Actos, Avandia Increase Risk of Fractures in Women
Treated for Diabetes
If used by elderly women with type 2 diabetes for
one year, one additional fracture would occur among every 21 women
Dec. 10, 2008 The use of thiazolidinediones, a
popular class of oral diabetic drugs, for more than one year by women
with type 2 diabetes significantly reduces bone density, resulting in
the risk of fractures being doubled. The two currently available drugs
in this class are rosiglitazone, marketed as AvandiaTM by
GlaxoSmithKline, and pioglitazone, marketed as ActosTM by Takeda
Pharmaceuticals.
Thiazolidinediones medications (including rosiglitazone
(Avandia)
produced a significantly increased risk of heart attack, congestive
heart failure and death
In absolute terms, one researcher said, if
thiazolidinediones (TZDs) are used by elderly, postmenopausal women
(around 70 years) with type 2 diabetes for one year, one additional
fracture would occur among every 21 women.
Among younger women (around 56 years), use of the
drugs for one year or longer would result in one additional fracture for
every 55 women.
The new meta-analysis by researchers from the
University of East Anglia in the United Kingdom and Wake Forest
University in the United States appear online today on the Website for
the Canadian Medical Association Journal(CMAJ) and will
appear in the January 6 issue.
"We knew going into this study that there was an
association between thiazolidinediones and fracture risk, however the
magnitude of risk had not been evaluated," said Sonal Singh, M.D.,
M.P.H., an assistant professor of internal medicine and a co-researcher
for the study.
"Women with type 2 diabetes are already at an
increased risk of fractures - with a near doubling in the risk of hip
fractures - so any additional risk from thiazolidinedione therapy could
have a considerable impact on public health," said lead author Dr Yoon
Loke, of the University of East Anglia.
Latest figures show there are around 4 million
users of these drugs in the US, while in the UK there were around 2
million prescriptions for rosiglitazone and pioglitazone last year.
TZDs doubled the
risk of congestive heart failure
In the June 2007
issue of Diabetes Care, Singh and colleagues reported that TZDs
doubled the risk of congestive heart failure in patients with type 2
diabetes. They also reported in The Journal of the American Medical
Association that use of rosiglitazone was associated both with increased
heart attacks and a doubling of heart failure. In August 2008, Singh and
colleagues commented in an online editorial for Heart that, "At this
time, justification for use of thiazolidinediones is very weak to
non-existent."
"The relatively
modest benefits of thiazolidinediones must be balanced against their
significant long-term effects on bone and the cardiovascular system,"
the researchers wrote in their most recent findings.
Clinicians should
consider the updated 2008 guidelines of the American Diabetes
Association and European Association for Study of Diabetes consensus
recommendations, which do not consider thiazolidinediones among the
well-validated core therapies for type 2 diabetes and uniformly advised
against the use of rosiglitazone. (Diabetes Care, Oct. 22, 2008)
"If one assumes that half of those users were women
and that the baseline risk of fractures is similar to that found in the
ADOPT study, an estimated 30 000 excess fractures may have occurred if
these women had been prescribed thiazolidinediones rather than metformin
for more than a year," said Loke.
"The underlying causes of this gender-specific
effect of thiazolidinediones require further investigation. In the
meantime, regulatory authorities and clinicians should reconsider
recommending these drugs to women with type 2 diabetes.
"This is a problem that arises with long-term use,
and patients should not stop or change their treatment suddenly without
consulting their doctors. Women who have taken these drugs for more than
a year should speak to their doctors about other treatment options."
Recent research into thiazolidinediones has focused
on the drugs' adverse cardiovascular effects. This new meta-analysis
involved a systematic review of 10 clinical trials involving a total of
13,715 participants. The trials lasted from one to four years and all
were double-blinded.
All of the studies included participants with
impaired glucose tolerance and type 2 diabetes, and all compared the
risk of fracture among patients with type 2 diabetes who were taking TZD
therapy and patients not taking the therapy. Data was broken down by
gender in five of the studies.
Overall, the results showed that use of TZDs
significantly increased the risk of fractures among patients with type 2
diabetes and was associated with changes in bone mineral density at the
lumbar spine and the hip.
Data from the studies that reported sex-specific
results showed that TZDs significantly increased the risk of fractures
among women. They were not, however, associated with the same increase
of fracture risk in men. The studies also showed a consistent decline in
bone mineral density in women exposed to TZD therapy.
There is no clear evidence that other drugs used to
treat type 2 diabetes, such as metformin and sulfonylurea, cause an
increased risk of fractures.
In a related commentary, Dr. Lorraine Lipscombe of
the Institute for Clinical Evaluative Sciences and the University of
Toronto writes that "clinical drug trials are often underpowered to
detect unanticipated and rare adverse effects, and a standardized
postmarketing surveillance process is needed." She cautions that the net
benefit of these drugs is unclear, and there are other effective drugs
that can control glycemia with fewer adverse events.
Curt D. Furberg, M.D., Ph.D., a professor of public
health sciences at Wake Forest University School of Medicine, was also a
researcher on the study.
More News on Diabetes from SeniorJournal.com
Archives
About Rosiglitazone,
marketed as Avandia
Combination products: Avandaryl (containing
rosiglitazone and glimepiride) and Avandamet (containing rosiglitazone
and metformin)
Why is this medication prescribed?
Rosiglitazone is used along with a diet and
exercise program and sometimes with one or more 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). Rosiglitazone 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.
Rosiglitazone 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 occur if high blood sugar is not treated).
How should this medicine be used?
Rosiglitazone comes as a tablet to take by mouth.
It is usually taken once or twice daily with or without meals. Take
rosiglitazone at about the same time(s) every day. Follow the directions
on your prescription label carefully, and ask your doctor or pharmacist
to explain any part you do not understand. Take rosiglitazone exactly as
directed. Do not take more or less of it or take it more often than
prescribed by your doctor.
Your doctor may increase your dose of rosiglitazone
after 8-12 weeks, based on your body's response to the medication.
Rosiglitazone helps control type 2 diabetes but
does not cure it. It may take 2 weeks for your blood sugar to decrease,
and 2-3 months or longer for you to feel the full benefit of
rosiglitazone. Continue to take rosiglitazone even if you feel well. Do
not stop taking rosiglitazone without talking to your doctor.
Other uses for this medicine
This medication may be prescribed for other uses;
ask your doctor or pharmacist for more information.
Warning:
Rosiglitazone and other similar medications
for diabetes may cause or worsen congestive heart failure
(condition in which the heart is unable to pump enough blood to
the other parts of the body). Some studies have shown that
people who take rosiglitazone and insulin are more likely to
have a heart attack or to die of heart problems than people who
take insulin alone. Before you start to take rosiglitazone, tell
your doctor if you have or have ever had congestive heart
failure, especially if your heart failure is so severe that you
must limit your activity and are only comfortable when you are
at rest or you must remain in a chair or bed. Also tell your
doctor if you were born with a heart defect, and if you have or
have ever had swelling of the arms, hands, feet, ankles, or
lower legs; heart disease, high blood pressure; coronary artery
disease (narrowing of the blood vessels that lead to the heart);
a heart attack; an irregular heartbeat; or high cholesterol or
fats in the blood. Your doctor may tell you not to take
rosiglitazone or may monitor you carefully during your
treatment.
If you develop congestive heart failure or
other heart problems, you may experience certain symptoms. Tell
your doctor immediately if you have any of the following
symptoms, especially when you first start taking rosiglitazone
or after your dose is increased: large weight gain in a short
period of time; shortness of breath;swelling of the arms, hands,
feet, ankles, or lower legs; chest pain.swelling or pain in the
stomach; waking up short of breath during the night; needing to
sleep with extra pillows in order to breathe while lying down;
frequent dry cough; or increased tiredness.
Talk to your doctor about the risks of
taking rosiglitazone.
Dec. 10, 2008 The use of thiazolidinediones, a
popular class of oral diabetic drugs, for more than one year by women
with type 2 diabetes significantly reduces bone density, resulting in
the risk of fractures being doubled. The two currently available drugs
in this class are rosiglitazone, marketed as AvandiaTM by
GlaxoSmithKline, and pioglitazone, marketed as ActosTM by Takeda
Pharmaceuticals.