The Gila monster (Heloderma suspectum) is a poisonous lizard found in rapidly declining numbers in the American Southwest and northern Mexico. Gila Monsters and the Mexican beaded lizard (Heloderma horridum) are the world's only known venomous lizards.

The Gila monster venom contains the drug that we may be able to use some day to regulate blood glucose. It might seem strange that a useful drug could come from Gila monster venom. But, of course, any drug can be a poison if you take too much of it.

Fortunately, we don't need to kill any Gila monsters or squeeze out their venom in order to get this drug. A researcher who was developing a new type of chemical assay synthesized it and a startup biotech company in San Diego is developing it.

In the 1980s an endocrinologist named Dr. John Eng worked in the Solomon A. Berson Research Laboratory, Veterans Affairs Medical Center, Bronx, New York. His mentor there, Dr. Rosalyn S. Yalow, won the 1977 Nobel Prize in Physiology or Medicine for the development of radioimmunoassays of peptide hormones.

Dr. Eng wanted to discover new hormones, he told me recently. Radioimmunoassays are insensitive and not a good way to discover new hormones. But chemical assays are sensitive. So he developed a new type of chemical assay and looked for hormones that no one had discovered.

Dr. Eng first discovered a new hormone in the venom of the Mexican beaded lizard, which in 1990 he named exendin-3. But this hormone was vasoactive, which means that it contracts or dilates blood vessels.

That prompted Dr. Eng to look at the venom of the Gila monster, which is not vasoactive. There he discovered a hormone, which he named exendin-4, that was similar in structure to glucagon-like peptide 1 (GLP-1). While GLP-1 regulates blood glucose and satiety, as a potential drug it has a short half-life requiring multiple daily injections. He published his key paper on exendin-4 in a 1992 issue of The Journal of Biological Chemistry.

But exendin-4 works for 12 or more hours. "That's how it is better," Dr. Eng says. And that is the basis for Amylin Pharmaceuticals in San Diego to invest millions of dollars to develop it.

When Dr. Eng began to realize exendin-4's potential to control diabetes, he told the Department of Veterans Affairs that the agency should patent it. "The VA declined, because at that time inventions must be veteran specific," he recalls. The VA did retain a royalty-free license.

"That put me in a difficult position," he says, "because it meant I had to essentially make a bet. Patenting it came out of my pocket with no guarantee that anything would come of it. I ended up with this patent, and I couldn't develop it. So I went around to drug companies."

Finally, in 1996, Dr. Eng licensed the patent to Amylin, which calls it AC2993. The company completed the Phase 1 study in 1998 and filed an investigational new drug application with the Food and Drug Administration in 1999. Phase 2 studies, announced at the ADA's 2001 Annual Meeting, showed an approximate 1% reduction in A1c after 28 days. Since A1c measures average blood glucose of the past two to three months, this is a lot.

Amylin now has the drug in Phase 3 trials. Eric Shearin, Amylin's manager of investor relations, told me recently that the company expects to report its findings early next year.

The FDA says that there is a 60 percent chance that it will approve a drug in Phase 3 trials. So AC2993 isn't a sure thing.

Currently, the company is studying the use of two injections a day. "The initial target population is for people with type 2 diabetes who have not progressed to taking insulin," Eric says. "It stimulates insulin production when it is needed and is only active when glucose is high." It also reduces appetite, causing some weight loss.

Amylin is also working on alternatives to shots and a long-acting formulation of one shot a month, AC2993 LAR. It is currently in Phase 1.