Diabetes Assn. Softens Its Support of Rezulin

In another blow to the controversial diabetes pill Rezulin, the American Diabetes Assn. on Wednesday distanced itself from the drug.

At the same time, the association reaffirmed its backing of two newer medications, Avandia and Actos, that also lower blood sugar levels for adult-onset diabetics. Clinical trials found these two pills far less toxic to the liver than Rezulin, although all three are of the same chemical class.

The association’s new position contrasts with that of the manufacturer of Rezulin, Warner-Lambert Co., and top officials of the federal Food and Drug Administration, who continue to maintain that Rezulin’s risks are outweighed by its benefits. Instead of ordering withdrawal of Rezulin, the FDA has on four occasions overseen changes in the drug’s safety labeling.

As of last week, the FDA had linked 89 voluntarily reported cases of liver failure, including 61 deaths, to Rezulin. Several of those cases involved patients who had taken Rezulin for 12 to 18 months, according to data obtained from the FDA. The current safety labeling for Rezulin recommends that patients seek liver-function testing monthly during the first year of use and “periodically” thereafter.

The diabetes association, based in Alexandria, Va., has embraced Rezulin over the last three years. For instance, when Rezulin was withdrawn from sale in Britain in December 1997, the association applauded the FDA’s decision to leave it on the U.S. market. But in a prepared statement Wednesday, the association for the first time characterized Rezulin as potentially less safe than Avandia or Actos.

“At this time, the American Diabetes Assn. does not believe--based on publicly available research data--that the safety concerns regarding Rezulin extend to the two other medications which are in the same chemical class of diabetes drugs as Rezulin,” the group said, adding that it “continues to believe that this class of drugs is beneficial.”

Diabetes association president Bruce Zimmerman, an endocrinologist at the Mayo Clinic, said the distancing from Rezulin stemmed from an ongoing assessment of its safety.

“The evolution behind the statement is our own concern about the safety of the medication and the fact that those concerns have continued in spite of the earlier actions of the FDA,” Zimmerman said in an interview. “We don’t want to be in the position of strongly supporting the medication with these major safety issues.”

But at the FDA, two senior officials responsible for keeping Rezulin on the market, Dr. Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, and the center’s deputy director, Dr. Murray M. Lumpkin, have said that the safety of all three drugs must be assessed jointly. The Times reported Friday that Lumpkin, in recent e-mail messages to colleagues, has defended his decision to forestall any action on Rezulin while providing Warner-Lambert with the FDA’s most up-to-date data on all reported adverse reactions to Avandia and Actos.

The FDA, assigned by federal law to ensure that prescription drugs are safe and effective for their intended use, granted “fast-track” approvals to Rezulin in 1997 and to Avandia and Actos in 1999.

Woodcock and Lumpkin were among a handful of senior officials meeting privately Wednesday with FDA Commissioner Jane E. Henney about Rezulin. An FDA spokeswoman, Laura Bradbard, said she could not comment on what was discussed because the meeting was “internal.”

“We are still evaluating the safety profile of Rezulin and . . . Avandia and Actos,” Bradbard said.

A spokeswoman for Warner-Lambert, Carol Goodrich, declined to comment on Wednesday’s developments, saying that the company has been guided only by “a single consideration--the health and safety of people” with adult-onset diabetes. Rezulin has generated sales of $1.8 billion since Warner-Lambert put it on the market in 1997.

Times researcher Janet Lundblad in Los Angeles contributed to this story.

A series of investigative reports on FDA’s “fast-track” approval of Rezulin is on The Times’ Web site: https://www.latimes.com/rezulin