Pioglitazone significantly reduces combined risk for myocardial infarction, stroke, and death by 16 percent in high-risk patients with type 2 diabetes, according to a presentation at the annual meeting of the European Association for the Study of Diabetes.

“The PROactive study is the first in the world to prospectively show that a specific oral glucose lowering medication, namely pioglitazone, can significantly improve cardiovascular outcomes by helping to delay or reduce heart attacks, strokes and death in high-risk patients,” said John Dormandy, MD, chairman of the PROactive Study Steering Committee. “This groundbreaking study gives new hope to people with type 2 diabetes who, despite their attempts to control blood glucose and take medications, fear these life-threatening events.”

PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) was a randomized, double-blind, placebo-controlled outcome study to determine the effects of pioglitazone on mortality and morbidity associated with cardiovascular disease progression in more than 5,000 high-risk patients with type 2 diabetes as add-on therapy to standard treatment.

Standard care included routine use of anti-hypertensive medication, glucose-lowering agents such as metformin, sulfonylureas and insulin, antiplatelet drugs, and lipid-modifying medicines such as statins and fibrates.

The study focused on two key endpoints: a primary combination endpoint of seven different macrovascular events of varying clinical importance and a principal secondary combination endpoint of life-threatening events including death, myocardial infarction, and stroke.

The primary endpoint was reduced by 10 percent but did not reach statistical significance by study’s end. The principal secondary endpoint of life-threatening events showed that pioglitazone significantly reduced the risk of myocardial infarctions, strokes, and death by 16 percent.

“Pioglitazone (ACTOS) has demonstrated a unique profile in earlier comparative clinical studies by providing benefits beyond glycemic control on markers of cardiovascular risk,” commented Dr. Kitazawa, a member of the board of Takeda Pharmaceutical Company, Osaka, Japan. “However, the clinical significance of these effects of pioglitazone was unknown until we knew the exciting news from the PROactive Study. Additional clinical studies are being funded by Takeda to further improve our understanding of how ACTOS enables the results we have seen in the PROactive study, specifically the reduction in risk of heart attacks, strokes and deaths.”

Professor Dormandy added, “Until we know how pioglitazone works to provide these life-saving benefits, the beneficial results of PROactive should not be generalized to any other glucose-lowering medication.”

Pioglitazone, an insulin sensitizer belonging to the thiazolidinedione class of oral anti-diabetic medications, directly targets insulin resistance. The medication is taken once daily as an adjunct to diet and exercise, and is approved for use in type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.