Establishing and maintaining control of glycaemia is a key step in the reduction of diabetic microvascular complications. By contrast, macrovascular disease which is the most important complication and shortens the lives of many people with type 2 diabetes is not reduced by glycaemic control alone. The landmark UK Prospective Diabetes Study (UKPDS) showed that intensive glycaemic management with metformin significantly reduced the risk of a range of debilitating and/or life-threatening macrovascular complications, compared with other oral agents, diet and insulin who achieved similar overall glycaemic control. The benefits observed included diabetes-related mortality (reduced by 42%, compared with diet treatment, p = 0.017), all-cause mortality (reduced by 36%, p = 0.011), myocardial infarction (reduced by 39%, p = 0.01), and any diabetes-related endpoint (reduced by 32%, p = 0.002). Other clinical and experimental studies have shown metformin to be associated with improved outcomes and support the conclusions from the UKPDS. In addition, a well-designed retrospective analysis has shown significantly lower mortality rates in patients receiving metformin compared with patients treated with sulphonylurea monotherapy. Metformin provides a greater degree of cardiovascular protection than would be expected from its antihyperglycaemic actions alone and is the first drug of choice for the treatment of type 2 diabetes unless there are contraindications in the individual patient.