The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin or insulin plus rosiglitazone groups for six months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups except for insulin plus acarbose group. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and insulin plus metformin (2%) groups. Daily total insulin dose increased 12.7 units/day in insulin alone group, decreased 4.7 units/day in insulin plus rosiglitazone group, 4.2 units/day in insulin plus metformin group, and 2.7 units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4 kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6 kg). Except for the improvement of total cholesterol levels in insulin plus rosiglitazone group, no significant change in lipid levels was observed in any groups. CRP levels decreased significantly both in insulin plus metformin and insulin plus rosiglitazone groups. Fibrinogen levels decreased in insulin alone, insulin plus metformin, and insulin plus rosiglitazone groups. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group.