FEATURE: Researchers zero in on new therapies to fight diabetes


Researchers zero in on new therapies to fight diabetes.

Confronted by an epidemic of new diabetes cases, researchers have been beavering away at finding new therapies to control the disease.

According to the American Diabetes Association, there are some 18 million diabetics in the US, and that number is growing at about 7 percent each year. And there are few places where the growth rate is faster than in the South, where a tradition of fatty foods and poor exercise habits has created a prime breeding ground for new cases.

The cost is high. Treating Type 1 and Type 2 diabetes costs about $92 billion per year, which makes diabetes an "as yet unexploited" field for drug companies, notes WR Hambrecht analyst Andrew Forman.

But a number of drug companies have been rushing to fill the gap.

At the recent annual meeting of the ADA, Eli Lilly and Amylin launched Byetta, a new drug for Type 2 sufferers that is the first "incretin mimetic," mimicking the action of the GLP-1 hormone and creating insulin when blood sugar is high.

"It's not insulin, but a copy of a hormone that our gut makes," says Deanna Aftab-Guy, PhD, associate professor of pediatrics in the division of pediatric endocrinology at Vanderbilt University Medical Center. Researchers found that they could take a protein found in the spit of the Gila monster and make it work like GLP-1.

The hormone affects appetite and blood sugar, she explains, instructing the pancreas to put out insulin and slowing the motility of the gut, telling the brain that we're not hungry anymore. Byetta, which is injected twice daily, can be a particular benefit for Type 2 diabetics, who may still produce some insulin naturally and whose oral medications aren't working as desired. In clinical trials, Byetta was given to patients along with sulfonylureas or another common treatment, metformin.

But other drugs are in the pipeline promising new forms of relief.

Merck told the ADA that a Phase II trial of its experimental MK-0431 demonstrated superior glycemic control for patients with type 2 diabetes. Sitagliptin is in a new class of active agents called dipeptidyl peptidase IV (DPP-IV) inhibitors.

Bristol-Myers Squibb and Merck recently wrapped a Phase III study of Pargluva, touting that it helped to significantly reduce blood glucose levels compared to pioglitazone. AstraZeneca has been focusing much of its efforts on developing Galida in the hope that it can treat glucose and lipid abnormalities in type 2 diabetes. And researchers at Metabolex say they're Phase II drug candidate, metaglidasen, has demonstrated positive results in lowering hemoglobin A1c.

"Metaglidasen treats insulin resistance, one of the major underlying causes of type 2 diabetes, and improves glycemic control without increasing body weight or increasing the risk of edema, unlike the currently marketed insulin sensitizers," said Dr. Julio Rosenstock, a practicing endocrinologist at Medical City Dallas and one of the chief investigators.

One of the most exciting developments in Type 1 diabetes research, says Aftab-Guy, focuses on getting the body to produce insulin rather than subject diabetics to an ongoing regimen of painful shots.

Islet cell transplants may prove to be a solution. "The big problem is how do we get all these islet cells," she adds, noting that it could take two or three donors to come up with a sufficient quantity. Investigators believe, though, that new stem cell technology could be an answer, designing cells that could make insulin.

Another experimental process generating buzz in the field centers on technology that would read insulin levels inside a diabetic that could be linked to an insulin pump that would provide insulin as needed. The pump could be located inside the body and refilled every three months while physicians could program it with a remote control device.

Inhaled insulin has largely been restricted to Type 2 sufferers. But as new inhaled insulins are introduced that are more precise, it will become an option for Type 1 cases, says Aftab-Guy. And then there's the MacroPore patch:

"It's a patch that will have insulin implanted on it, which will release insulin" that can be absorbed throughout the day.

"These are all thoughts, options, things being created," notes Aftab-Guy, "but in the future will be there."

John Carroll is editor of FierceBiotech.