First of new class of drugs for diabetes successful

Orlando, FL (June 6, 2004) -- Exenatide, the first of a new class of drugs for type 2 diabetes, was shown to reduce blood glucose (sugar) and body weight, and was associated with improvement in markers of beta cell function, according to a report here today at the American Diabetes Association's 64th Annual Scientific Sessions.

"Because exenatide has multiple underlying anti-diabetes actions -- as well as the ability to promote weight loss, which is often important for people with type 2 diabetes -- it holds the potential to be a pivotally important drug in diabetes care," said Ralph DeFronzo, MD, professor of medicine and chief of the Diabetes Division, University of Texas Health Science Center, San Antonio. "We are pleased that this Phase 3, randomized, placebo-controlled clinical trial -- the gold standard of clinical research -- has produced such positive results for exenatide."

Exenatide was given to 336 people with type 2 diabetes inadequately controlled with maximal doses of metformin, a commonly used drug for the disease. They were randomly assigned to one of three groups to ultimately receive either a five µg or 10 µg dose of exenatide or placebo -- all by subcutaneous injection twice daily. The study continued for 30 weeks.

"Participants who received exenatide had dose-dependant and progressive weight loss with significant reductions in their blood glucose levels by the end of the study," reported Dr. DeFronzo. In the 10 µg group, average weight loss was 6.3 pounds and average reduction in A1C -- a long-term measure of blood glucose control -- was 0.8 percent. The most common side effect of exenatide was mild to moderate nausea.

"Based on the DCCT and UKPDS that assessed the impact of different levels of glucose control on diabetes complications, this magnitude of decline in A1C would be expected to be associated with significant reductions in the development of microvascular complications such as retinopathy, neuropathy and nephropathy," said Dr. De Fronzo.

More than 18 million Americans have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease and amputations. It is the fifth leading cause of death by disease in the U.S.

Exenatide is the first new drug to emerge from exciting research into hormones in the gastrointestinal tract that affect diabetes and weight -- generally known as gut hormones or incretin mimetics. A key hormone produced in the human gut is GLP-1, which can stimulate insulin production without causing the potentially threatening hypoglycemia (low blood sugar levels) associated with insulin injections and some oral anti-diabetes agents (such as sulfonylureas). Mounting evidence suggests that GLP-1 signaling regulates the proliferation of insulin-manufacturing islet cells in the pancreas, thus encouraging the body to make more insulin-producing beta cells.

Exenatide is a synthetic version of exendin-4, a hormone in the saliva of the Gila monster, a lizard native to several Southwestern American states. It displays properties similar to human GLP-1. The lizard eats only four times a year and turns its pancreas off the rest of the time. When it eats, it secretes exendin-4 to turn its pancreas on again.

Research suggests that exenatide exerts its effects through the GLP-1 receptor, is much more potent than GLP-1, and has all of the actions of GLP-1 -- stimulating insulin secretion, slowing gastric emptying and inhibiting production of glucagon by the alpha cells of the pancreas.

"If continued research in humans duplicates all the results we have seen in animal studies -- which have shown that exenatide causes the production of new insulin-producing beta cells -- this would have major implications for the treatment of both type 1 and type 2 diabetes," said Dr. DeFronzo.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit www.diabetes.org. Information from both these sources is available in English and Spanish.