Magazine article Drug Topics

Diabetes Care: New Research, New Hope

Magazine article Drug Topics

Diabetes Care: New Research, New Hope

Article excerpt

For the 14 million American! who have diabetes, good news is around the corner. The pipeline of diabetes drugs in this country is about to explode. A number of new approaches to treatment are in late phases of clinical development.

Although there is still no cure in sight, new efforts to understand the disease process have resulted in novel compounds to improve glucose control, and promising new agents that may decrease diabetic complications are on the horizon. What follows is a sampling of diabetes drugs that are expected to enter the U.S. market over the next few years.

A new look at Type II

Type II diabetes, a condition in which the body either doesn't secrete enough insulin or doesn't use insulin efficiently, accounts for 95% of cases of diabetes in the United States. Last month, Princeton, N.).-based Bristol-Myers Squibb's Glucophage (metformin) became the first alternative to sulfonylureas to become available for the treatment of Type II diabetes in the United States in almost two decades. Metformin is a biguanide that has a mechanism of action chemically distinct from that of sulfonylureas, which stimulate the pancreas to secrete insulin.

Metformin "does not increase insulin secretion and does not raise insulin levels in patients with Type II diabetes," explained Alan J. Garber, M.D., Ph.D., professor of medicine, biochemistry, and cell biology at Baylor College of Medicine in Houston. "Metformin seems to make insulin more efficient and more effective to prevent the overproduction of glucose by the liver." According to the product labeling, metformin decreases hepatic glucose production, decreases the intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Since it doesn't increase insulin secretion, it is not associated with either hypoglycemia or hyperglycemia, which can occur with sulfonylureas.

Clinical trials have shown that metformin does not cause weight gain and that it modestly improves cholesterol and triglyceride levels. Metformin is indicated as monotherapy or for use in conjunction with sulfonylureas, with which it has a synergistic effect.

Although metformin is a newcomer to the U.S. market, it has been available overseas for about 30 years. Its introduction here was delayed for many years because it is chemically related to phenformin, an agent for Type II diabetes that was removed from the U.S. market in 1977 because it caused fatal lactic acidosis.

Metformin-related lactic acidosis has been reported to appear in three out of 100,000 patients who take the drug for a year and most commonly occurs in patients with renal impairment. The Food & Drug Administration is requiring BMS to conduct a postmarketing surveillance study of 10,000 patients.

Novel approachs

Under study for Type II diabetes are drugs specifically designed to overcome insulin resistance. Troglitazone, an oral agent licensed from Sankyo Co., Tokyo, and being developed by the Warner-Lambert Co., is a thiazolidinedione that is currently in phase 111 clinical trials. Available data indicate that troglitazone improves insulin sensitivity and lowers glucose concentrations. This, in turn, results in a lesser demand for insulin. Speaking at a recent security analysts meeting, Ronnie Cresswell, Ph.D., v.p. and chairman, Parke-Davis Pharmaceutical Research, said, "The benefit to the patient is control of glucose levels without the potential for inducing hypoglycemia."

A study published last year showed that troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with impaired glucose tolerance as well as in patients with normal glucose tolerance. The authors of the study concluded that "the ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM [non-insulin-dependent diabetes mellitus]."

Insulin-like growth factor is another area of exploration. …

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