Diabetes News
ATHENS, Greece, September 12 (PRNewswire) — Data From the PROactive Study Presented at the 41st Annual Meeting of the European Association for the Study of Diabetes (EASD), 10-15 September 2005
Actos(r) (pioglitazone) significantly reduces the combined risk of death, stroke or heart attack by 16% in high-risk patients with Type 2 diabetes who were already receiving optimised standard of care, the landmark PROactive study revealed today.
"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 or death in high-risk patients." said Professor John Dormandy, Professor of Vascular Sciences at St. George's Hospital, London, UK, and chairman of the PROactive Steering Committee. "This groundbreaking study gives new hope to people with Type 2 diabetes who, despite their attempt to control blood glucose and take medications, fear these life-threatening events."
Professor Dormandy added "Until we know how pioglitazone works to provide these life-saving benefits, the beneficial results of PROactive should not be generalised to any other oral glucose-lowering medication."
These long-awaited results from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) outcome study,(1) an international, prospective, double-blind, randomised controlled study, were presented today at the 41st Annual Meeting of the European Association for the Study of Diabetes (EASD). PROactive was designed to determine the effects of pioglitazone on mortality and morbidity associated with cardiovascular disease progression in high-risk patients with Type 2 diabetes who had their treatment optimised during the study according to International Diabetes Federation (Europe) Guidelines. This included the appropriate use of anti-hypertensives, anti-platelet drugs, lipid-modifying medicines and glucose-lowering agents, including insulin (combined use of pioglitazone and insulin is currently contraindicated in the UK).
Compelling study results
The results presented at the EASD focused on two key endpoints: a primary combination endpoint of seven different macrovascular events(x) of varying clinical importance; and a principal secondary combination endpoint of the most serious events, namely death, stroke and heart attack. The primary endpoint was reduced by 10% but had not reached statistical significance by study end (p=0.095). The principal secondary combination endpoint showed that pioglitazone significantly reduced the risk of death, stroke or heart attack by 16% (p=0.027). In these people, the study showed that pioglitazone could prevent 21 deaths, strokes or heart attacks per 1000 patients over a 3-year period.
Other secondary endpoints include the individual components of the primary endpoint and cardiovascular mortality.
Professor John Betteridge, Professor of Endocrinology and Metabolism at University College, London, and the UK Lead Investigator for PROactive said: "These are exciting results, which should influence the management of Type 2 diabetes in the UK. Notably, these benefits were over and above those achieved with optimised standard care and, as a result, I would expect pioglitazone to be considered for many high-risk people with Type 2 diabetes"
As expected, pioglitazone (up to the maximum dose of 45 mg once daily) in addition to optimised standard therapy had a significant beneficial and sustained effect on glycaemic control (HbA1c). Pioglitazone up to the maximum dose of 45 mg once daily also demonstrated a beneficial effect on diabetic dyslipidaemia and blood pressure, which is consistent with previous clinical studies with this agent(2).
The PROactive study was also designed to examine the safety of pioglitazone in this high-risk patient group. When added to optimised standard treatment, pioglitazone up to the maximum dose of 45 mg once daily was well tolerated with a similar number of adverse events being seen in each treatment group. These were consistent with the safety profile in the approved label(3).
The PROactive trial involved 5,328 patients from 19 countries. Patients enrolled in the study had been diagnosed with Type 2 diabetes for a mean of 9.5 years and all were at increased risk of macrovascular disease. Patients were followed up for at least 30 months.
Pioglitazone is currently licensed in the UK as monotherapy in patients with Type 2 diabetes mellitus who are inadequately controlled by diet and exercise and for whom metformin is inappropriate. Pioglitazone is also licensed as part of a combination treatment in patients with insufficient glycaemic control despite maximal tolerated doses of oral monotherapy with either metformin or sulphonylurea.