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ACTOplus met™ (pioglitazone HCl and metformin HCl) Approved by the FDA for Type 2 Diabetes

August 29, 2005
New product combines two widely used diabetes medications in a single tablet, offering patients a convenient option

LINCOLNSHIRE, Ill., August 29, 2005 – Takeda Pharmaceuticals North America, Inc. (TPNA) today announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for ACTOplus met™ for the treatment of type 2 diabetes. This is the second Takeda product approved in the U.S. this summer, following the approval of ROZEREM™ (ramelteon) on July 22, 2005.

ACTOplus met combines ACTOS® (pioglitazone HCl) and metformin, two widely used diabetes medications, in a single tablet. ACTOS directly targets insulin resistance, a condition where the body does not efficiently use the insulin it produces, and metformin acts primarily by reducing the amount of glucose produced by the liver. These medications work in combination to help patients with type 2 diabetes manage their blood glucose levels.

To offer physicians greater flexibility in treating their patient’s needs, ACTOplus met will be available in two dosages of pioglitazone/metformin – 15 mg/500 mg and 15 mg/850 mg – both of which are to be given once a day or in divided doses not exceeding the maximum recommended daily doses of pioglitazone 45 mg and metformin 2,550 mg as mentioned in the approved labeling.

“To reach target blood glucose levels, many people with type 2 diabetes will have to take a combination of therapies. In fact, within three years of being prescribed their first medication, approximately 50 percent of patients will need to add additional therapies to manage their condition,” said Ralph DeFronzo, M.D., professor of Medicine and chief of the Diabetes Division at the University of Texas Health Science Center at San Antonio. “ACTOplus met may help patients reduce the number of pills they take each day, and offers a new and convenient treatment option.”

According to the American Diabetes Association, diabetes affects more than 18 million people, and type 2 diabetes is the most common form of the disease. Both ACTOS and metformin are widely used medications in the treatment of type 2 diabetes and both have a known safety profile. Combining these medications may provide patients with an easier way to take the two drugs, as they are already often prescribed together to help manage the disease.

Takeda Global Research & Development Center, Inc. submitted the ACTOplus met NDA in October 2004. Takeda expects the medication to be available to patients by October 2005.

“Takeda is committed to developing appropriate treatment options for healthcare providers and their patients,” said Mark Booth, president of Takeda Pharmaceuticals North America, Inc. “ACTOplus met reflects that commitment by offering a convenient option for people with type 2 diabetes and an important new addition to the ACTOS portfolio.”

About ACTOplus met & ACTOS

ACTOplus met is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of pioglitazone and metformin or whose diabetes is not adequately controlled with metformin or pioglitazone alone.

ACTOS is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. ACTOS may be used alone or in combination with metformin, sulfonylureas, or insulin.

A small number of people who have taken metformin, a component of ACTOplus met, have developed a rare, serious condition called lactic acidosis. Lactic acidosis, a buildup of lactic acid in the blood, can be fatal in about half the cases. Because lactic acidosis occurs most frequently in people with kidney problems, ACTOplus met should not be used in people with kidney disease or in people 80 years of age and older whose kidneys do not work properly. ACTOplus met should not be taken by people with metabolic acidosis, congestive heart failure requiring treatment, or with hypersensitivity to pioglitazone, metformin or any other component of ACTOplus met. ACTOplus met should not be taken by people who drink excessive amounts of alcohol. ACTOplus met should be discontinued in patients with severe infection or in patients undergoing x-ray studies using intravenous contrast dye. Talk to your health professional before discontinuing any medications.

ACTOS and ACTOplus met can cause fluid retention (swelling) that may lead to or worsen heart failure, so tell your health professional if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking either drug. If you have moderate to severe heart failure, ACTOS or ACTOplus met is not recommended. Your health professional should perform a blood test to check for liver problems before you start ACTOS or ACTOplus met and periodically thereafter. Do not take ACTOS or ACTOplus met if you have active liver disease.

Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS or ACTOplus met, as it could increase your chance of becoming pregnant.

ACTOS or ACTOplus met should not be used in patients with type 1 diabetes.

For more information, including complete prescribing information for ACTOS and ACTOplus met, talk to your pharmacist or health professional or go to www.actos.com.

Takeda Pharmaceuticals North America, Inc.

Based in Lincolnshire, Ill., Takeda Pharmaceuticals North America, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. In the United States, Takeda currently markets oral diabetes, insomnia and cholesterol-lowering treatments, and through the Takeda Global Research & Development Center, Inc., the company has a robust pipeline with compounds in development for diabetes, cardiovascular disease and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about the company and its products, visit www.tpna.com . For further information on metformin, contact your pharmacist or health provider.

ACTOS, ROZEREM and ACTOplus met are registered trademarks of Takeda Pharmaceutical Company Limited and used under license by Takeda Pharmaceuticals North America, Inc.

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