- Prescribing Advice for GPs - https://www.prescriber.org.uk -

Pioglitazone ineffective in secondary prevention

The PROactive study1 was designed to assess if pioglitazone could reduce macrovascular complications in patients with type 2 diabetes who were at high risk of fatal and non-fatal myocardial infarction (MI) and stroke.

The United Kingdom Prospective Diabetes Study2 has already demonstrated that, in obese patients, metformin reduces cardiovascular morbidity and mortality. This is the basis for placing metformin as the first line treatment of type 2 diabetes.

The PROactive study recruited over 5,000 patients, randomised them to pioglitazone or placebo and then followed them for an average duration of about 3 years. The primary endpoint was a composite of death, non-fatal MI, stroke, acute coronary syndrome, leg amputation, coronary revascularisation and revascularisation of the leg.

At the end of the study the difference between the two arms of the study for the primary endpoint was not statistically significant. Treatment with pioglitazone does not significantly reduce the likelihood of complications or death compared to placebo.

Action: Pioglitazone remains a second line treatment for diabetes. Metformin is still first-line for diabetes because it reduces cardiovascular morbidity and mortality above its blood glucose effects. Clinicians are encouraged to follow the existing prescribing formulary advice.


  1. Dormandy JA, Charbonnel B, Eckland DJ, et al, for the PROactive investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279-89
  2. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65