Organ protection in the secondary prevention of type 2 diabetes

The placebo-controlled Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) is the only study of secondary prevention in patients with type 2 diabetes to have shown a benefit. While treatment with pioglitazone did not significantly reduce the primary composite endpoint, it did significantly lower the incidence of many of its components, including all-cause mortality, nonfatal myocardial infarction (including silent infarctions), stroke, acute coronary syndrome and limb amputation. Pioglitazone also reduced the relative risk of the combined endpoint of death, myocardial infarction and stroke by 16% compared to placebo. In the subgroup of patients with myocardial infarction, the risk of myocardial infarction and acute coronary syndromes was reduced with the active treatment, which also substantially reduced (-47%) the risk of stroke in patients with prior stroke. Pioglitazone has furthermore demonstrated numerous antiatherogenic effects in clinical and preclinical investigations.