Even more worrisome, medical experts
point out that the studies analyzed in the NEJM report- – some
lasting as little as 24 weeks – were not designed
to look for heart risks and it may be that higher risks
will appear after a longer term of use. Dr. David Nathan,
Chief of Diabetes Care at Massachusetts General Hospital,
who reviewed the paper for the NEJM, told the Associated
Press, “This analysis is just scratching the
surface of what may be there.”
Major
Failure of Drug Approval Process
Avandia (rosiglitazone) was approved by the FDA in
1999 for the treatment of Type 2 diabetes, a disease
that affects between 18 to 20 million Americans. Following
regulatory approval Avandia was promoted as being safer
than Rezulin, a diabetes drug removed from the market
in 2000 after patients taking the drug developed liver
damage.
Avandia is currently the top-selling
diabetes drug with total US sales of $2.2 billion in
2006, according to IMS Health, a healthcare tracking
information firm. A one-month supply sells for between
$90 and $170, the Associated Press reported on May
23, 2007.
In an editorial accompanying the
NEJM study, Dr. Bruce Psaty of the University of Washington
and Dr. Furberg of Wake Forest University wrote that
the drug “…represents a major failure of
the drug-use and drug-approval processes in the United
States.” They also state, “…the rationale
for prescribing rosiglitazone at this time is unclear,” because
when the drug was approved its benefits were “at
best mixed.”
Warnings
Ignored for Years
Documents dating back 7 years show that the FDA knew
about the risks associated with Avandia yet did little
to protect consumers. The day after the new study appeared
online, on May 23, 2007, Dr. Sidney Wolfe, director
of Public Citizen, a non-profit health research group,
sent a letter to FDA Commissioner Andrew von Eschenbach,
which described a July 16, 2002 FDA memo that showed
FDA scientists had recommended that the label for Avandia
be amended to include post-marketing reports of heart
failure among patients taking the drug.
“The failure of the FDA to
act on the recommendations made almost five years ago
by its Division of Drug Risk Evaluation is yet another
case in which the conclusions of scientists who are
engaged in post-market drug safety review are not taken
seriously enough or addressed soon enough,” Dr.
Wolfe said in a press release.
“As a result,” he stated
further, “millions of people – to the detriment
of their health – are prescribed drugs whose
risks are dangerously understated, instead of being
prescribed safer, equally, or more effective alternative
drugs.”
New
Details Deepen Concerns
Following the NEJM paper a new
study has revealed additional
details on the side effects of Avandia indicating that
the drug causes 50% greater weight gain than similar
medications while doubling the risk of dangerous fluid
retention in the body.
In the new study, a team of researchers
led by Bernd Richter at Heinrich Heine University in
Dusseldorf, Germany, reviewed 18 previous studies involving
8,000 patients. They found the risk of dangerous fluid
retention in the body – edema – doubled
in those taking the Avandia, compared with patients
on other diabetes medications. The diabetics taking
Avandia had a 7% risk of edema – five times higher
than those taking placebos.
Edema is characterized by swelling
of the ankles and legs, but can lead to more than just
discomfort. Richter explains that the extra fluid in
the body can create more work for the heart, causing
a shortness of breath and possibly heart failure.
His team’s analysis also showed
that patients receiving Avandia gained 50% more weight,
on average, than their counterparts on other diabetes
medications (2.1 kilograms compared with 1.4 kg).
These new findings, added to the
earlier results suggesting the increased risk of heart
attack and bone fractures with Avandia, should be a
matter of concern, says Richter, adding that it is
unclear exactly why the drug would cause complications
such as edema: “Nobody knows exactly why this
happens.” Richter believes that the short-term
results he analyzed in his review offer enough reason
to reduce the widespread use of Avandia. “We
don’t have long-term data, and in the meantime
the public takes part in a large-scale experiment.”
References
1. Philip D. Home, D.M., D.Phil.,
Stuart J. Pocock, Ph.D., et.al, for the RECORD Study
Group. Rosiglitazone
Evaluated for Cardiovascular Outcomes — An Interim
Analysis. N EnglJ Med 2007;357 Vol 357:28-38.
2. Richter B, Bandeira-Echtler E,
Bergerhoff K, Clar C, Ebrahim SH. Rosiglitazone
for type 2 diabetes mellitus. Cochrane Database
of Systematic Reviews 2006, Issue 2. Art. No.: CD006063.
DOI: 10.1002/14651858.CD006063. pub2. First published
online: April 19. 2006.
