The Food and Drug Administration (FDA) has identified five new cases of liver failure linked to Rezulin.

According to news wire reports, there have now been 48 cases of patients suffering liver failure after taking the controversial type 2 drug. Twenty-eight of these patients died as a result of the liver failure, and 15 had liver transplants.

Warner-Lambert, which manufactures Rezulin, is puzzled by the new cases of liver failure.

"What is sad in the whole thing is that Rezulin has helped more than 1 million patients," says Anthony Wild, executive vice president of Warner-Lambert. "But, it's not in our interest to do anything that will damage patients, because it will come back to haunt us."

New Labeling Changes

In June, the FDA announced new labeling changes for Rezulin, saying that the drug should be limited to people not adequately controlled by other therapies. The FDA says Rezulin should not be used by itself, but rather, in combination with Glucophage or sulfonylureas. Also, the new labeling requirements specify that patients taking Rezulin should have their liver enzymes tested prior to treatment, and then monthly for the first year of treatment. After the first year, the FDA recommends that Rezulin users be monitored quarterly.

Steven Leichter, MD, FACP, FACE, codirector, West Georgia Center for Metabolic Disorders in Columbus, Georgia, says the new liver monitoring guidelines are only going to make the cost of Rezulin therapy more expensive.

"I don't think, in my 29 years of being a physician involved with diabetes, that I have ever seen a drug as costly as Rezulin," he says. "When you throw in the need for monthly liver function tests and excess physician visits in order to monitor these tests, then the cost will be enormous."

Works Better in Combination Therapy

In June, at the American Diabetes Association's scientific sessions in San Diego, researchers presented the results of a study involving 178 patients who took Rezulin in combination with Glucophage and sulfonylureas. Dr. Jean-Francoise Yale, director of the Metabolic Day Center in Montreal, reported that adding 400 mg. of Rezulin to 1500 mg. per day of Glucophage and the "maximum allowable dose" of a sulfonylurea resulted in a 43 mg/dl reduction in fasting blood sugars, and a 1.3 percentage point reduction in HbA1c.

There was also a 26 mg/dl decline in triglyceride levels when Rezulin was used in combination with Glucophage and a sulfonylurea. Daily insulin dose requirements, however, declined only 2.5 units, which Yale does not consider to be significant.

Forecasters Predict Bleak Future for Rezulin

With the introduction of Avandia and ACTOS, two drugs that act similar in a type 2's body, forecasters are predicting that Rezulin's stronghold on the type 2 market will decrease in the near future. According to financial consultant firm Merrill Lynch, Rezulin, which generated $748 million in sales in 1998, will likely see a 33 percent drop in sales by the end of 1999, and an additional 20 percent drop in 2000.

Warner-Lambert says that it has no plans to withdraw Rezulin from the type 2 drug market.