Peter, Here's what SBH had to say about Avandia
SmithKline Beecham's Rosiglitazone Protects Insulin-Producing Cells In Type 2 Diabetes
Pre-clinical Studies Show Compound Reduces Pancreatic Exhaustion
and Prevents Progression to Diabetes
ADVANCE FOR RELEASE AT 7 P.M. EDT MONDAY, JUNE 15/
ADVANCE/CHICAGO, June 15 /PRNewswire/ -- Two pre-clinical papers presented today at the American Diabetes Association (ADA) 58th Scientific Sessions show that the investigational oral diabetes medication rosiglitazone maleate (Avandia(R), SmithKline Beecham) protects the insulin-producing cells of the pancreas.
In a pre-diabetic animal model, rosiglitazone prevented the pancreatic degeneration that otherwise would have led to diabetes. In a diabetic model, rosiglitazone allowed recovery of the pancreas already strained by producing too much insulin. Pancreatic exhaustion, in which the insulin-producing cells become overworked and decline in function, leads to steadily worsening diabetes. In humans, the corresponding condition often leads to dependence on insulin injections.
Rosiglitazone is an investigational drug in a new class of oral diabetes medicines called thiazolidinediones (TZDs), or insulin sensitivity enhancers. It directly targets insulin resistance -- an underlying condition responsible for type 2 diabetes -- and works by enhancing the body's ability to use its own insulin more effectively.
"Our results show that, in animal models, rosiglitazone can prevent pancreatic exhaustion by enhancing insulin sensitivity," says the lead author of one study, Diane T. Finegood, Ph.D., associate professor, School of Kinesiology at Simon Fraser University, Vancouver, Canada. "If replicated in humans, this may represent a major advance in treatment of the disease. By preventing pancreatic exhaustion, you can prevent progressively worsening diabetes, which often leads people with type 2 diabetes to become dependent on insulin injections."
Pancreatic Size Maintained, Diabetes Prevented
Led by Dr. Finegood, the study group began treating Zucker Diabetic Fatty (ZDF) rats shortly before the onset of diabetes and found that rosiglitazone prevented both diabetes and pancreatic exhaustion in rats when treatment began in the pre-diabetic stage.
Genetically obese ZDF rats are considered a good model for human type 2 diabetes, since their obesity is associated with insulin resistance. As insulin resistance and failure of the pancreatic insulin-producing cells lead to elevated blood sugar levels, diabetes develops. Eventually these animals experience similar long-term diabetic complications to those in humans, such as eye and kidney damage.
Rosiglitazone-treated animals were able to maintain normal blood sugar levels throughout the study. In fact, they were able to maintain blood sugar control with lower circulating insulin levels at the end of the study than at the beginning. This occurred because they were able to use their body's own insulin more efficiently. Moreover, while the mass of insulin-producing cells in untreated controls fell 48 percent during the final two weeks of the study, in rosiglitazone-treated animals the fall was prevented. Thus, rosiglitazone prevented diabetes and preserved not only these animals' ability to make insulin but the insulin-producing cells themselves.
By contrast, in untreated controls, blood sugar levels rose as insulin output fell; by the end of the six-week study, insulin output was less than 20 percent of its starting value and the animals were overtly diabetic.
"These results show that rosiglitazone prevents both diabetes and pancreatic exhaustion when treatment of ZDF rats begins in the pre-diabetic stage," comments Dr. Finegood. "Importantly, our study also demonstrates that rosiglitazone helps preserve the size and function of the pancreas' insulin-producing tissues -- a key factor in preventing pancreatic exhaustion and onset of diabetes."
Pancreatic Recovery
The second group presenting their rosiglitazone data at the ADA meeting studied genetically diabetic (db/db) mice who were already in the early stages of diabetes. The amount of insulin in their pancreas had fallen 70 percent compared to the lean, non-diabetic controls. In six days, mice treated with rosiglitazone normalized blood sugar levels. Within 10 days, the amount of insulin stored in the pancreas and the fraction of the pancreas devoted to insulin synthesis had also returned to normal. Significantly, the researchers found no increase in expression of the insulin gene, ruling out any rosiglitazone effect on insulin synthesis.
"Rosiglitazone normalizes blood sugar without stimulating insulin output, as some older oral diabetes medications do," says study investigator Michael A. Cawthorne, Ph.D., professor, Metabolic Research, University of Buckingham, UK. "Our results document that this normalization of blood sugar not only spares the insulin-producing cells of the pancreas, but if begun early enough, actually allows these cells to recover from the effects of previous insulin overproduction. Assuming these results carry over to humans, they further underscore the importance of early diagnosis and treatment in type 2 diabetes."
"We are very pleased with this preliminary data which suggest that rosiglitazone may preserve pancreatic size and function, and also attack the fundamental problem of insulin resistance in type 2 diabetes," says Jai Patel, M.D., group director, Diabetes and Metabolism, Clinical Research & Development, SmithKline Beecham. "Although it may be years before we have proof that pancreatic recovery is possible in humans, we are excited by the possibilities these two papers raise."
Discovered and developed by SmithKline Beecham, rosiglitazone is currently in phase III clinical trials.
SmithKline Beecham (NYSE: SBH) -- one of the world's leading health care companies -- discovers, develops, manufactures and markets pharmaceuticals, vaccines, over-the-counter medicines and health-related consumer products, and provides health care services including clinical laboratory testing, disease management, and pharmaceutical benefit management.
SOURCE SmithKline Beecham
CO: SmithKline Beecham
ST: Illinois
IN: MTC
SU: PDT
06/12/98 17:14 EDT prnewswire.com
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