FDA withdraws Meridia (sibutramine) after SCOUT trial shows 16% rise in heart events

The Food and Drug Administration has withdrawn approval of Meridia (sibutramine), the prescription weight-loss drug made by Abbott Laboratories, after a large cardiovascular outcomes trial showed a 16% increase in serious heart-related events among people taking it compared with placebo ^[1][2]. The withdrawal took effect December 21, 2010 ^[1].

FDA asked Abbott on October 7, 2010, to pull the drug voluntarily, saying its analysis of the Sibutramine Cardiovascular Outcomes Trial (SCOUT) indicated Meridia posed an increased risk of heart attack and stroke ^[1]. The decision was reported on October 8 ^[2]. In a letter dated October 12, 2010, Abbott asked FDA to withdraw approval of the drug and waived its opportunity for a hearing ^[1]. FDA acknowledged the request on November 1, 2010, writing that the benefits of Meridia "no longer outweigh the risks in any identifiable patient population" ^[1]. The notice withdrawing approval was published December 21, 2010, and the withdrawal was effective that day ^[1]. FDA also said distributing the product in interstate commerce without an approved application is illegal and subject to regulatory action ^[1].

What the SCOUT trial found

SCOUT compared sibutramine with placebo and found a 16% increase in the risk for serious cardiovascular events, defined as a combination of nonfatal heart attack, nonfatal stroke, the need for resuscitation after the heart stopped, and cardiovascular death ^[2]. In September 2010, an FDA advisory panel reviewed the results; half of the members favored withdrawing the drug, and the other half recommended stricter access and stronger label warnings ^[1][2]. FDA had approved sibutramine in 1997 ^[2].

At an October 8 press conference, John Jenkins, MD, director of the Office of New Drugs at FDA's Center for Drug Evaluation and Research, said about 100,000 people in the United States were taking sibutramine at the time ^[2]. Asked about what happens when patients stop, Jenkins said he knew of no withdrawal syndrome associated with the drug and was not aware of long-term consequences for patients who stop taking it ^[2]. The cardiovascular events seen in SCOUT, he said, probably came from the drug raising blood pressure and heart rate, effects that disappear once the drug is withdrawn ^[2]. Jenkins also said: "We're still very committed to working with (manufacturers) to help them to develop and gain approval of safe and effective drugs to help patients manage weight. Obesity is a serious health problem." ^[2]

FDA advised doctors to stop prescribing sibutramine and advised patients to stop taking it and talk with their healthcare provider about alternative weight-loss regimens ^[2]. Other FDA-approved weight-loss drugs available at that time included phentermine and diethylpropion for short-term use, and orlistat, sold over the counter as Alli and by prescription as Xenical at a higher dose ^[2]. In May 2010, FDA had revised the orlistat label to warn about rare cases of severe liver injury ^[2].

Separately, FDA warned consumers not to use an Internet-sold weight-loss product called Slimming Beauty Bitter Orange Slimming Capsules because it contained sibutramine that was not listed on the label ^[2].

Why it matters for patients

For the roughly 100,000 Americans taking sibutramine when it was pulled, the decision meant changing treatment rather than weighing a rare side effect: the increase in risk showed up in a trial built to measure cardiovascular outcomes, and FDA concluded the drug's benefits did not outweigh that risk in any patient group it could identify ^[1][2]. FDA said it did not know of a withdrawal syndrome, and that the blood pressure and heart rate effects tied to the drug subside after it is stopped ^[2]. Those were the agency's statements at the time of the withdrawal.

The Slimming Beauty warning points to a second path by which the drug could reach people: a product sold online contained sibutramine without saying so on the label ^[2]. Whether sibutramine remains a common undeclared ingredient in illegal weight-loss supplements has not been reported.

The episode also shows the reach of postmarketing safety studies. It was a trial run after the drug was already on the market, not the original approval studies, that ended sibutramine's US sales ^[1][2]. At the same time, FDA officials used the announcement to say the agency wanted more weight-loss treatments developed and approved, not fewer ^[2]. What drug, if any, would replace sibutramine for a given patient was left to that patient and their clinician to decide ^[2].