Metformin will celebrate 50 years of clinical use in 2007. Pioglitazone was introduced into clinical practice in 1999. Both metformin and pioglitazone have positive effects on components of the metabolic syndrome, namely: insulin resistance, hyperinsulinaemia, visceral obesity, hyperglycaemia, dyslipidaemia and hypertension and risk factors involved in endothelial dysfunction, inflammation and atherosclerosis. Improvements in cardiovascular outcomes have been demonstrated in patients at high risk of macrovascular events with pioglitazone (PROactive) and in overweight patients with metformin (UKPDS 34). Pioglitazone may also help to sustain beta-cell function. Introduction of combination therapy using two differently acting oral antidiabetic agents at the time of diagnosis or early thereafter is becoming increasingly common in order to reach glycaemic targets (e.g. HbA1C ≤7.0%). The combination of metformin and pioglitazone in an early stage of type 2 diabetes enables greater likelihood that these targets can be with insulin secretagogues. attained without the risk of hypoglycaemia associated with insulin secretagogues