Weight-Loss Drug Safety Questioned

March 19, 2002 -- A national consumer organization wants the Food and Drug Administration to remove the weight-loss drug Meridia from the market because of deaths and health problems it says are associated with the drug.

Meridia has been associated with 29 deaths and 397 serious adverse events such as arrhythmia and high blood pressure in the United States since its approval in 1998, according to the Public Citizen petition to the FDA. The drug is also known as sibutramine.

"The drug should have never been put on the market — the advisory committee and the physician in charge of the drug both recommended against approval," said Dr. Sidney Wolfe, director of Public Citizen in Washington. "This is a mistake that is being corrected. The drug is just not going to survive much longer."

But Abbott Laboratories, which markets the drug under the name Reductil in Italy and Meridia in the United States, stands by the safety of sibutramine. While company officials acknowledged there have been fatalities allegedly related to sibutramine use, they said that obese people have greater health problems generally.

The Public Citizen petition in the United States follows concerns elsewhere over the drug's safety. Early this month, the Italian Health Ministry announced that it was temporarily suspending marketing of all sibutramine-containing products in the wake of two deaths and 50 additional reports of health problems linked to sibutramine use.

Sibutramine was the first weight-loss drug to be given the OK since the 1997 bans on Redux, also known as dexfenfluramine, and fenfluramine, the "fen" in fen-phen, following reports that the drugs caused heart valve damage.

Abbott Stands by Its Product

According to Abbott Laboratories, an estimated 9 million people have taken sibutramine for weight management worldwide since the drug was first approved.

Dr. Eugene Sun, Abbott vice president of pharmaceutical development, said the company is aware of 32 cases of fatalities worldwide with a possible sibutramine link. "We have done a careful analysis of all 32 cases, and in none of those cases do we see a clear link between the use of sibutramine and the deaths," Sun said.

According to Sun's calculations, these numbers add up to a risk of death of 2.1 for every 100,000 obese people taking Meridia. Sun cited data from the Nurses Health Study, a study of more than 100,000 women. The study, founded by the National Institutes of Health, found a death rate of 400 per 100,000 for obese women in general. People who are obese are at increased risk for a host of diseases, including high blood pressure, heart disease and diabetes.

"We're well below the expected death rate in this population," Sun said. "We're talking about a background here of a fairly ill population in which we expect them to have a higher death rate than the normal population."

However, others point out that the actual incidence of adverse reactions to sibutramine are likely to be substantially underreported.

"There is a 10- to 100-fold underreporting of adverse events," Wolfe said. "What gets reported to the FDA is just a tiny fraction of what is going on."

Acceptable vs. Unacceptable Risk

While the same effects on the heart valves that plagued fen-phen and Redux were not noted, sibutramine does have some potentially serious cardiovascular side effects that are noted on the drug's label.

The label warns that Meridia should not be taken by people who have poorly controlled or uncontrolled high blood pressure because of the risk of elevating blood pressure and heart rate.

Some have questioned whether the recent deaths possibly associated with sibutramine could have been due to inappropriate patient selection. Yet others said that Meridia can cause increases in blood pressure even in those that have normal blood pressure, and even small increases can have a big impact.

"It has been estimated that just a [small] change in diastolic blood pressure changes the risk of heart disease by 6 percent and the risk of stroke by 15 percent," said Dr. Donald Hensrud, associate professor of preventive medicine and nutrition at Mayo Medical School and director of the Executive Health Program at the Mayo Clinic in Rochester, Minn.

Hensrud said that in his own experiences treating obese patients with Meridia, he has seen no problems associated with its use and considers it a good fit with overall obesity treatment in a select group of people.

"On average this drug can lead to weight loss of about 10 pounds above placebo," said Hensrud. "In people with obesity, even a modest weight loss of 5 to 10 percent can improve their overall health."

The next step will be for the FDA to consider Public Citizen's petition and possibly convene an advisory committee to consider whether the risks are acceptable, or if Meridia will be the latest diet drug to crumble under safety concerns.