Introduction: Despite the availability of various medications for type 2 diabetes (T2DM), treatment quality remains inadequate, leading to increased complications. Therefore, the introduction into health care practice of optimal methods of strategy and tactics of glucose-lowering therapy at the present stage, as a measure to prevent the development of its complications, is one of the pressing problems of diabetology. The purpose of the study was to evaluate the dynamics of hormonal and metabolic parameters in patients with type 2 diabetes during treatment with glimepiride, repaglinide and metformin from 4.5 years to 5 years. Materials and Methods: The conducted study belongs to a randomized controlled clinical trial. Patients with type 2 diabetes (T2DM) were divided into groups (n=280) based on treatment with glimepiride, repaglinide, metformin, or gliclazide (control). The study assessed hormonal and metabolic parameters over 3 months to 5 years. The nature of the study is clinical, comparative and prospective. The effectiveness of various drugs (glimepiride, repaglinide, metformin) in the treatment of type 2 diabetes mellitus was compared, tracking the dynamics of various indicators over a long period. Results: Glimepiride demonstrated superior glycemic control and lipid management compared to gliclazide. Only a small percentage of patients achieved optimal HbA1c levels, while many experienced suboptimal or decompensated control. Glimepiride was associated with a lower risk of decompensation compared to other sulfonylurea drugs. Conclusion: Glimepiride, repaglinide, and metformin each demonstrated distinct advantages in managing type 2 diabetes. Glimepiride and repaglinide effectively reduced blood sugar levels and glycosylated hemoglobin, while metformin was particularly effective in early-stage disease. Individualized treatment plans, including combination therapies, can improve patient outcomes and quality of life.