PHILADELPHIA, Sept. 11 /PRNewswire-FirstCall/ -- GlaxoSmithKline (NYSE:
GSK) believes that conclusions drawn from the most recent meta-analyses
published by Drs. Nissen et. al. and Furberg et. al. in the Journal of the
American Medical Association (JAMA) do not confirm a difference in the
safety profile of Avandia(R) (rosiglitazone) and Actos(R) (pioglitazone).
These analyses reflect limitations that are common to all meta-analyses, by
the authors' own admission. These analyses do not yield data robust enough
to guide doctors in selecting appropriate diabetes treatments for their
patients. Comparisons between different meta-analyses with different
endpoints and patient populations are even more unreliable.
The Actos meta-analysis is based on a small number of studies (19)
provided directly by Takeda, and is heavily biased by data from the
PROactive study (5,238 patients) which contributed 80 percent of the
endpoint data. The patient population in the PROactive study was at high
risk of cardiovascular disease.
-- PROactive compared diabetic patients on Actos to those on placebo.
Patients taking Actos to control blood sugar might be expected to have
fewer cardiovascular events than those who were not controlled on
medication, consistent with the primary results of PROactive (Hazard
Ratio 0.90 p=0.095). However, as described by FDA in the recent
Advisory Committee, at six months PROactive actually showed an
increased risk of heart attack (HR 1.2).
-- Applying the endpoint of CV death, myocardial infarction and stroke to
the data on Avandia across long-term clinical trials to enable a closer
like-for-like comparison with the Actos meta-analysis shows no
statistical difference between Avandia and comparators (a hazard ratio
of 1.03). In RECORD, a study specifically designed to look at
cardiovascular events, no real difference was seen between Avandia and
comparators (HR 0.96). In all of these analyses, the Avandia and the
Actos hazard ratios (HR 0.82 for Actos in Nissen meta-analysis) do not
suggest an increased risk versus the comparators.
-- No long-term, head-to-head clinical trial data specifically evaluates
cardiovascular risk between Avandia and Actos; however, the
head-to-head data that does exist, and the overwhelming majority of
comparative observational data, show no significant differences in CV
events.
The JAMA article on Avandia is yet another iteration of previously
analyzed data, and offers no new information on the safety of Avandia. The
suggested increase in heart attack cited comes from a selective re-analyses
of previously published and highly selective data from only four of 116
available studies, and reflects a difference of only 11 events in 14,291
patients between Avandia and control. In this limited meta-analysis, in the
context of all the other evidence, we believe it is inappropriate for the
author to advise doctors to disregard the FDA's advice which is to keep
patients who are effectively controlling their diabetes on Avandia. These
data have been presented to an expert advisory panel of the FDA, which
voted to keep Avandia available to patients -- a vote that reflects the
role of this medicine as an important treatment option to help diabetes
patients control their blood sugar.
The conclusions of these meta-analyses conflict with the wealth of
accumulated data on Avandia -- including 116 clinical trials in more than
52,000 patients and epidemiological studies of databases in over 1 million
patients. Analyzed studies show no difference in the ischemic
cardiovascular effects of Avandia versus other oral anti-diabetic
medicines, including Actos.
1. Across this extensive data set, the number of heart attacks is small,
and Avandia is shown to have a comparable cardiovascular profile to the
two most prescribed oral anti-diabetic medicines -- metformin and
sulfonylurea -- apart from the well characterized fluid-related events
common to both Avandia and Actos.
2. In three epidemiological studies of databases with more than one
million diabetic patients, the risk of heart attack was similar for
Avandia compared to other anti-diabetic agents. A database study
comparing Avandia to Actos showed no difference between the two.
3. Two large epidemiology studies presented to the FDA Advisory Committee
and conducted independently of GSK by WellPoint and by the Department
of Defense/Tricare also showed no increased rates of heart attack
between Avandia and Actos.
Importantly, only Avandia has been shown to control blood sugar for up
to five years and to be 32 percent more effective than metformin and 63
percent more effective than sulfonylurea in maintaining blood sugar control
over the long-term. We know from clinical studies that effective treatment
of diabetes requires intensive, long-term, day-to-day control of blood
sugar levels to reduce the risk of serious complications (e.g., blindness,
kidney failure, limb amputation, nerve injury) and ultimately save lives.
Avandia is the most widely studied oral medication for Type 2 Diabetes, and
is an important option for physicians who often need to prescribe several
different diabetes medicines in combination to help their patients maintain
blood sugar control.
The FDA is engaged in a full, objective analysis of the science, and
will make its independent recommendations on the appropriate use of oral
anti- diabetic medicines. GSK continues to support Avandia as safe and
effective when used appropriately.
GlaxoSmithKline -- one of the world's leading research-based
pharmaceutical and healthcare companies -- is committed to improving the
quality of human life by enabling people to do more, feel better and live
longer. For company information, visit GlaxoSmithKline on the World Wide
Web at http://www.gsk.com .
Important Safety Information for Avandia(R) (rosiglitazone maleate)
Avandia, along with diet and exercise, helps improve blood sugar control.
It may be taken alone or with other diabetes medicines. Certain people with
heart failure should not take Avandia. Tell your doctor if you have heart
problems or heart failure. Avandia can cause heart failure. Avandia can
also cause your body to keep extra fluid, which leads to swelling and
weight gain. Extra body fluid can make some heart problems worse or lead to
heart failure. If you have swelling or fluid retention, shortness of breath
or trouble breathing, an unusually rapid increase in weight, or unusual
tiredness while taking Avandia, call your doctor right away. For some
people taking Avandia, possible side effects include other heart problems.
Further information regarding potential heart-related risks is currently
under review by the FDA. Talk to your doctor as FDA has made information on
potential heart-related risks available to physicians on its website at
http://www.fda.gov . You should not take Avandia if you have liver
problems. Blood tests should be used to check for liver problems before
starting and while taking Avandia. Tell your doctor if you have liver
disease, or if you experience unexplained tiredness, stomach problems, dark
urine or yellowing of skin while taking Avandia. Tell your doctor about all
of the medicines you are taking. If you are taking Avandia with another
diabetes medicine that lowers blood sugar, you may be at increased risk for
low blood sugar. Ask your doctor whether you need to lower the dose of your
other diabetes medicine. Avandia may increase your risk of pregnancy. Talk
to your doctor before taking Avandia if you could become pregnant or if you
are pregnant. If you are nursing, you should not take Avandia. Talk to your
doctor for advice on how to keep your bones healthy. More fractures,
usually in the upper arm, hand, or foot, have been seen in women taking
Avandia. Your doctor should check your eyes regularly. Very rarely, some
people have experienced vision changes due to swelling in the back of the
eye while taking Avandia.
SOURCE GlaxoSmithKline
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