ACTOS is Now Most Prescribed Insulin Sensitizer by Endocrinologists; Most Recent Thiazolidinedione (TZD) is the Fastest Growing Product in its Market.

Business Editors/Health & Medical Writers

LINCOLNSHIRE, Ill.--(BUSINESS WIRE)--April 7, 2000

ACTOS(R) (pioglitazone hydrochloride), which is distributed by Takeda Pharmaceuticals America, Inc. and co-promoted with Eli Lilly and Company, has been the leading thiazolidinedione (TZD) for new prescriptions written by endocrinologists since February 25, 2000, according to IMS Health data.

TZDs are a preferred therapy option for reducing insulin resistance, an underlying cause of type 2 diabetes.

"It is important to see that the experts in diabetes care, endocrinologists, are choosing ACTOS for their patients who require an insulin sensitizing therapy," said William Wishner, M.D., Associate Director, External Medical Affairs.

In addition to being the leader among endocrinologists, IMS Health data also show that ACTOS has been the fastest growing product in the TZD market by all measurements, including total prescriptions, total prescription market share, new prescriptions and new prescription market share, since September 1999.

While 0.4% of U.S. physicians are endocrinologists, they account for approximately 12% of total TZD prescriptions written in the U.S.

"We believe that physicians are beginning to really understand the benefits of ACTOS, which should also be helpful to patients transitioning from Rezulin(R) (troglitazone)," said Wishner.

ACTOS has a broad line of indications and is always taken once daily, regardless of dosage strength and meal schedule. As an adjunct to diet and exercise, ACTOS is approved for use as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.

In 1999, Rezulin was prescribed for use with insulin 40 percent of the time and with a sulfonylurea 43 percent of the time. ACTOS is FDA approved for use with these two therapies.

Additionally, ACTOS has shown effect in helping to improve the most common lipid (blood fat) imbalance found in patients with type 2 diabetes. Patients with type 2 diabetes often have high triglyceride levels and low levels of HDL, or "good" cholesterol. These two abnormalities increase the risk for heart disease, especially in patients with diabetes.

In clinical trials, compared with placebo, ACTOS significantly decreased mean triglyceride levels and increased mean HDL levels in both monotherapy and in combination with sulfonylureas, metformin or insulin. In contrast, no significant change in mean total cholesterol or mean LDL or "bad" cholesterol levels was seen with ACTOS used either as monotherapy or in combination therapy.

There have been no reported cases of jaundice or liver failure associated with ACTOS use in U.S. placebo-controlled clinical trials.

However, since liver toxicity has been observed with the earliest-approved drug in the TZD class, patients should obtain medical monitoring of liver enzyme levels (via a blood test) prior to the start of therapy, every two months for the first year of therapy, and periodically thereafter. ACTOS should not be initiated in patients exhibiting clinical evidence of active liver disease.

Therapy with ACTOS, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. As a result, these patients may be at risk for pregnancy while taking ACTOS and adequate contraception should be recommended. Administration of oral contraceptives has not been fully evaluated in patients being treated with ACTOS.

Therefore, additional caution regarding co-administration of ACTOS and an oral contraceptive should be exercised.

ACTOS is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. The majority of side effects reported during ACTOS clinical trials were mild. Those most commonly reported included symptoms of upper respiratory tract infection, headache, sinusitis, muscle pain, tooth disorder and sore throat.

As observed with other members of this class of drugs, weight gain has been noted. Additionally, mild to moderate edema and anemia have been reported in patients taking ACTOS. ACTOS should be used with caution in patients with edema.

Patients receiving ACTOS in combination with insulin or sulfonylureas may be at risk for hypoglycemia, and a reduction in the dose of insulin or sulfonylureas may be necessary. Occasionally, blood sugar levels increased during clinical trials.

Takeda America Research and Development Center, Inc. and Takeda Pharmaceuticals America, Inc. are wholly owned subsidiaries of Takeda Chemicals Industries, Ltd., a global pharmaceutical company based in Japan. Takeda America Research and Development Center is the research and development subsidiary based in Princeton, N.J. Takeda Pharmaceuticals America is based in Lincolnshire, IL.

Internationally recognized as a leader in research and development, Takeda focuses on treatments for diabetes, cardiovascular and allergic disease, bone and joint disease and central nervous system disorders.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.

For further information on ACTOS, visit www.actos.com. To obtain a faxed copy of complete prescribing information, call 800/753-0352 x728. For company information, visit Takeda Pharmaceuticals America's Web site at www.takedapharm.com.

Rezulin(R) is a registered trademark of Warner-Lambert.