SOURCE: Takeda Pharmaceuticals

June 11, 2005 13:00 ET

New Study Demonstrated Add-On Effects of ACTOS® (Pioglitazone HCl) for Patients With Type 2 Diabetes Taking a Statin

Conversion Trial Studied the Effect of ACTOS on Diabetic Dyslipidemia Compared to Avandia® (Rosiglitazone Maleate)

SAN DIEGO, CA -- (MARKET WIRE) -- June 11, 2005 -- A new study has shown that people with type 2 diabetes on statin therapy for diabetic dyslipidemia who were switched to the oral anti-diabetic drug ACTOS from Avandia saw significant improvements, beyond those resulting from traditional cholesterol-lowering statin therapy, in key lipid parameters. These effects were independent of blood glucose control, which remained stable after the therapies were changed. The study, named COMPLEMENT, was presented today at the American Diabetes Association (ADA) 65th Annual Scientific Sessions.

"These data suggest that people with type 2 diabetes on a statin who switch from Avandia to ACTOS may realize incremental benefits to their lipid levels," said Robert Spanheimer, M.D., medical director for diabetes and metabolism at Takeda Pharmaceuticals North America. "Additionally, these results build on the growing body of evidence that ACTOS can confer benefits beyond blood glucose reduction: it can increase HDL and lower triglycerides. Low HDL cholesterol and elevated triglycerides represent cardiovascular risk factors for patients with type 2 diabetes."

Diabetic dyslipidemia, a risk factor for cardiovascular disease, is a profile of lipid abnormalities typically seen in people with type 2 diabetes. The pattern consists of elevated triglycerides, reduced levels of HDL cholesterol, normal or slightly elevated levels of total and LDL cholesterol, and a shift toward smaller and denser LDL cholesterol particles. While dyslipidemia (irregularity of the lipid profile) also occurs in people who do not have diabetes, the specific abnormalities in the lipoprotein pattern characteristic of diabetic dyslipidemia appear to add excess risk for people with diabetes.

"What is unique about diabetic dyslipidemia is that lipid profiles may show normal levels of LDL, yet lower HDL and increased triglycerides that single lipid therapy alone may not address," noted Dr. Spanheimer.

Study Background and Design

Previously reported results from a head-to-head, randomized, controlled study showed that ACTOS significantly improved lipid levels to a greater extent than Avandia. COMPLEMENT was designed to determine whether these effects would remain if patients were on a statin -- currently a recommended therapy for people with diabetic dyslipidemia -- in addition to ACTOS or Avandia. ACTOS and Avandia are members of a class of drugs called thiazolidinediones (TZDs) that reduce blood glucose levels by targeting insulin resistance, a core metabolic dysfunction of type 2 diabetes.

The multicenter, single-arm, 17-week, open-label study enrolled 305 people with type 2 diabetes taking statins (with or without other lipid-lowering drugs) along with Avandia alone or in combination with another oral anti-diabetic drug. Patients were then switched to ACTOS (30 mg QD, titrated to 45 mg QD at investigator discretion), while maintaining their statin with or without other lipid-lowering therapy. Blood glucose and lipid levels (including fasting triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol) were measured at the start of the study when patients were on Avandia, and during the time the patients were on ACTOS.

Results

The results, which were presented in the form of several abstracts at the ADA meeting, showed ACTOS significantly lowered lipid levels when patients were switched from Avandia. Additionally, the effects were seen regardless of age or gender, or if patients took fenofibrate in addition to statin therapy. These improvements were consistent with those observed in the previous head-to-head study. Specifically:

--  Triglycerides were reduced by nearly 21 percent (P < 0.0001), total
    cholesterol was reduced by 10.5 percent (P < 0.0001),
    
--  LDL-C decreased by 1.1 percent (P=0.040),
    
--  HDL-C: Mean HDL particle concentration increased 3.8 µmol/L, and mean
    levels of Apo A1, a component necessary for HDL-C metabolism and
    biosynthesis, increased by 9.7 mg/dL.
    
--  LDL/VLDL: Mean LDL particle size increased 0.23 nm and mean LDL
    particle concentration decreased 189 nmol/L, indicating there were fewer
    LDL particles and they were larger and more buoyant without an increase in
    LDL.  Mean VLDL particle concentration decreased 44.9 nmol/L. Additionally,
    mean levels of Apo B, a component of atherogenic lipoproteins, including
    LDL and VLDL-C, decreased by 2.6 mg/dL.
    
"These changes in the particle size and composition of good and bad cholesterol particles are quite interesting," continued Dr. Spanheimer. "In patients with type 2 diabetes, a lipid profile characterized by higher levels of large, more buoyant LDL particles may provide less risk than a profile characterized by smaller, dense LDL particles."

About ACTOS® (pioglitazone HCl)

ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.

Additional Information

ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor 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 ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.

Do not take ACTOS 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 as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood glucose.

Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and 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. Additional information about Lilly is available on www.lilly.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 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, sleep, 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.

ACTOS® (pioglitazone HCl) is a registered trademark of Takeda Pharmaceutical Company, Limited and used under license by Takeda Pharmaceuticals North America, Inc. and Eli Lilly and Company. Please visit the ACTOS Web site at www.actos.com for complete Prescribing Information.

Abstract #s: 553-P, 2137-PO, 555-P, 2139-PO, 2140-PO, 2143-PO, 2141-PO, 2142-PO

Contact Information

  • Contacts:
    Jocelyn M. Gerst
    Takeda Pharmaceuticals North America
    847-769-6889 (cell)
    847-383-3696 (office)

    Amy Losak
    Ketchum
    917-865-6688 (cell)