September 4, 2006

Takeda Pharmaceuticals North America
Takeda Pharmaceutical Company Limited

New Analyses Show ACTOS®(pioglitazone HCl) Reduced Risk of Secondary Stroke by Almost 50 Percent in High Risk Type 2 Diabetes Patients^1,2

Barcelona, Spain, September 3, 2006 --- Results of new analyses³ found that ACTOS®(pioglitazone HCl), an oral antidiabetic medication,⁴ significantly reduced the risk of recurrent stroke in high-risk patients with type 2 diabetes.⁵ The findings were presented today in a late-breaker session at the World Congress of Cardiology in Barcelona.

"These results are very encouraging news for people with type 2 diabetes because they demonstrated that ACTOS reduced the incidence of strokes in patients who had already experienced a stroke from 10.2 percent down to 5.6 percent, translating to a risk reduction of almost 50 percent," said Robert Wilcox, M.D., professor in the Department of Cardiovascular Medicine at Queen's Medical Centre, University Hospital, Nottingham, United Kingdom.

These new analyses from the landmark PROactive Study examined the effects of ACTOS on the risk of stroke and other cardiovascular (CV) outcomes in high-risk patients with type 2 diabetes with and without prior stroke.^6/ Pre-specified study endpoints included all-stroke and CV disease death, myocardial infarction (MI, excluding silent MI) or stroke.⁷

According to the results, there were statistically significant benefits of ACTOS in patients who had suffered a prior stroke.⁸ The incidence of recurrent stroke was reduced by 47 percent (P=0.008)⁹ and the combined risk of death, MI or stroke was reduced by 28 percent (P<0.05).¹⁰ There was no effect of ACTOS on subsequent strokes in patients who had never experienced a stroke. ¹¹
Patients with diabetes are at an increased risk of stroke.¹² In fact, the risk is two to four times higher for people with diabetes than the general population.¹³ Results from the PROactive Study demonstrated that an oral glucose-lowering medi-cation could substantially impact the risk of some CV events, including the combined risk of death, MI and stroke in high-risk patients with type 2 diabetes.¹⁴

Notes to Editors

About the PROactive Study

PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events)was a landmark study that prospectively looked at the impact in total mortality and macro-vascular morbidity using ACTOS, a glucose-lowering agent.^15,16 It was a randomized, double-blind, placebo-controlled outcome study of 5,238 patients with type 2 diabetes and macrovascular disease.^17,18,19 Patients were randomized to receive either ACTOS or placebo in addition to standard-of-care treatment²⁰ (including the routine use of anti-hypertensives such as ACE inhibitors and beta blockers; glucose-lowering agents such as metformin, sulfonylureas and insulin; antiplatelet drugs such as aspirin, and lipid-modifying medicines such as statins and fibrates).²¹

This study focused on two key endpoints: a primary combination endpoint of seven different macrovascular events including both disease and procedural endpoints;²² and a principal secondary combination endpoint of death, heart attack and stroke.²³

As reported at the European Association for the Study of Diabetes (EASD) Annual Meeting in September 2005, the primary endpoint was reduced by 10 percent but had not reached statistical significance by study end (P=0.095).²⁴ The principal secondary endpoint showed that ACTOS significantly reduced the combined risk of heart attacks, strokes and death by 16 percent (P=0.027)²⁵ in high-risk patients with type 2 diabetes.²⁶

About ACTOS

Takeda is the originator of thiazolidinedione derivatives and Actos® is a member of the thiazolidinedione class of "insulin-sensitizing" agents. Insulin sensitizers help improve the body's ability to effectively use its own insulin by reducing insulin resistance --- a defect that has been identified as a possible cause of type 2 diabetes.

In the United States, Takeda Pharmaceuticals North America, Inc. (TPNA), the U.S. marketing subsidiary wholly owned by Takeda, launched Actos® in August 1999. In Japan, Takeda launched Actos® in December 1999 and received the approval of marketing authorization in European Union in October 2000.
Actos® is now being marketed in approximately 70 countries by Takeda group companies and also by a worldwide partner for Actos®, Eli Lilly and Company, and other licensees.

-Ends-

1 1Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

2 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

3 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

4 ACTOS Prescribing Information. Last updated August 2004.

5 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

6 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

7 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

8 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

9 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

10 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

11 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

12 Wilcox R, Bousser M, Dormandy J. Effects of Pioglitazone in Stroke Prevention in Type 2 Diabetes: A Prespecified Subgroup Analysis of PROactive. Abstract. World Congress of Cardiology 2006.

13 American Diabetes Association. Complications of Diabetes in the United States page.
Available at:
Accessed July 17, 2006.

14 Charbonnel E, Dormandy J, Erdmann E, Massi-Benedetti M. PROactive Study:
PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study In Type 2 Diabetic Patients Comparing Pioglitazone With Placebo In Addition To Existing Therapy. PowerPoint Presentation presented at 41st European Association for the Study of Diabetes Annual Meeting. 2005.

15 Charbonnel E, Dormandy J, Erdmann E, Massi-Benedetti M. PROactive Study:
PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study In Type 2 Diabetic Patients Comparing Pioglitazone With Placebo In Addition To Existing Therapy. PowerPoint Presentation presented at 41st European Association for the Study of Diabetes Annual Meeting. 2005.

16 ACTOS Prescribing Information. Last updated August 2004.

17 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

18 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

19 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

20 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

21 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

22 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

23 Dormandy J, Charbonnel B, Eckland D, et al. 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.
The Lancet. 2005;366:1279-1289.

24 Charbonnel E, Dormandy J, Erdmann E, Massi-Benedetti M. PROactive Study:
PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study In Type 2 Diabetic Patients Comparing Pioglitazone With Placebo In Addition To Existing Therapy. PowerPoint Presentation presented at 41st European Association for the Study of Diabetes Annual Meeting. 2005.

25 Charbonnel E, Dormandy J, Erdmann E, Massi-Benedetti M. PROactive Study:
PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study In Type 2 Diabetic Patients Comparing Pioglitazone With Placebo In Addition To Existing Therapy. PowerPoint Presentation presented at 41st European Association for the Study of Diabetes Annual Meeting. 2005.

26 Charbonnel E, Dormandy J, Erdmann E, Massi-Benedetti M. PROactive Study:
PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study In Type 2 Diabetic Patients Comparing Pioglitazone With Placebo In Addition To Existing Therapy. PowerPoint Presentation presented at 41st European Association for the Study of Diabetes Annual Meeting. 2005.

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