Sodium-glucose co-transporter (SGLT2) inhibitors represent the latest oral agents for type 2 diabetes treatment. SGLT2 is mainly expressed in the kidneys and are responsible for the renal handling of the glucose load. The insulin-independent mechanism of action, targeting the kidneys, differentiates the SGLT2 inhibitors from any existing antidiabetic agent. Thus, it is hypothesized that SGLT2 inhibitors can be effectively combined with other antidiabetic agents, including insulin, either as monotherapy or in dual or triple combinations. The evidence so far shows that SGLT2 inhibitors are as effective as established antidiabetic agents such as metformin or sulfonylureas in their ability to lower HbA1c. On the other hand, SGLT2 inhibitors increase the possibility of genitourinary infections.