March 7, 2000

Patients, Doctors Not Warned of Dangers of
New Diabetes Drugs

Public Citizen Petitions FDA to Revise Labels for Three Drugs

WASHINGTON, D.C. -- The U.S. Food and Drug Administration (FDA) should immediately revise labels on three new diabetes drugs to warn doctors and patients that the drugs are of questionable effectiveness and can have serious side effects, Public Citizen said in a petition to the FDA.

The drugs, Rezulin, Avandia and Actos, are in a class of drugs called "glitazones." The drugs are used to treat type 2 diabetes, a less severe form of the disease in which patients do not require outside sources of insulin. Glitazones are used to help patients improve their sensitivity to their own insulin. An estimated 15 million people in the U.S. have type 2 diabetes.

Studies have shown that adverse effects of the three drugs can include liver damage, heart damage, weight gain, fluid retention, low blood pressure, anemia and possible changes in hormone levels, Public Citizen s petition says. In addition, studies show that the three drugs are less effective than older drugs. However, this information is either omitted or underplayed in the current label.

These problems were well known to FDA medical officers who reviewed the drugs before they were approved. The medical officers reviews, transcripts from advisory committee meetings, and Public Citizen s own reviews of the medical literature form the basis of the petition.

"It is outrageous that this critical information is being kept from doctors and patients. They need to be aware of the dangers associated with these drugs," said Dr. Sidney M. Wolfe, M.D., director of Public Citizen s Health Research Group. "These drugs have extremely serious adverse effects and are not as effective as some of the older drugs."

One of the drugs, Rezulin, was pulled from the market in 1997 by British medical authorities because of 130 cases worldwide of liver damage, including six deaths. According to a recent statement by the FDA s director of the drug review center, 58 deaths attributed to Rezulin have now been reported to the U.S. agency. Public Citizen petitioned the FDA in 1998 to ban Rezulin. According to a knowledgeable FDA physician, a large proportion of physicians at FDA familiar with Rezulin s dangers think the drug should be taken off the market.

The petition states that:

Results in nine of 10 studies showed that the three drugs were less effective than older drugs. Blood sugar level deteriorated when patients were switched from old drugs to these new drugs;

The FDA has received reports that patients using Rezulin had higher rates of heart failure than patients on older drugs used to treat diabetes. In just the first 18 months that Rezulin was on the market, the FDA listed 56 cases of heart?failure associated with the drug compared to only four cases reported over a period of 13 years for glucotrol (a?sulfonylurea), an older diabetes drug;

The new drugs led to weight gain in various studies of an average of two to 12 pounds;

Some patients using the drugs experienced fluid accumulation in their legs and lungs.

One FDA medical officer wrote, "I am concerned that long-term exposure to [Avandia] may give rise to a similar liver problem as with [Rezulin]" -- that is, the liver failure that drove Rezulin from the market in Great Britain. Two published reports have already documented severe liver damage in patients taking Avandia, but none of the information is in the label, Public Citizen s petition says.

Anemia was another side effect not adequately addressed in the labels, the petition says. The drugs labels mention anemia under "laboratory abnormalities" but dismiss its significance. Although an FDA medical officer wrote of the potential for patients to develop anemia when taking Avandia along with another type 2 diabetes drug with which it is frequently used, the label states that there is no increase in anemia with that drug combination.

Similarly, the labels state that fluid retention occurred in animal and human studies of the drugs, but the labels lack a discussion of the reasons. Without that information, doctors may treat fluid retention with drugs such as calcium channel blockers that could be harmful when taken with the glitazones.

Weight gain was a common problem for all three drugs and appears to be related to how the drugs work in the body. Weight gain puts patients at higher diabetic risks, yet an FDA medical officer wrote that "[Avandia] appears to lower glucose levels by converting glucose to fat."

"Doctors likely will prescribe these drugs inappropriately because they have not been provided any of this critical information," Wolfe said. "That could seriously jeopardize patient health. The FDA should act immediately for the sake of diabetic patients throughout the country."