June 7, 2004 (Orlando, Fla.) -- You wouldn't want to meet a Gila monster in a dark alley, or anywhere but the zoo, for that matter, but an experimental drug derived from Gila monster saliva appears to help patients with type 2 diabetes gain control over their blood sugars when other commonly used drugs have failed.
"The reduction in blood sugar and the associated weight loss seen with exenatide is an important combination of effects. With other therapies, improved blood sugar control is often accompanied by weight gain -- and this weight gain can be a significant frustration for people working to achieve better control of their diabetes," says investigator David Kendall, MD, from the International Diabetes Center in Minneapolis, in a news release.
Treats Diabetes Without Weight Gain
Exenatide is a synthetic version of a chemical called GLP-1 that is found in the intestines of humans and in the saliva of Gila monsters. GLP-1 helps the body better use insulin, protects important insulin-releasing cells in the pancreas, and helps the body feel full after a meal.
In an interview with WebMD, Martin Abrahamson, chief medical officer at the Joslin Diabetes Clinic in Boston, says that exenatide and similar drugs in development may have other positive effects on type 2 diabetes.
In type 2 diabetes, the body begins to lose its sensitivity to insulin, an important hormone the body needs to process sugar. The disease also impairs the ability of the pancreas to make insulin. An estimated 90%-95% of the 18 million Americans with diabetes have type 2. Type 2 diabetes, if untreated, can lead to heart and kidney disease, stroke, nerve damage, eye damage, and other serious problems.
Abrahamson tells WebMD that exenatide's positive effects on blood sugar levels, coupled with its apparent ability to preserve beta cells, the insulin-producing cells, are promising.
"What I think may be more interesting with this product, and we need more data to see it, is its impact of this drug on beta-cell number and beta-cell survival," Abrahamson says. "If it's shown to be able to prevent the further loss of beta cells, then the question I would ask is, do you begin to use this earlier on in the onset of diabetes, because we know that when diabetes is diagnosed on average, patients have lost over 50% of beta-cell function."
Good Blood Sugar Control
About 1,000 patients were enrolled in two studies of exenatide, in which patients received either a 10 microgram or 5 microgram dose in an injection twice a day or a harmless placebo injection on the same schedule.
Both studies involved people with type 2 diabetes who were unable to control their blood sugars despite receiving a maximal dose of the drug Glucophage. In the second study, the patients were also taking a different type of diabetes drug, called a sulfonylurea. Both studies ran for 30 weeks.
In the first study, people who received the 10 microgram dose of exenatide achieved a level of blood sugar control that met American Diabetes Association guidelines for adults with diabetes. People receiving the study drug also showed significant reductions in HbA1c (a measure of blood sugars) at week 30 compared with before week 1.
People who received the medication also lost weight during the study -- about 6 pounds in the 10 microgram group and about 3.5 pounds in the 5 microgram group. In contrast, patients on placebo lost less than 1 pound.
In the second study, involving 773 patients who had poor blood sugar control despite taking both Glucophage and a sulfonylurea, about a third of the people who took the 10 microgram dose had normal blood sugar levels at study end.
Side effects from the medication included nausea in about half of the patients. Dangerously low blood sugar levels as a result of the drug, a condition known as hypoglycemia, was infrequent in both studies.
The researchers also showed that after a full year of treatment, the drug continued its effect on weight loss and blood sugar control.
But another study also presented at the meeting suggests that exenatide may get a run for its money.
An experimental drug called LAF237 was also successful in controlling blood sugars compared with placebo in 107 patients in a Swedish study. Unlike exenatide, which needs to be given in injections twice a day, LAF237 is a pill. It works by preventing the action of an enzyme that normally breaks down GLP-1 in the body and causes most of it to be flushed out of the body in urine.
Neither exenatide nor LAF237 has received approval for sale by the FDA.