By Daniel DeNoon

Reviewed By Michael Smith, MD
on Wednesday, August 27, 2003

Aug. 27, 2003 -- It lowers blood sugar. It seems to cause weight loss. And now it's the hottest drug in the diabetes pipeline.

It also happens to come from the venom of the Gila monster.

It's called exenatide and it's been grabbing headlines at recent meetings of diabetes specialists. The newest report comes from the 18th International Diabetes Federation Congress in Paris. In a phase 3 clinical trial, exenatide is being used to treat 155 type 2 diabetes patients whose blood sugar remains high despite treatment with standard diabetes drugs.

After 24 weeks' of treatment with exenatide injections, 44% of the patients had their HgA1C levels -- which indicate the average amount of sugar in the blood -- drop to near recommended levels. And they lost weight, too: An average 7.5 pounds, report Kristin Taylor, PhD, and colleagues at Amylin Pharmaceuticals Inc. in San Diego, Calif.

"These results are important, because many patients with type 2 diabetes do not meet treatment targets -- and those that do have difficulty maintaining those targets," says exenatide researcher Michael Nauck, MD, head of the diabetes center at Bad Lauterberg, Germany, in a news release. "The fact that many of the patients who failed to meet targets on other medications were successful in reaching target with exenatide is very encouraging."

A major side effect is nausea, although this seems to get better with continued treatment.

From Lizard Venom to Diabetes Drug

Gila monsters are poisonous lizards. They don't have fangs like vipers. Instead, they grab onto their prey with vice-like jaws while their grooved teeth leak venom-containing spit.

The lizards live in the desert, and eat as few as four times a year. Between meals, their hunger system shuts down. A chemical called exendin-4 is found in their venom. When ingested with saliva, it wakes up the lizards' metabolic system.

Oddly, this reptile molecule works in humans, too. It lowers blood sugar and promotes weight loss. And by a separate mechanism, it protects insulin-producing beta cells in the pancreas and stimulates the growth of new beta cells. Beta cell death is a major factor in progression of type 2 diabetes.

Amylin Pharmaceuticals Inc. and Eli Lilly and Company in Indianapolis, Ind. are developing exenatide. Lilly is a WebMD sponsor.

Alzheimer's Protection, Too?

A compound similar to exenatide has two unpronounceable names: HSEGTFTSD and [Ser(2)]exendin(1-9). In animal studies, this compound protected brain cells from toxic injury by plugging into a brain molecule called GLP-1R.

The report, by University of Auckland researcher Matthew J. During, MD, and colleagues, appears in the August 17 issue of Nature Medicine.

GLP-1R may therefore be a promising target for treatment strategies directed towards degenerative brain and thought disorders, During and colleagues conclude.