The struggle with diabetes mellitus is a huge challenge for today’s mankind. The number of patients is growing daily. There are four basic forms of diabetes: type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes and other specific types of diabetes. It is estimated that in Croatia about 400 000 people have diabetes. Among those suffering from diabetes about 90 % are patients with type 2 diabetes mellitus. Genetic and external factors play a role in its development. Main causes are increased insulin resistance associated with obesity and impaired insulin secretion from the pancreas. Insulin resistance is mostly manifested in the liver and skeletal muscles. In type 2 diabetes mellitus increased endogenous glucose production is due to insulin resistance, whereas decreased intake and glucose utilization are present in skeletal muscles. Free fatty acids contribute to insulin resistance, gluconeogenesis in the liver and damage of β-cells. In type 2 diabetes mellitus the incretin effect is reduced, levels of glucagon are elevated and glucose reabsorption is increased in the kidneys. Decline of β-cells is affected by older age, a variant of the gene for the transcription factor TCF7L2, lipotoxicity, glucotoxicity and accumulation of amyloid deposits. Successful treatment of type 2 diabetes mellitus is important, because it is proven that achieving of the target value of blood glucose reduces developing of diabetes complications, especially microvascular complications. Combination therapy is a better approach than the traditional stepwise treatment approach. Drug groups used for the management of type 2 diabetes mellitus are: sulfonylurea derivatives and analogs, biguanides, thiazolidinediones, incretin mimetics, inhibitors of dipeptidyl peptidase-4, α-glucosidase inhibitors, inhibitors of sodium glucose co-transporter 2 and insulin preparations. It is recommended to achieve the level of glycated hemoglobin (HbA1c) less than 7 %, whereas the optimal value of HbA1c is less than 6.5 %. If started with the intensified approach, along with diagnosing diabetes mellitus, the outcome will be much more favorable. Besides, it is important to apply an individualized therapy approach for a patient in order to achieve better glycaemia control as less adverse side effects as possible.