The review deals with the prospect substantiation for using combined therapy by oral antihyperglycemic drugs with different mechanisms of action (metformin + sulfonylureas) and insulin for type 2 diabetes mellitus. The second oral drug is advisable to add, when the average doses of the first drug do not provide full effectiveness, and, since the doses of non-insulin antihyperglycemic drugs are usually not increased to a maximum, the side effects are reduced. Also, a combination of heterogeneous antidiabetic effects within and beyond the glycemic control, which is characteristic of biguanide (metformin), sulfonylurea (glimepiride) and insulin combination, such as reduction of hypoadiponectinemia, dyslipidemia, oxidative stress, inflammation, vascular endothelial cell dysfunction, elimination of «hyperglycemic memory», preservation the phenomenon of ischemic preconditioning, increased pancreatic β-cell survival rate, etc., provides further advantages in the treatment of type 2 diabetes mellitus, as well as in the prevention and treatment of cardiovascular complications.