Type 2 diabetes is a common disease associated with an increased risk of long-term complications, in particular cardiovascular disease. Intervention trials have provided evidence that strict metabolic control can substantially reduce the burden of the disease. However, in order to accomplish this, the pathogenetic defects must be tackled by appropriate therapy. Insulin resistance is a common defect in these patients and it is even more severe in those who are obese. Insulin resistance not only contributes to impaired glucose homeostasis, but also to the development of dyslipidaemia, hypertension, inflammatory response and endothelial dysfunction, thus exacerbating the cardiovascular risk. Improvement of insulin sensitivity can be obtained with metformin and thiazolidinediones. These drugs act through different mechanisms with metformin exerting a prevalent effect on the liver and glitazones improving insulin sensitivity in peripheral tissue. Because of different mechanisms, the association of the two compounds is likely to result in an additive effect. Clinical trials available indicate that the combination of the two drugs results in greater improvement in plasma glucose concentration and HbA(1c) as compared to single therapy, without increasing the occurrence of specific side effects. More recently, the two compounds have been associated in the same tablet, thus providing the opportunity for a more convenient treatment that may encourage patient compliance and, at the same time, provide a tool to assess whether a more aggressive intervention on insulin resistance may produce favourable effects on the cardiovascular risk.