Nearly eight months after Rezulin was pulled off pharmacy shelves in Britain, the FDA was urged to ban the drug by Public Citizen, a consumer advocacy group founded by Ralph Nader.
"How many more Americans will have to die or require liver transplants before [Warner-Lambert] and the FDA take action to protect people in this country by banning the drug?" wrote Public Citizen's Dr. Sidney Wolfe in a July 27 petition filed with the FDA.
The precise number of Rezulin-related deaths and serious injuries remains unclear.
Experts say as few as 1% of harmful side effects from prescription drugs are voluntarily reported by hospitals, doctors and pharmacists to the FDA or manufacturers. In addition, it is often difficult to establish proof that the use of any drug caused a death by itself. Because of this, FDA officials said, their practice is to say that a drug is "associated" with a death.
Because of the voluntary reporting system, officials acknowledged that they do not know the true number of casualties among Rezulin users.
"I think we really can't say," said the FDA's Bilstad.
For Americans with adult-onset diabetes, Warner-Lambert originally heralded Rezulin, a tan-tinted oval pill, as a breakthrough: potent enough to lower blood-sugar levels and virtually free of harmful side effects.
Progress in the treatment of diabetes is important because the disease is the seventh-leading cause of death in the United States; each year it claims the lives of close to 200,000 Americans.
For the estimated 800,000 people afflicted with Type 1, or juvenile-onset, diabetes, the pancreas fails to produce insulin, the hormone that influences how cells use sugar from blood. Without daily insulin, these patients will die.
With Type 2, or adult-onset, diabetes, blood-sugar levels are higher than normal, but the body still produces insulin. About half of the nation's cases of Type 2 diabetes show no symptoms or are not diagnosed, experts say.
Although Type 1 diabetes poses a more imminent threat of death if left untreated, Type 2 diabetes is where most of the treatment money is to be made because of the higher number of patients.
Since its introduction, Rezulin has climbed quickly toward the "billion-dollar blockbuster" status envisioned by Warner-Lambert. Rezulin has won a following among patients who say they prefer the convenience of a once-a-day pill to some competing medications.
Rezulin is one of 10 competing medications that can lower patients' blood sugar. And, for the limited number of adult-onset diabetics who take insulin, Rezulin has allowed some to halt their injections and many others to reduce their dosages.
Patricia J. Holland, a technical writer at Cornell University, was found to have Type 2 diabetes two years ago. The first year, she said, was "a nightmare" as she tried one oral drug after another that caused her considerable pain, including severe gastric distress. She said this changed when she switched to Rezulin more than a year ago.
"It's been great," Holland said. "It's the only medication for diabetes I take, and it has no side effects. My blood sugar is near normal all the time, and I can eat pretty normally, within reason."
Several diabetes specialists said they prescribe Rezulin in limited circumstances. They cited the risk of sudden liver failure and the expense: About $5 per pill, more than twice as much as the other drugs available for Type 2 diabetics.
"There are other viable treatment options for most Type 2 diabetic patients," said Dr. Bruce Zimmerman, an endocrinologist at the Mayo Clinic and president-elect of the American Diabetes Assn.
Zimmerman noted that doctors at the Mayo Clinic suspect that liver complications caused by Rezulin led to the death of a man treated there last spring.
"I've probably discontinued [Rezulin] more than I've started patients on it," he said.
FDA Role Illustrated by Thalidomide Case
A central responsibility of the FDA is to ensure that prescription drugs are both safe and effective.
The gravity of this role was starkly illustrated in the early 1960s when an agency doctor, Frances O. Kelsey, detected worrisome problems with a sedative called thalidomide. On the strength of her recommendation, FDA officials kept it off the U.S. market.
Kelsey was recognized as a hero after the drug's use by expectant European and Canadian mothers was linked to severe birth defects in at least 10,000 babies. She was saluted by members of Congress and President Kennedy, who presented her the Award of Distinguished Federal Service.
Yet for years, critics also have contended that the FDA took too long to evaluate proposed drugs. These complaints crested with the AIDS epidemic, when activists persuaded the FDA to allow experimental use of certain non-approved drugs.
But the push for faster approval of more drugs did not stop with AIDS. On Nov. 15, 1994, incoming House Speaker Newt Gingrich (R-Ga.) weighed in, calling the then-commissioner of the FDA, Dr. David A. Kessler, "a bully and a thug."