Antidiabetic Agent Proves It Can Slow Plaque
Build-Up in Coronary Arteries
Thiazolidineddiones drug pioglitzsone (Actos) beats
sulfonyhlureas drug glimepiride (Amaryl)
March 31, 2008 – A new study has found the
medication pioglitzone – from a newer class of antidiabetic agents – is more
effective than glimepiride in slowing the development of plaque in the
coronary arteries of diabetics. More importantly, the researchers say it
is the first demonstration of the ability of any hypoglycemic agent to
slow the progression of coronary atherosclerosis in patients with
diabetes.
Thiazolidinediones medications (including rosiglitazone
(Avandia)
produced a significantly increased risk of heart attack, congestive
heart failure and death
It’s potentially critical information for the more
than 20 million Americans – primarily older people - with diabetes,
because so many die from cardiovascular disease.
Atherosclerosis (process in which plaque builds up
in the inner lining of the arteries) in patients with diabetes is
particularly aggressive, characterized by higher cardiovascular event
rates. Cardiovascular disease is the cause of death in approximately 75
percent of patients with diabetes. Determining the optimal treatment for
coronary artery disease for patients with diabetes has important public
health implications, according to information in the article.
This study, to be published in the April 2 issue of
the Journal of the American Medical Association, is being released early
online today to coincide with its presentation at the annual conference
of the American College of Cardiology.
There has been little existing evidence to support
a preference of one class of glucose-lowering medication over any other
as a means to reduce the severity of atherosclerotic disease.
Sulfonylureas, such as glimepiride, have been
available for decades and represent one of the most commonly-used
classes of antidiabetic therapy.
Thiazolidinediones (TZDs; such as pioglitazone) are
a relatively new class of antidiabetic agents.
About Pioglitazone
Pioglitazone, brand name Actos) is used with a diet and exercise
program and sometimes with other medications, to treat type 2 diabetes
(condition in which the body does not use insulin normally and therefore
cannot control the amount of sugar in the blood).
Pioglitazone is in a class of medications called
thiazolidinediones. It works by increasing the body's sensitivity to
insulin, a natural substance that helps control blood sugar levels.
Pioglitazone is not used to treat type 1 diabetes
(condition in which the body does not produce insulin and, therefore,
cannot control the amount of sugar in the blood) or diabetic
ketoacidosis (a serious condition that may develop if high blood sugar
is not treated).
Glimepiride, brand name Amaryl, is used with diet and exercise to treat
type 2 diabetes (condition in which the body does not use insulin
normally and therefore cannot control the amount of sugar in the blood).
Glimepiride stimulates your pancreas to make more
insulin and also makes your body more sensitive to insulin. Glimepiride
may be used with or without insulin.
This medication is sometimes prescribed for other
uses; ask your doctor or pharmacist for more information.
Glimepiride comes as a tablet to take by mouth. It
is usually taken once a day. The tablet should be taken with breakfast
or the first big meal of the day. Follow the directions on your
prescription label carefully, and ask your doctor or pharmacist to
explain any part you do not understand. Take glimepiride exactly as
directed. Do not take more or less of it or take it more often than
prescribed by your doctor.
Continue to take glimepiride even if you feel well.
Do not stop taking glimepiride without talking to your doctor.
Steven E. Nissen, M.D., of the Cleveland Clinic,
and colleagues conducted the PERISCOPE trial to directly compare the
effectiveness of two alternative approaches for treating hyperglycemia,
an insulin-providing strategy (glimepiride) vs. an insulin-sensitizing
strategy (pioglitazone), in reducing progression of atherosclerosis in
543 patients with type 2 diabetes and coronary disease.
The randomized, multicenter trial included 97
academic and community hospitals in North and South America (enrollment
August 2003 - March 2006).
The patients underwent coronary intravascular
ultrasonography to measure progression of atherosclerosis and were
randomized to receive glimepiride or pioglitazone for 18 months.
Atherosclerosis progression was measured by the change in percent
atheroma volume (PAV; a measurement of plaque build-up in an artery)
with repeat intravascular ultrasonography examination in 360 patients at
study completion.
The primary efficacy measure, change in PAV,
increased 0.73 percent in the glimepiride group and decreased 0.16
percent in the pioglitazone group.
An alternative analysis imputing values for
patients who did not have follow-up ultrasound procedures and based on
baseline characteristics showed an increase in PAV of 0.64 percent for
glimepiride and a decrease of 0.06 percent for pioglitazone.
A secondary efficacy measure, change in maximum
atheroma thickness increased in the glimepiride group and decreased in
the pioglitazone group.
“The observation of a significant benefit for
pioglitazone treatment represents, to our knowledge, the first
demonstration of the ability of any hypoglycemic agent to slow the
progression of coronary atherosclerosis in patients with diabetes.
Evidence for a slowing of disease progression has proven a very
challenging end point in recent years with the prominent failure of
several promising approaches,” the authors write.
“Patients randomized to pioglitazone exhibited a
lower rate of progression of coronary atherosclerosis across a wide
array of prespecified and exploratory subgroups.
“These finding may have important implications for
defining the optimal strategy for management of patients with type 2
diabetes and coronary atherosclerosis,” the researchers conclude.
Editorial: Does periscope provide a new perspective
on diabetic treatment?
An editorial in the same issue states, “The results
of the PERISCOPE trial, even though they relate to a surrogate end
point, are consistent with the modest clinical benefit demonstrated for
the prevention of coronary events with pioglitazone, within PROACTIVE
and other trials.
“However all glitazones share a common adverse
effect on heart failure, and other noncardiovascular adverse effects,
such as bone fractures. …
“Overall, in the current context of concerns
regarding the cardiovascular safety of glucose lowering and regardless
of the mechanisms involved, PERISCOPE provides a reassuring perspective
for patients with type 2 diabetes and high cardiovascular risk.”
The editorial was written by Philippe Gabriel Steg,
M.D., of the Centre Hospitalier Bichat-Claude Bernard, Paris, and
Editor, JAMA-français, and Michel Marre, M.D., Université Paris VII
Faculté de Médecine X Bichat, Paris, comment on the findings of Dr.
Nissen and colleagues.
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