Diabetes Drug Rezulin Pulled Off the Market

Graham compared Rezulin's tendency to cause fatal liver failure with the worst side effects associated with the other diabetes drugs. He concluded that Rezulin, by far, is the most dangerous. Graham was one of at least five FDA physicians who challenged top agency officials, beginning at a staff meeting on Jan. 6, by saying that Rezulin's risks outweighed its benefits and that it should be withdrawn.

The removal of Rezulin comes after Warner-Lambert and senior FDA officials had supported its continued use in the face of mounting deaths and recent repudiation of the pill by numerous health insurers and hospitals.

On four occasions after Rezulin was made available for sale in March 1997, the FDA and Warner-Lambert agreed to safety changes in the drug's labeling, instead of pulling the pill off the market.

The FDA's stance stood in stark contrast to that of its counterpart in Britain, the Medicines Control Agency, which oversaw another company's voluntary withdrawal of Rezulin in December 1997. Citing safety concerns, the British authority refused to allow the reintroduction of Rezulin in March 1999.

But within a week, officials at the FDA, on March 26, 1999, convened an advisory committee meeting, dominated by supporters of Rezulin, including paid consultants to Warner-Lambert. At the conclusion of the meeting, Woodcock indicated in an interview that she did not share the concern voiced by Graham, the senior agency epidemiologist, who presented a chilling picture of Rezulin's danger.

Graham told the committee that Rezulin was one of the most dangerous prescription drugs on the market, that every patient taking the pill was at risk of liver failure and that there was no reliable way to safeguard them. This flew in the face of repeated assurances from Warner-Lambert and others at the FDA, who said that patients would be adequately protected by monthly blood tests, intended to monitor their liver functions.

In June 1999, the FDA announced that it would follow the advisory committee's advice and keep Rezulin on the market. In fact, while the FDA said that Rezulin should no longer be used as a stand-alone diabetes treatment, the agency endorsed its expanded use, in "triple combination" with two other diabetes pills.

The FDA's reassessment of Rezulin's safety was in direct response to a December 1998 investigative series by The Times and subsequent articles published by the newspaper focusing on deaths related to the drug and the actions of the agency and Warner-Lambert.