Clinical use of thiazolidinediones: recommendations

Type 2 diabetes mellitus is characterized by progressive beta-cell secretory dysfunction against a background of insulin resistance, which is present many years before the onset of hyperglycemia in most patients. Intensive treatment of diabetes reduces the risk of the onset and progression of microvascular complications and may impact the risk of development of macrovascular complications, notably coronary artery disease. Therefore, aggressive treatment with the goal of achieving serum glucose concentrations as close to normal as possible is warranted. Although medical nutritional therapy and exercise remain the cornerstones of therapy for type 2 diabetes, >90% of patients ultimately require pharmacologic therapy, and most need >1 agent to achieve therapeutic objectives. When considering which agent or agents to use to treat type 2 diabetes, one must consider the mechanism of action of the drug, its ability to lower serum glucose concentrations, the durability of effect, and potential adverse effects. In addition, some medications have potential benefits that extend beyond glucose lowering. These include beneficial effects on the adverse metabolic consequences of insulin resistance and possibly beta-cell preservation. Thiazolidinediones should be considered as early as possible in the natural history of type 2 diabetes because of their persistent glucose-lowering effect and their ability to reduce insulin resistance as well as because these agents may preserve beta-cell function and reverse some of the adverse metabolic consequences of insulin resistance.