A recent study published in Expert Opinion on Pharmacotherapy compared the effects of vildagliptin and glimepiride on glycemic variability, oxidative stress, and endothelial parameters in patients with type-2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. This randomized, open-label, parallel study, allocated 34 patients with T2DM on metformin, having an HbA1c of 7.0-10.0%, into either the vildagliptin or glimepiride group. Subsequently, urinary 8-iso-prostaglandinF_2α (PGF_2α) and endothelial-dependent flow-mediated dilatation (FMD) were evaluated at baseline and after 12 weeks of treatment. The results revealed equivalent notable improvements in HbA1c levels, in both vildagliptin (-0.8%) and glimepiride (-0.9%) groups post-treatment. It was observed that the mean amplitude of glycemic excursions (MAGE) and the mean of daily differences (MODD) were significantly decreased by vildagliptin, but not by glimepiride. On the contrary, vildagliptin was associated with a lower incidence of hypoglycemia. Whereas, there were no significant differences in urinary 8-iso-PGF_2α or FMD between the two groups. Hence, it was concluded that vildagliptin effectively improves glucose level with a significantly greater reduction in glycemic variability and hypoglycemia in patients with T2DM ongoing metformin therapy.