Effects of Sitagliptin on the Coronary Flow Reserve, Circulating Endothelial Progenitor Cells and Stromal Cell-derived Factor-1alpha

OBJECTIVE: Circulating endothelial progenitor cells (EPCs) are regulated by stromal cell-derived factor-1alpha (SDF-1α) and are reduced in type 2 diabetes mellitus (DM). SDF-1α is a substrate of dipeptidyl-peptidase-4 (DPP-4), so we investigated whether or not DPP-4-inhibitors modulate EPC levels in type 2 DM patients with coronary artery disease (CAD). METHODS: Thirty patients with CAD and type 2 DM treated using an ordinary regimen were enrolled. EPC and SDF-1α levels were compared between those receiving additional 24-week treatment with a DPP-4-inhibitor (n=11) and no additional treatment (n=19). We determined the HbA1c, 1.5-Anhydro-D-glucitol (1,5-AG), coronary flow reserve (CFR), brain natriuretic peptide (BNP), E/e', and circulating EPC proportion and SDF-1α levels at baseline and the end of follow-up. The CFR was assessed using a dual-sensor-equipped guidewire. The primary endpoints were changes in the EPC count, SDF-1α levels, and CFR from baseline to the end of follow-up. The secondary endpoints were changes in the HbA1c and 1,5-AG, which are useful clinical markers of postprandial hyperglycemia, as well as the BNP and E/e'. RESULTS: After the 6-month follow-up, compared with ordinary regimen subjects, the patients receiving a DPP-4-inhibitor showed no significant increase in the EPC proportion (−0.01±0.50 vs. 0.02±0.77%, p=0.87), SDF-1α level (−600.4±653.6 vs. −283.2±543.1 pg/mL, p=0.18), or CFR (0.0±0.2 vs. 0.1±0.6, p=0.20), whereas both the 1.5-AG level (2.4±4.6 vs. −0.7±2.5 μg/dL, p=0.07) and HbA1c (−0.8±1.8 vs. 0.0±0.7%, p=0.02) were improved. There were no significant differences between the two groups in changes in the BNP and E/e'. CONCLUSION: DPP-4 inhibition with sitagliptin did not increase or decrease the EPC proportion, SDF-1α level, or CFR, although the glycemic control was improved.