Aim. To investigate the efficacy and safety of combined glimepiride and metformin therapy in patients with type 2 diabetes mellitus (T2DM). Materials and methods. A multi-centre, open-label, prospective, observational study was conducted. A total of 1200 patients with T2DM inadequately controlled with metformin, glimepiride or combination of metformin + glimepiride were enrolled. Change in serum glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial blood glucose (PPG) levels; weight; waist circumference and hypoglycemic episodes were evaluated. Results. Baseline HbA1c levels (8.24% ? 0.42%) were significantly reduced after 12 weeks of treatment (7.48% ? 0.48%) and at the end of the study. (6.88% ? 0.56%). Target HbA1c levels (?7%) were achieved in 65.1% of patients at the final visit at 24 weeks. FPG and PPG levels decreased by 1.45 ? 1.14 mmol/l and 2.17 ? 1.27 mmol/l respectively (p < 0.001). No severe hypoglycemic events were reported. Body mass index reduced by 0.85 ? 1.28 kg/m2 (p < 0.001). Conclusion. . Combined glimepiride and metformin therapy significantly improved long-term glycemic control in patients with T2DM during the period of 24 weeks. without additional risk of hypoglycemic events or weight gain.