clinical characteristics of patients,drug sources,and administration methods in different CVOTs.High concentration and long-term exposure may partly explain the differences in non-hypoglycemic effects of different GLP-1 RAs,but further studies are needed to confirm this viewpoint.