Pioglitazone improves the lipid profile as well as lowering blood glucose levels and increasing insulin sensitivity, and hence the drug could have beneficial effects on atherosclerosis. People with type 2 diabetes at high risk of cardiovascular events will already be taking a statin, antihypertensives, and aspirin. The PROactive study examined the effect of adding pioglitazone to such therapy. It was well designed, apart from a primary end-point that was a mixture of actual events (myocardial infarction (MI), stroke, allcause mortality) and therapeutic procedures such as coronary stenting.
The primary end-point was not statistically different in those given active treatment or placebo, although a widening gap appeared to be developing by the end of the study. The main secondary end-point of allcause mortality,MI, and stroke was reached in 11.5% of patients on pioglitazone and 13.5% on placebo, and this was statistically significant. However, if a doctor offered their patient an additional tablet that would change risk of problems over three years from about 13% to about 12%, and may cause weight gain (4kg) and ankle swelling, the patient might not be tempted.