The prescription diet drug sibutramine, sold under the brand name Meridia, should be taken off the market because it raises the risk of heart attacks and strokes in some patients, the editor of the New England Journal of Medicine said Wednesday.
Those risks, published in January on a government clinical-trials website and now in full in the journal, outweigh the modest benefits of the medication, said Dr. Gregory D. Curfman, the journal’s executive editor and lead author of an editorial that accompanied the study.
The preliminary results published on the government website showed that sibutramine increased the rates of nonfatal heart attacks and strokes in people who had a history of cardiovascular disease and took the medication for an average of 3.4 years. Based on that data, the drug was withdrawn in Europe earlier this year. The U.S. Food and Drug Administration will hold hearings next week to reconsider the drug’s safety.
If the medication is pulled, that would leave Xenical as the only prescription weight-loss medication on the U.S. market other than stimulant medications that are intended only for short-term use.
“Sibutramine doesn’t help people,” Curfman said. “It doesn’t result in very much weight loss, and it doesn’t improve their clinical condition. On the other side, it carries these risks.”
Sibutramine was approved in 1997, but sales of the drug have been modest. The medication works by altering levels of key chemicals in the brain to decrease appetite. It is known to increase blood pressure and heart rate, and the drug is labeled with a warning that it should not be used in patients with heart disease and should not be taken for more than two years.
After the drug’s approval, manufacturer Abbott Laboratories was asked by European regulators to conduct research on the drug in people with a history of cardiovascular disease, diabetes or both. The randomized study of 9,804 overweight or obese people found that the risk of a stroke, heart attack, cardiac arrest or cardiac death was 16% higher among people taking sibutramine compared with those taking a placebo, according to the report published Wednesday.
Overall, nonfatal heart attacks occurred in 4.1% of sibutramine users and 3.2% of the placebo group, and nonfatal strokes occurred in 2.6% of sibutramine users and 1.9% of the placebo group. There was no increased risk of heart attack or stroke in people with diabetes alone.
The participants taking sibutramine lost 9.5 pounds after one year, compared with about 4 pounds in the placebo group. They regained some weight and, by the end of the study, had lost an average of 8.8 pounds since the start of the trial. (The placebo group regained a similar, small amount of weight after the first year.)
The study was conducted to see if weight loss would counteract the bump in blood pressure and heart rate brought on by the drug and, thus, might ultimately be beneficial to people with cardiovascular disease, said the study’s lead author, Dr. Philip James, an obesity researcher at the London School of Hygiene and Tropical Medicine. “But these patients were so vulnerable, it didn’t help,” he said.
The findings do not mean the medication is generally unsafe, James said, pointing out that researchers found no difference in risk among diabetics in the study who took sibutramine compared with diabetics who received the placebo.
“When you give it to people who have not had a heart attack or stroke, we didn’t see the effect,” James said. “The normal prescription requirements, as long as they are followed by doctors and patients, are fine.”
“We believe sibutramine has a positive risk-benefit profile when used in the approved patient population,” said Scott Davies, a spokesman for North Chicago-based Abbott Laboratories. Ninety percent of the patients in the trial would not have been eligible for the drug under the guidelines on the U.S. label, Davies noted.
Still, selecting the right people to receive the drug “gets very tricky in the real world,” Curfman said. “People can have asymptomatic heart disease and not know they have it.”
In exchange for an average weight loss of 8.8 pounds, he said, the patients in the study had a 1 in 70 chance of having a heart attack or stroke.
An FDA advisory committee will meet Sept. 15 to review sibutramine. One day later, the agency will hear input on whether to approve a new weight-loss medication called lorcaserin. The medication, like sibutramine, acts on brain-signaling chemicals to suppress appetite. However, Curfman said, data so far suggest the medication does not increase blood pressure or heart rate.
