Aim. To evaluate the efficiency and safety of early combination therapy with sulfonylurea derivatives (SUD) and insulin sensitizers in patients with type 2 diabetes mellitus (T2DM). Subjects and methods. Forty patients (31 women and 9 men; mean age 57.7 +/- 0.9 years) with decompensatecl T2DM (HbA(1c) 8.16 +/- 0.27%), a mean body mass index of 32.7 +/- 0.7 kg/m(2), who received glimepiride, were examined. The duration of T2DM was 3.3 +/- 0.4 years. The patients had concomitant cardiovascular diseases (CVD). Coronary heart disease and hypertensive disease (HD) were treated; the closes of the agents were not adjusted during the study. For T2DM compensation, all the patients were given insulin sensitizers (rosiglitazone 4 mg) in addition to glimepiride. The treatment lasted 24 weeks. Carbohydrate and lipid metabolic parameters, insulin resistance, body weight, structural and functional parameters, and heart rate were estimated before and after the treatment. Results. During the combination therapy, there were decreases in the level of HbA(1c), from 8.16 +/- 0.27 to 6.84 +/- 0.15%, fasting blood glucose from 8.89 +/- 0.35 to 6.77 +/- 0.16 mmol/l, postprandial blood glucose from 8.66 +/- 0.24 to 7.761 +/- 0.20 mmol/l, HOMA index from 5.88 +/- 0.70 to 3.75 +/- 0.44. The rate of hypoglycemic reaction reduced. Sugar-lowering therapy was observed to have, on average, a positive impact on blood lipid composition and cardiovascular parameters in the group. Echocardiography (EchoCG) identified a group of patients with negative cardiac structural and functional changes. Conclusion. The combination therapy with SUD and insulin sensitizers was stated to be effective in maintaining the reached blood glucose level, reducing the risk of hypoglycemic reactions, and positively affecting lipid metabolism. The therapy resulted in cardiovascular improvement only in patients without obvious signs of CVD while it caused negative EchoCG changes (transformation of concentric to eccentric left ventricular hypertrophy) in patients with a long-term (more than 7 years) history of HD and pronounced cardiac structural and functional alterations.