PHILADELPHIA, Dec. 11 /PRNewswire-FirstCall/ -- The following is
GlaxoSmithKline's (NYSE: GSK) response to the retrospective analysis by the
Institute for Clinical Evaluative Sciences (ICES) titled
"Thiazolidinediones and Cardiovascular Outcomes in Older Patients with
Diabetes".
GSK believes that the ICES retrospective analysis of the Ontario Drug
Benefit (ODB) database has significant limitations and generates misleading
conclusions regarding acute myocardial infarction and death. These
conclusions are inconsistent with a more robust body of evidence from
large, long-term, prospective, well-designed clinical studies, including
ADOPT and RECORD.
-- These long-term trials in diabetic patients comparing rosiglitazone to
other oral anti-diabetic medicines show no increased risk for
cardiovascular events compared to other commonly used medications,
other than the well-known risk of congestive heart failure (CHF) with
thiazolidinedione (TZDs).
-- RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of
Glycaemia in Diabetes) was specifically designed to evaluate the
cardiovascular safety of rosiglitazone, and is therefore the most
robust data available. A recently published interim analysis for
myocardial infarction and death from cardiovascular causes, or from any
cause, showed no statistically significant difference between
rosiglitazone in combination with either metformin or sulfonylurea vs.
the active comparators of metformin plus sulfonylurea.
In addition, the RESULT clinical study specifically examined an elderly
diabetic population, ages 59 to 89, in which 43 percent of the patients
were greater than 70 years of age, and demonstrated the safety profile of
rosiglitazone to be consistent with the control medicine (sulfonylurea).
Importantly, the results of this study do not reproduce what is already
known about the risk of CHF in TZD users. TZDs can cause fluid retention
which can lead to or exacerbate heart failure. TZDs also have a similar
increased risk of CHF. Yet, in this analysis, pioglitazone is not
associated with an increased risk of CHF (Adjusted RR of 0.91 (95% CI =
0.52-1.59) whereas rosiglitazone is associated with 2 fold-increased risk
of CHF (Adjusted RR = 1.98 and 95% CI=1.44-2.72) compared to oral
anti-diabetic combination therapy. This is inconsistent with the product
labeling.
Moreover, the authors of this retrospective analysis fail to
acknowledge the findings of large epidemiological studies, encompassing
over 1.3 million patients with type 2 diabetes, as well as other similar
studies presented during the recent FDA Advisory Committee meeting. These
studies have investigated whether use of rosiglitazone in the real world
setting is associated with an increase in myocardial infarction or coronary
revascularization. The majority of these studies show that rosiglitazone is
not associated with an increased risk of myocardial infarction compared to
other anti-diabetic agents.
GSK cites the following as examples of the limitations of this
retrospective analysis:
-- As the authors state, patients on TZDs in their analysis may represent
an older, select group of patients with advanced diabetes and therefore
higher baseline risk for cardiovascular disease.
-- The ODB database is composed of a select group of patients.
Rosiglitazone is only prescribed for those patients who fail
treatment on metformin and sulfonylurea, or for whom sulfonylurea or
metformin are contraindicated. The rosiglitazone patients are
therefore ones with higher baseline risk for cardiovascular disease.
The use of rosiglitazone in this database does not reflect its use
among patients in the real world.
-- Patients prescribed rosiglitazone alone suffered from more chronic
diseases compared with those prescribed pioglitazone alone;
therefore they were sicker patients. However this difference is not
corrected for in the analysis of the data and in the study
conclusions.
-- The TZD monotherapy patient population in the ICES analysis had a
4-fold higher rate of kidney impairment, which is indicative of
patients with more progressive type 2 diabetes.
-- The authors state that the study may have been underpowered to detect
adverse effects associated with pioglitazone because of the relatively
small number of persons prescribed pioglitazone alone. It is stated
that larger studies are needed to better determine the relative
effect of each agent on cardiovascular outcomes.
-- The ICES analysis included insulin therapy within the TZD combination
group but excluded insulin combinations within the comparison group.
Insulin is known to be associated with increased CHF and cardiovascular
risk. Therefore, this biases the TZD combination group towards
increased cardiovascular risk relative to the comparison group. This
also permits more advanced patients, with poor glycemic control and who
are at greater risk of cardiovascular complications, to be included in
the TZD population while excluding them from the control group.
Avandia(R) (rosiglitazone maleate) is a widely studied oral
anti-diabetic medicine for the treatment of type 2 diabetes, and
importantly, Avandia has been shown to control blood sugar for longer than
the most commonly used oral anti-diabetic medicines - up to five years.
When used in the appropriate patient, it is an important treatment option
for health-care professionals managing the chronic and life threatening
disease of diabetes. Across multiple sources of data, there is no
consistent or systematic evidence that rosiglitazone increases the risk of
myocardial ischemic events or death in comparison to other anti-diabetic
agents.
About GlaxoSmithKline
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 in patients with type 2 diabetes.
Avandia can cause or worsen heart failure. If you have severe heart
failure (very poor pumping ability of the heart), you cannot be started on
Avandia. Avandia is also not recommended if you have heart failure with
symptoms (such as shortness of breath or swelling) even if these symptoms
are not severe.
Avandia may increase your risk of other heart problems that occur when
there is reduced blood flow to the heart, such as chest pain (angina) or
heart attack (myocardial infarction). This risk appeared higher in patients
taking medicines called nitrates or insulin. Taking Avandia with insulin or
with nitrates is not recommended.
If you have chest pain or a feeling of chest pressure, you should seek
immediate medical attention, regardless of what diabetes medicines you are
taking.
If you take Avandia, tell your doctor right away if you:
-- Have swollen legs or ankles, a rapid increase in weight or difficulty
breathing, or unusual tiredness
-- Experience changes in vision
-- Become pregnant
Review your medical history and tell your doctor if you:
-- Have heart failure or other heart problems
-- Have liver problems or liver disease
-- Are pregnant or are nursing
Women taking Avandia should know that Avandia may increase the risk of
pregnancy.
More fractures have been observed in women taking Avandia.
For more information about Avandia, please see Patient Information. For
further information on Avandia, please see full Prescribing Information.
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the US Private Securities
Litigation Reform Act of 1995, the company cautions investors that any
forward-looking statements or projections made by the company, including
those made in this Announcement, are subject to risks and uncertainties
that may cause actual results to differ materially from those projected.
Factors that may affect the company's operations are described under 'Risk
Factors' in the 'Business Review' in the company's Annual Report 2006.
SOURCE GlaxoSmithKline
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