OBJECTIVE: To evaluate the effect of dipeptidyl-peptidase-4 (DPP-4) inhibitor vildagliptin on high sensitivity C-reactive protein (hsCRP) and arterial stiffness (AS) in patients with type 2 diabetes (T2DM).DESIGN: Sixty-four drug-naive diabetic patients, with inadequate glycemic control, participated in this randomized, open-label study. Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d. AS was measured by carotid-femoral Pulse Wave Velocity (cfPWV). Body weight (BW), body mass index (BMI), blood pressure (BP), hsCRP, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), lipid profile, albumin/creatinine ratio (ACR), fasting insulin, C-peptide, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were also assessed at baseline and after 6 months.RESULTS: Vildagliptin in combination with metformin had a beneficial influence on hsCRP, HbA1c, C-peptide and HOMA-β index (p <0.05) but had no effect on cfPWV, BP, BW, BMI, lipid profile, ACR and HOMA-IR compared with metformin alone (p=NS).CONCLUSIONS: We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP, improved glycemic control and β-cell function but had no effect on AS in drug-naive patients with T2DM.