OBJECTIVE We investigated the effect of alogliptin and gliclazide on endothelial progenitor cells (EPCs) in type 2 diabetes. METHODS Eighty patients with type 2 diabetes and HbA1c between 7.5% and 8.5% were randomized to receive either alogliptin (25 mg/daily) or gliclazide extended-release (30 mg/daily for HbA1c 7.5-8.0% and 60 mg/daily for HbA1c 8.0-8.5%) in combination with metformin for 4 months. At baseline and 4 months, clinical and laboratory parameters of EPCs were determined. RESULTS After 4 months of treatment, alogliptin and gliclazide resulted in a similar significant reduction in HbA1c (%) (8.0±0.3 vs. 7.1±0.2, and 8.0±0.3 vs. 7.0±0.2, respectively; P<0.05) and a similar and significant increase in EPC count (cells/106 WBC) (CD45-CD133+KDR+ : 2.2±1.2 vs. 3.7±1.6, CD45-CD34+KDR+: 3.3±1.8 vs. 4.9±1.8; P<0.05 for alogliptin; CD45-CD133+KDR+: 2.3±1.3 vs. 3.6±1.5, CD45-CD34+KDR+: 3.1±1.3 vs. 4.6±1.7; P<0.05 for gliclazide). CONCLUSIONS Both alogliptin and gliclazide demonstrated a beneficial effect in increasing EPCs in poorly controlled type 2 diabetes. As alogliptin and gliclazide exhibit different mechanisms of action, the observed increase in EPCs seems to be due to their glucose-lowering effect.