New Data Showed ACTOS(R) (pioglitazone HCl) Prevented Progression Of Atherosclerotic Plaque Volume In Patients With Type 2 Diabetes

New data from a clinical trial using
intravascular ultrasound (IVUS) technology found that in patients living
with type 2 diabetes, ACTOS(R) (pioglitazone HCl) reduced the
atherosclerotic burden in the coronary arteries compared to glimepiride,
and prevented progression compared to baseline. These data stem from the
PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic
Coronary Obstruction Prospective Evaluation) trial.


The PERISCOPE trial was presented as a late breaker at the 57th
Annual Scientific Session of the American College of Cardiology in Chicago.
This trial adds to the body of cardiovascular data for ACTOS. ACTOS
studies, conducted over the past 10 years in more than 16,000 patients,
including short- and long-term trials, as well as prospective and
observational studies, have shown no evidence that ACTOS is associated with
an increased risk of heart attack, stroke, or death.



"We are pleased with the results of the PERISCOPE, which further
expands our cardiovascular data with ACTOS," said David P. Recker, M.D.,
senior vice president, Clinical Sciences and interim president at Takeda
Global Research & Development. "While not definitive, data from PERISCOPE
combined with results from a previous study, looking at surrogate
endpoints, have shown a consistent trend toward decreasing cardiovascular
risk by reducing the atherosclerotic burden in people with type 2
diabetes."



PERISCOPE is the first clinical trial to examine the effects of an oral
antidiabetic medication on the development of coronary atherosclerosis in
patients with type 2 diabetes using IVUS technology. The trial conducted in
97 centers in the U.S., Canada and Latin America with 543 patients, used
IVUS imaging of the coronary arteries. The analysis demonstrated a
statistically significant difference in percent change in coronary artery
atheroma volume in favor of ACTOS treatment compared to glimepiride
treatment.



The data showed that patients treated with glimepiride, a sulfonylurea
and commonly used diabetes medication, exhibited progression of coronary
atherosclerosis. In contrast, the ACTOS arm showed no progression of
coronary atherosclerosis over the 18-month period from the initial baseline
measurement.



Cardiovascular safety data was collected by looking at macrovascular
events and episodes of congestive heart failure (CHF). The number of
episodes of a common cardiovascular endpoint of cardiovascular mortality,
non-fatal MI, or non-fatal stroke was 6 (2.2%) in glimepiride patients and
5 (1.9%) in ACTOS-treated patients. The number of hospitalizations due to
CHF was equivalent in both arms. In the ACTOS-treated group, eight patients
experienced a bone fracture, none involving the hip or spine.
















Atherosclerosis is a condition that leads to reduced or blocked blood
flow, and is accelerated in patients with type 2 diabetes. Atherosclerosis-
related cardiovascular disease is the leading cause of death and disability
in people with type 2 diabetes. Published data shows that slowed
progression and reductions in atheroma volume lessens the incidence of a
second heart attack. IVUS measures the volume of plaque build-up in the
coronary arteries, a marker of coronary atherosclerosis.



The data are consistent with the findings of the CHICAGO (Carotid
intima- media tHICkness in Atherosclerosis using pioGlitazOne) trial. Both
PERISCOPE and CHICAGO support the findings of the PROactive (PROspective
PioglitAzone Clinical Trial In MacroVascular Events) trial, which showed
that ACTOS was not associated with an increased risk of heart attack,
stroke or death.



The CHICAGO Study



The CHICAGO trial was an 18-month, multicenter, randomized study that
enrolled 462 patients with type 2 diabetes, all from the Chicago area. The
primary goal was to compare the effects of ACTOS versus glimepiride, a
sulfonylurea, on carotid intima-media thickness (CIMT), defined as the
thickness of the inner lining of a patient's neck arteries. CIMT is an
established surrogate marker of atherosclerosis. The CHICAGO analysis
demonstrated a similar result on the progression of atherosclerosis as was
observed in PERISCOPE.



The PROactive Study



The PROactive study was a prospective, randomized, placebo-controlled
outcomes trial. The study included 5,238 patients with type 2 diabetes and
a history of macrovascular disease, who were force-titrated up to 45 mg
daily of either ACTOS or placebo in addition to standard of care. In this
study, there was no difference in the number of macrovascular events
between standard of care and ACTOS, and standard of care alone. Although
there was no statistically significant difference between ACTOS and
standard of care for the primary endpoint, there was no increase in
mortality or total macrovascular events with ACTOS. In 2007, the ACTOS
Prescribing Information was revised by the U.S. Food and Drug
Administration to include this reassuring cardiovascular safety data.



About ACTOS



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, a prescription medication, 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.



Important Safety Information About ACTOS(R) (pioglitazone HCl)



ACTOS is not for everyone. Certain patients with heart failure should
not start taking ACTOS. ACTOS can cause or worsen congestive heart failure.
Talk to your doctor immediately if you experience rapid weight gain, fluid
retention, or shortness of breath.



Do not take ACTOS if you have active liver disease. Your doctor should
perform a blood test to check for liver problems before you start ACTOS and
periodically thereafter. 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 flulike symptoms, mild-to-moderate
swelling of legs and ankles, and anemia. Some people, particularly women,
are at higher risk of having bone fractures while taking ACTOS. When taking
ACTOS with insulin or sulfonylureas, you may be at risk for low blood
sugar. Patients with diabetes should have regular eye exams. If you
experience vision problems, consult your doctor immediately. Very rarely,
some patients have experienced visual changes while taking ACTOS.



Please visit the ACTOS Web site at actos for Complete
Prescribing Information.



Takeda Global Research & Development Center, Inc.



Based in Deerfield, Ill., and London, U.K., Takeda Global Research &
Development Center, Inc. is a wholly owned subsidiary of Takeda
Pharmaceutical Company Limited, the largest pharmaceutical company in
Japan. Takeda Global Research & Development was established in 2004 and is
responsible for Takeda's clinical research and development in the U.S. and
Europe, supporting clinical and product development activity for Takeda
commercial organizations in the U.S. - Takeda Pharmaceuticals North
America, Inc, and in Europe: six sales and marketing companies,
respectively. With a robust pipeline of compounds in development for
diabetes, cardiovascular disease and other conditions, Takeda rapidly
brings innovative products to market to improve patient health and enhance
the practice of medicine. To learn more about the company, visit
tgrd.


Takeda Global Research & Development Center, Inc.

tgrd


View drug information on ACTOS.