Healthcare Industry News:  sanofi-aventis 

Biopharmaceuticals Endocrinology

 News Release - September 15, 2006

Avandia(R) (rosiglitazone maleate) Reduced Risk of Progression From Pre-Diabetes To Type 2 Diabetes by 62 Percent in Largest Completed Diabetes Prevention Trial

41 Million People in the United States Have Pre-diabetes, a Precursor to the Development of Type 2 Diabetes

COPENHAGEN, Denmark and MALMOE, Sweden, Sept. 15 (HSMN NewsFeed) -- In the largest completed diabetes-prevention trial to date, Avandia® (rosiglitazone maleate) reduced the risk of developing type 2 diabetes by 62 percent relative to placebo among individuals at high risk of developing type 2 diabetes. This 62 percent reduction was highly statistically significant (p<0.0001) and additive to standard counseling on healthy eating and exercise, which was provided to all participants in the trial. The results of the landmark study are being reported today both in The Lancet and at the 42nd annual meeting of the European Association for the Study of Diabetes (EASD).

The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial evaluated the likelihood of progression to type 2 diabetes over a three-year median follow-up period among 5,269 participants with a condition known as "pre-diabetes". In pre-diabetes, blood sugar levels are higher than normal but not yet high enough for a diagnosis of type 2 diabetes. Participants included in the study were randomized to rosiglitazone (8 mg daily) or placebo and to ramipril (15 mg daily) or placebo and were assessed every six months for three to five years to determine if rosiglitazone or ramipril can reduce the risk of developing type 2 diabetes in individuals with pre-diabetes, when added to healthy eating and exercise counselling. The DREAM study was not designed as a direct comparison between rosiglitazone and ramipril. Results from the ramipril arm of the study, which increased regression to normoglycemia but did not reduce the risk of diabetes or death, are also being reported at EASD and published separately in New England Journal of Medicine.

In this study, designed and conducted by the Population Health Research Institute at McMaster University, Canada, 10.6 percent of participants receiving rosiglitazone progressed to type 2 diabetes versus 25 percent of participants treated with placebo. In the composite primary endpoint of development of diabetes or death from any cause, rosiglitazone demonstrated a 60 percent risk reduction relative to placebo (p<0.0001).

"The DREAM findings are particularly significant as we are in the midst of an epidemic of type 2 diabetes with global implications. It is also noteworthy that the damaging complications of type 2 diabetes can often precede the diagnosis of this condition by several years," said Dr. Bernard Zinman, DREAM Steering Committee Member, director of the Diabetes Centre, Mount Sinai Hospital and professor of medicine, University of Toronto, Canada. "By demonstrating that rosiglitazone significantly reduced the risk of developing type 2 diabetes, these data provide important evidence that it may be possible to alter the course of rising blood sugar levels and its consequences."

Over the three-year median follow-up period of the trial, 51 percent of the participants receiving rosiglitazone returned to normal blood sugar levels compared to 30 percent of participants receiving placebo. Thus, participants taking rosiglitazone were 70 percent (p< 0.0001) more likely than those taking placebo to return to normal blood sugar levels. As might be expected, participants in the placebo group with higher Body Mass Index (BMI), an indicator of obesity, were more likely than those with lower BMI to progress to type 2 diabetes. However, the risk of developing diabetes did not increase with BMI in the group randomized to rosiglitazone. These findings suggest that rosiglitazone may reduce the risk of developing diabetes that is attributable to obesity.

"GSK is committed to groundbreaking research for the treatment of pre- diabetes and type 2 diabetes in order to improve patient outcomes. We believe the long-awaited findings from the DREAM trial will lead to a better understanding of type 2 diabetes and its treatment," said Dr. Lawson Macartney, senior vice president, Cardiovascular and Metabolic Medicine Development Centre, GlaxoSmtihKline. "The DREAM trial is the largest diabetes prevention trial conducted to date and provides the first body of evidence that rosiglitazone can reduce the risk of progression from pre-diabetes to type 2 diabetes in high-risk patients."

Currently there are no medications indicated for the treatment of pre- diabetes. Rosiglitazone is an approved treatment for type 2 diabetes that improves blood sugar control. It is an insulin sensitizer and works differently than other classes of type 2 diabetes medications by directly targeting a key underlying cause of the disease: insulin resistance.

In the study, rosiglitazone was generally well tolerated. There was no significant difference between the rosiglitazone and placebo groups in withdrawal from study medication before study end, or in the secondary composite endpoint of cardiovascular (CV) events that included myocardial infarction, stroke, CV death, confirmed heart failure, new angina and revascularization procedures (2.9 percent in the rosiglitazone group [75 events]; 2.1 percent in the placebo group [55 events], p=0.15). There was a low number of deaths in the trial and no significant difference between the two groups (1.1 percent in the rosiglitazone group [30 deaths] vs. 1.3 percent in the placebo group [33 deaths], p=0.7). The most commonly reported CV event in the study was revascularization procedures. More events of confirmed heart failure were reported in participants who received rosiglitazone as compared to those who received placebo (0.5 percent in participants randomized to rosiglitazone [14 events] versus 0.1 percent in participants randomized to placebo [2 events], p=0.01). Data presented by McMaster University showed that all cases of heart failure were treated effectively during the trial. Information about the potential for heart failure can be found in rosiglitazone prescribing information. At the conclusion of the study, mean bodyweight in the rosiglitazone group had increased slightly (4.85lb/2.2kg) more than the placebo group.

While not everyone with pre-diabetes develops type 2 diabetes, other large clinical outcomes trials have demonstrated that, without intervention, between 29 to 55 percent of individuals with pre-diabetes develop type 2 diabetes over the course of three years. As type 2 diabetes progresses, the combined effects of insulin resistance and beta-cell dysfunction can make it increasingly difficult for physicians to help patients control blood sugar levels.

About the DREAM Study

DREAM is an international, multi-center, randomized, double-blind, 2x2 factorial trial involving 5,269 participants from 21 countries with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), also known as pre-diabetes, who are therefore a high risk of developing type 2 diabetes. The DREAM study was conducted by Population Health Research Institute at the Michael G. DeGroote School of Medicine at McMaster University and Hamilton Health Sciences in Hamilton Ontario. DREAM was funded by a peer-reviewed grant from the Canadian Institutes of Health Research (CIHR) via the CIHR/Rx&D Collaborative Research Program as well as by GlaxoSmithKline, sanofi-aventis and King Pharmaceuticals.

About Insulin Resistance, Pre-diabetes and Type 2 Diabetes

Insulin resistance occurs when the body does not respond properly to its own natural insulin. Insulin is a hormone in the body that helps convert blood sugar to energy so it can be used by the body's cells. In individuals with insulin resistance, the pancreas tries to keep up with the demand for insulin by producing and releasing more. Eventually, the pancreas cannot keep up with the body's need for insulin, and excess sugar builds up in the bloodstream.

Insulin resistance contributes to the progression from normal blood sugar levels to pre-diabetes to type 2 diabetes. When blood sugar levels are higher than normal, but not yet high enough to be diagnosed as diabetes, the condition is referred to as pre-diabetes. Pre-diabetes is a precursor to type 2 diabetes, however, not everyone with pre-diabetes goes on to develop the disease. Type 2 diabetes occurs either when the body does not produce enough insulin or does not respond properly to its own natural insulin.

In type 2 diabetes, when sugar builds up in the blood instead of going into the cells, it can starve the cells of energy, and over time, high blood sugar levels can cause diabetes-related complications, such as stroke, heart disease, kidney disease, blindness and amputation.

In the United States, 41 million people have pre-diabetes and more than 18 million have type 2 diabetes.

Avandia (rosiglitazone maleate) Indication & Important Safety Information

Avandia, along with diet and exercise, helps improve blood sugar control. It may be taken alone or with other diabetes medicine.

Tell your doctor if you have heart problems or heart failure. Avandia can 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.

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.

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.

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 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 Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2005.

Source: GlaxoSmithKline

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