News Release

New evidence suggests that Avandia improves beta cell function in the pancreas

Peer-Reviewed Publication

Cohn & Wolfe

Improving beta cell function gives hope of slowing progression of type 2 diabetes

SAN ANTONIO, TX (June 10, 2000) - SmithKline Beecham's oral anti-diabetes drug Avandia [rosiglitazone maleate] may improve beta cell function in the pancreas, according to data presented today at the American Diabetes Association (ADA) 60th Scientific Sessions meeting. These data, which are derived from an analysis of the proinsulin to insulin ratio, showed improvements in an indicator of beta cell function after therapy with Avandia. Results from the Homeostasis Model Assessment (HOMA), which were presented at last year's ADA meeting, also support this finding. In type 2 diabetes, beta cell function may fail over time. Improving beta cell function may enhance long-term glycemic control in type 2 diabetes patients, thereby slowing the progression of the disease.

"These data suggest that rosiglitazone [Avandia] improves beta cell function and may therefore maintain beta cell integrity in type 2 diabetes. If supported in long-term studies, this improvement could have profound implications for the slowing of progression of type 2 diabetes," says Alan Garber, M.D., Ph.D., Professor of Medicine, Biochemistry and Cell Biology at Baylor College of Medicine and Chief of Endocrinology, Diabetes and Metabolism at the Methodist Hospital in Houston, Texas, and a leading expert in the field of diabetes treatment.

Slowing Disease Progression
To determine the effect of Avandia on beta cell function, researchers evaluated the change in proinsulin/insulin (PI/IRI) ratio in two studies of patients with type 2 diabetes. In a 26-week study, patients received either Avandia 2 or 4 mg twice daily or placebo. In a 52-week study, patients received either Avandia 2 or 4 mg twice daily or a sulfonylurea (glyburide).

In both studies, the PI/IRI ratio decreased from baseline in patients taking Avandia, indicating an improvement of beta cell function, with a significant decrease from baseline in patients given Avandia 8 mg. In contrast, the PI/IRI ratios increased, in patients given placebo, indicating a negative impact on beta cell function. Similarly, an increase in PI/IRI ratio was seen in the glyburide treatment group, which might not have been predicted using the HOMA analysis.

"While these data are encouraging, long-term studies are underway to confirm that Avandia will indeed slow the progression of the disease. However, glitazones should be considered for early use in this chronic illness while awaiting demonstration of their full potential," says one of the study authors, Martin Freed, M.D., Group Director, Clinical Research and Development, SmithKline Beecham. "SmithKline Beecham has initiated a large, long-term study-A Diabetes Outcome Progression Trial (ADOPT)-to compare the efficacy of Avandia to other commonly used medications and investigate its potential to delay progression of type 2 diabetes."

Measuring Beta Cell Function
It has been observed that the ratio of proinsulin or PI (a hormone produced by the pancreas that is converted into insulin) compared with immunoreactive insulin or IRI is inversely related to beta cell function in type 2 diabetes patients. A reduction in this ratio is considered to indicate an improvement in beta cell function.

"There is currently no uniformally accepted single test for the measurement of beta-cell function in humans and currently several methods are used," says Dr. Garber. "The PI/IRI ratio of measurement is one of several potential indicators of beta cell function."

Avandia for Type 2 Diabetes
Avandia is approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes as both monotherapy and in combination with metformin or a sulfonylurea, and is one of a novel class of oral antidiabetes agents called thiazolidinediones, commonly called glitazones. Since Avandia's approval one year ago (May 25, 1999), more than three million prescriptions have been written, and nearly one million patients have been treated in the United States.

Avandia was generally well tolerated in clinical trials. Commonly reported side effects were upper respiratory tract infections and headaches. As observed with other members of this class of drugs, weight gain has also been reported. Additionally, anemia and edema have been reported in patients taking Avandia. Because thiazolidinediones can cause fluid retention, Avandia should be used with caution in patients with edema or in patients at risk for fluid related adverse events. There was no signal of drug-related jaundice or liver failure in any Avandia clinical studies. Worldwide post marketing experience is consistent with clinical trial findings. Nevertheless, periodic monitoring of liver enzymes is recommended.

Diabetes
Diabetes, which is the sixth highest cause of death by disease in the United States, strikes an estimated 16 million Americans-90 to 95 percent of whom have type 2 diabetes. Type 2 diabetes is one of the most costly health problems in America due to its devastating complications. It is the leading cause of adult blindness, kidney failure and non-traumatic limb loss in the United States. Diabetes is a chronic disease characterized by high blood-sugar levels that result from defects in the body's ability to use and/or produce insulin.

There are two main types of diabetes: type 1 and type 2. People with type 1 diabetes are usually diagnosed when they are children or young adults. In type 1 diabetes, the pancreas makes little or no insulin, so patients must test their blood sugar and inject insulin every day. In type 2 diabetes, the pancreas continues to produce insulin, but the body inefficiently uses the insulin. Many patients with type 2 diabetes will eventually require insulin injections.

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SmithKline Beecham-one of the world's leading healthcare companies-discovers, develops, manufactures and markets pharmaceuticals, vaccines, over-the-counter medicines and health-related consumer products. For company information, visit SmithKline Beecham on the World Wide Web at http://www.sb.com . For Avandia information, visit http://www.avandia.com .

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