We read with interest the recently published review by Chrysant and Chrysant on the clinical implications of cardiovascular preventing pleiotropic effects of dipeptidyl peptidase–4 (DPP-4) inhibitors. In their review, the investigators pointed out that all actions of DPP-4 inhibitors are mediated through the incretins glucagon-like peptide–1 (GLP-1) and glucose-dependent insulinotropic polypeptide. However, there are some negative results. A study by Yin et al showed that the DPP-4 inhibitor vildagliptin has no substantial protective effects on cardiac function, despite increasing the active GLP-1 level in long-term post–myocardial infarction cardiac remodeling model, indicating that incretin GLP-1 may be not the independent pathway mediating cardiovascular preventing effects. Furthermore, the DPP-4 inhibitors can block the degradation of stromal-derived factor–1α, which is a physiologic substrate of DPP-4. It was found that DPP-4 inhibitors stimulate bone marrow mobilization of endothelial progenitor cells through the stromal-derived factor–1α/C-X-C chemokine receptor type 4 axis, which in turn affects endothelial progenitor cell–mediating cardiovascular repair. In addition, DPP-4 inhibitors can improve lipid metabolism. Boschmann et al pointed out that DPP-4 inhibitors increase postprandial lipid mobilization and oxidation via activating the sympathetic nervous system rather than the direct effect on metabolic status. Although the GLP-1 mechanism is very important in cardiovascular effects of DPP-4 inhibitors, these studies indicate that some other pathways might have been involved in these effects. Taken together, these data suggest that DPP-4 inhibitors are likely to exert important cardiovascular effects beyond GLP-1 or glycemic control. Therefore, it may not be appropriate to state that all actions of DPP-4 inhibitors are mediated through the incretins GLP-1 and glucose-dependent insulinotropic polypeptide.