Drug Derived From Gila Monster Saliva Helps Diabetics Control Glucose, Lose Weight

“The weight loss factor is important because being overweight and weight gain is an almost universal problem for people with diabetes,” said John Buse, M.D., Ph.D., lead researcher in the study and chief of endocrinology in the University of North Carolina at Chapel Hill School of Medicine.

“In that context, it is exciting that patients that continue exenatide injections continue to lose a bit of weight while maintaining blood sugar control, even in their third year of therapy,” Buse said.

“While this weight loss is encouraging, it’s important for people to understand that exenatide is not intended as a weight-loss drug and it is not approved for that purpose,” Buse said. “Only people with type 2 diabetes should take exenatide.”

Exenatide, marketed as Byetta, was approved by the Food and Drug Administration in April 2005 to treat type 2 diabetes in patients who were not able to get their high blood sugar under control in a combination with one or more of three other medications, metformin or sulfonylurea thiazolidinedione.

Weight loss was not the only significant finding. After three years of including exenatide in the drug regimen, 46 percent of participants achieved sustained glucose – or blood-sugar – levels of 7 percent, and 30 percent had levels of 6.5 percent. The ADA considers levels of 7 percent or lower to be healthy.

Exenatide, which is manufactured by Amylin Pharmaceuticals Inc. in collaboration with Eli Lilly and Company, comes in a prefilled pen that type 2 diabetics use to give themselves twice-daily injections within an hour before their morning and evening meals. It is typically given in addition to sulfonylurea, or with a combination of metformin and sulfonylurea.

Exenatide is a synthetic form of a hormone called exendin-4 that occurs naturally in the saliva of the Gila monster, a large venomous lizard native to the southwestern United States and northwestern Mexico. The lizard hormone is about 50 percent identical to a similar hormone in the human digestive tract, called glucagon-like peptide-1 analog, or GLP-1, that increases the production of insulin when blood sugar levels are high. Insulin helps move sugar from the blood into other body tissues where it is used for energy. The lizard hormone remains effective much longer than the human hormone, and thus its synthetic form helps diabetics keep their blood sugar levels from getting too high. Exenatide also slows the emptying of the stomach and causes a decrease in appetite, which is how it leads to weight loss.

The results being reported now come from following patients who took exenatide for three years. In the study, Buse and colleagues analyzed data from 217 diabetes patients. After three years of treatment, most patients showed sustained reductions in blood sugar levels, in blood biomarkers that indicate liver injury and sustained, progressive weight loss averaging 11 pounds.

The study’s co-authors are Leigh MacConell, Ph.D., Anthony H. Stonehouse, Ph.D., Xuesong Guan, James K. Malone, M.D., Ted E. Okerson, M.D., David G. Maggs, M.D. and Dennis D. Kim, M.D. All of the co-authors work for Amylin Pharmaceuticals except for Malone, who works for Eli Lilly and Company. Amylin has a global agreement with Eli Lilly and Company to collaborate on the development and commercialization of exenatide. Funding for this study was provided by Amylin and Eli Lilly and Company.

Buse presented these results June 25, 2007 at the annual scientific sessions of the American Diabetes Association in Chicago.