A study published in The Lancet shows that Takeda's Actos (pioglitazone HCl), an oral glucose lowering medication, significantly reduces the combined risk of non-fatal heart attacks, strokes and deaths by an additional 16% on top of standard medication, such as statins, fibrates, ACE inhibitors, beta blockers, other glucose-lowering medications and anti-platelet drugs, in patients with type-2 diabetes with high risk of cardiovascular disease.
This means that for every 48 patients treated with Actos over three years one major cardiovascular event or death can be prevented.
"Seeing pioglitazone improve these cardiovascular outcomes (16% relative risk reduction) is an impressive result especially as these patients were already receiving standard treatments including the use of lipid-modifying drugs, anti-hypertensives, aspirin and other glucose-lowering agents," said Professor Ian Campbell, Consultant Physician at Victoria Hospital, Edinburgh, Scotland. He further commented, "We look forward to further analyses that I understand are being submitted to scientific meetings and to reviews of the results in the medical press during the coming year."
Dr Michael George, Managing Director of the Takeda European Research and Development Center commented, "In light of these excellent results Takeda is working on preparations for a label change for Actos."
Study design and results as presented at the 41st EASD meeting in Athens on September 12th 2005 PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) was a randomised, double-blind, placebo-controlled outcome study to determine the effects of Actos on mortality and morbidity associated with cardiovascular disease progression in more than 5,000 high-risk patients with type-2 diabetes when added to their standard treatment. Standard treatment included the use of anti-hypertensives such as ACE inhibitors and beta blockers; glucose lowering agents such as metformin, sulphonylureas and insulin; antiplatelet drugs such as aspirin and lipid-modifying medicines such as statins and fibrates.
The PROactive 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 non-fatal heart attacks, strokes and deaths.
The primary endpoint was reduced by 10% but had not reached statistical significance by the end of the study (p=0.095). However, the principal secondary endpoint of life-threatening events showed that Actos significantly reduced the combined risk of non-fatal heart attacks, strokes and deaths by 16% (p=0.027).
Data from the PROactive Study were presented at the European Association for the Study of Diabetes in Athens last month.
Additional PROactive study results of Actos showed:
- HbA1c levels (a measurement of blood glucose control) were significantly reduced by 0.5% as compared to placebo (p<0.001).
- Lipid profiles significantly improved by increasing HDL cholesterol ("good" cholesterol) by 9% more than placebo (p<0.001) and reducing triglycerides (a known cardiovascular risk factor) by 13% more than placebo (p<0.001).
- The LDL/HDL cholesterol ratio ("bad" to "good" cholesterol) was significantly improved (p<0.001). A 2% increase in LDL cholesterol ("bad" cholesterol) was observed compared to placebo (p=0.003).
- Systolic blood pressure was significantly decreased (p=0.03); median change of 3 mmHg as compared to placebo.
- The PROactive study was also designed to further examine the safety of Actos in this high-risk patient group. The results demonstrated that adverse events reported in this study were consistent with the known safety profile. Known side effects of Actos, including weight gain, oedema, non-serious hypoglycaemia and heart failure, were observed more frequently in the Actos group compared to placebo group.