Close Call for a Diabetes Drug

Diabetes can kill its victims in all manner of nasty ways. The complications include heart disease, stroke and kidney failure--and these are just a few of the ills that can result from the body's inability to process sugar.

It's a cruel twist of fate therefore, that one of the most promising drugs ever found to treat diabetics could turn out to be just another way to die. Yet that's the depressing possibility the Food and Drug Administration was forced to confront last week. At least 35 people have died from liver damage after taking Rezulin, a medication the agency approved two years ago. In an unusual meeting last week, a panel of independent experts wrestled with the question of whether the agency should reverse itself and pull the drug from the market.

In the end the panel said Rezulin should stay in circulation: the dangers are real, but they're outweighed by the drug's lifesaving potential. But even if the FDA goes along with the decision--which it need not but generally does--the very fact that the meeting took place raised questions about the agency's approval process. Rezulin got its thumbs-up via the so-called fast-track system, which slashes through some of the FDA's red tape in order to get an important medication into patients' hands quickly. Drug companies love it, since it gets profits rolling in sooner.

Critics insist that the fast track cuts back on not just bureaucracy but safety too. The FDA has always insisted that any shortcuts it takes are balanced by the tight monitoring of fast-track drugs once they're in use. But in this case, at least, the monitoring was badly inadequate. The panel learned, for example, that 200,000 patients have taken Rezulin for a year or more--or maybe it's 400,000. No one could say if the risk leveled off after six months or kept growing. No one knew if the 35 deaths represented all those who died from Rezulin. Complained panel member Jules Hirsh of Rockefeller University: "The information base is very inadequate."

What the panel didn't question was Rezulin's immense promise. In most folks, insulin (a substance produced in the pancreas) helps ferry blood sugar into cells, where it is used for energy. But for the 15 million or so Americans with Type II diabetes, cells resist insulin's entry; eventually they weaken and die. Traditional treatments involve boosting the amount of insulin available to the cells. But these can have side effects, and for some people they don't work at all.

Rezulin is the first of a new class of drugs that goes directly to the problem and forces cells to accept insulin. And it appears to be effective in hundreds of thousands of patients whose disease isn't controlled by existing treatments. The question, as always, is whether the potential outweighs the risks. The FDA did require Warner-Lambert to keep looking for side effects once Rezulin went on the market, and the company has tightened its instructions to physicians on patient monitoring three separate times since then.

Yet that clearly wasn't enough. Though the panel decided to keep Rezulin on the market, its thumbs-up came with a warning to the FDA to limit the drug's use to patients who are failing other treatments. And the ruling made it clear, implicitly at least, that without adequate follow-up, the agency's streamlined approval process could be a fast track to disaster.