Diabetes drug is effective in delaying onset of disease

Medication sold as Avandia is tested on 5,000 people over three years

September 16, 2006|By Thomas H. Maugh II | Thomas H. Maugh II,Los Angeles Times

A drug widely used to treat Type 2 diabetes delayed or prevented progression of pre-diabetes to diabetes by more than 60 percent in the largest prevention trial ever conducted, researchers reported yesterday.

More than 41 million Americans have blood glucose abnormalities -- known as pre-diabetes -- that indicate that they might soon develop diabetes, making them good candidates for use of the drug, called rosiglitazone.

There is no treatment but diet and exercise for preventing progression to Type 2 diabetes.

"I think it will change treatment practices if it stands up," said Dr. Andrew Drexler, director of UCLA's Gonda Diabetes Center. He was not involved in the study.

Some physicians, such as Dr. Stuart Weiss of the New York University School of Medicine, have begun giving rosiglitazone to their pre-diabetic patients.

"Getting people on drugs early is a very important thing," he said. The complications of diabetes, such as heart and kidney disease, "occur even before the diabetes is diagnosed. We need to be much more aggressive and get in sooner."

The one important side effect of the drug during the three-year study was an increase in congestive heart failure, although the absolute number of cases was low and physicians were able to manage it successfully.

The results with rosiglitazone, which costs as much as $170 per month, are comparable to those achieved with intensive programs to modify diet and increase exercise.

The results of the study were presented yesterday in Copenhagen to the European Association for the Study of Diabetes. They will be published in today's issue of the journal Lancet.

In the United States, an estimated 18 million people have Type 2 diabetes, and the number has been growing so rapidly that the Centers for Disease Control and Prevention has declared diabetes an epidemic. Worldwide, 220 million people have diabetes; most of them later develop heart disease, kidney disease, blindness or nerve damage, often leading to amputation of limbs.

"Anything we can do to prevent it will have huge public health implications," said Dr. Vivian Fonseca of the Tulane University Health Sciences Center.

Unlike Type 1 diabetes, in which the pancreas stops producing insulin completely, Type 2 diabetes occurs when the pancreas loses part of its ability to produce insulin and the body's cells lose part or all of their ability to use insulin to remove glucose from the bloodstream for use by cells.

Rosiglitazone, sold by Glaxo-SmithKline under the brand name Avandia, increases the sensitivity of cells to insulin.

Earlier studies on treating diabetes had suggested that rosiglitazone and a second drug, ramipril, might also halt progression to diabetes. Ramipril, sold by King Pharmaceuticals Inc. and Wyeth under the brand name Altace, increases production of insulin.

The current study, led by Dr. Hertzel Gerstein of McMaster University in Canada, enrolled 5,269 people with pre-diabetes in 21 countries. All had abnormal readings on either a glucose tolerance test or a fasting glucose test: Their glucose levels in the standard tests were higher than normal but not high enough to be considered full-blown diabetes.

Previous studies have shown that 29 to 59 percent of such pre-diabetic patients will progress to diabetes within three years.

The subjects received daily doses of either rosiglitazone, ramipril, a placebo or both drugs. The two drugs were not compared head-to-head, and the results in patients who received both drugs have not yet been reported. All the subjects received standard counseling about the importance of diet and exercise.

Gerstein reported that 10.6 percent of the 2,365 people who received rosiglitazone progressed to diabetes, compared with 25 percent of the 2,634 given a placebo. Fourteen of those receiving the drug developed congestive heart failure, compared with two of those receiving placebo.

Rosiglitazone is known to cause a buildup of fluids in some patients, which can lead to heart failure. Weiss noted that this can be controlled or prevented by counseling patients to reduce the amount of salt in their diet.

The results suggest, Gerstein said, that for every 1,000 people given rosiglitazone, 144 cases of diabetes will be delayed or prevented, and there will be an extra four cases of heart failure.

While many experts hailed the results, Dr. Al Powers, director of the diabetes research and training center at Vanderbilt University, cautioned against hasty prescribing of the drug.

"People with pre-diabetes don't technically have a disease, and not all develop diabetes," he said. "You are causing a serious disease [in some] with the drug."

He said the cost of rosiglitazone needs to be factored into the risk-benefit equation.

He also pointed out that intensive lifestyle modification, involving dieting and increased exercise, is just as effective, reducing progression to diabetes by 58 percent in a 2002 study: "And it has an outstanding safety profile."

Dr. Anne Peters of USC's Keck School of Medicine agreed that diet and exercise are the best treatment. "The problem is that it is really, really hard to get people to do it. If that doesn't work, the next step is medication."

Thomas H. Maugh II writes for the Los Angeles Times.

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