FDA requests withdrawal of sibutramine (Meridia) after the SCOUT trial

The U.S. Food and Drug Administration announced on October 8, 2010 that Abbott Laboratories was pulling the weight-loss drug sibutramine, sold as Meridia, from the U.S. market after a large safety trial pointed to a higher risk of heart attack and stroke ^[2]. The agency formally withdrew approval of the drug's new drug application effective December 21, 2010 ^[1].

The decision rested on the Sibutramine Cardiovascular Outcomes Trial, known as SCOUT. The study showed a 16% increase in the risk of serious cardiovascular events — a composite of nonfatal heart attack, nonfatal stroke, the need for resuscitation after the heart stopped, and cardiovascular death — among patients taking sibutramine compared with those on placebo ^[2].

The regulatory steps were laid out in the Federal Register notice. FDA asked Abbott to voluntarily withdraw Meridia on October 7, 2010, based on its analysis of the SCOUT data ^[1]. Abbott sent a letter dated October 12, 2010 requesting that FDA withdraw approval of NDA 20-632 and waiving its right to a hearing ^[1]. In an acknowledgment letter dated November 1, 2010, FDA said that after reviewing the SCOUT data and the September 15, 2010 meeting of its Endocrinologic and Metabolic Drugs Advisory Committee, the benefits of Meridia for managing obesity "no longer outweigh the risks in any identifiable patient population" ^[1]. The withdrawal notice was signed by Janet Woodcock, then director of the Center for Drug Evaluation and Research, and took effect December 21, 2010 ^[1].

The advisory committee itself had been split. Half the members favored withdrawing sibutramine, while the other half recommended tighter restrictions on access and stronger label warnings ^[2]. FDA ultimately concluded the cardiovascular risks outweighed what it described as the modest weight loss seen with the drug, which the agency had approved in 1997 ^[2].

At an October 8 press conference, John Jenkins, MD, director of FDA's Office of New Drugs, said roughly 100,000 people in the United States were taking sibutramine at the time ^[2]. FDA advised doctors to stop prescribing it and patients to stop taking it and talk with their health care provider about alternatives ^[2]. Jenkins said the agency knew of no withdrawal syndrome tied to the drug and was not aware of long-term consequences for people who stopped, adding that the cardiovascular events in SCOUT probably stemmed from sibutramine raising blood pressure and heart rate — effects that go away once the drug is stopped ^[2].

Why it matters for patients

The Meridia withdrawal reset expectations for what obesity drugs have to prove. After 2010, the question was no longer only how many pounds a medicine takes off, but whether it does so without raising heart risk. That is the reason modern weight-loss and diabetes drugs are studied in long cardiovascular outcomes trials at all.

It also left a thin shelf. At the same press conference, Mary Parks, MD, director of FDA's Division of Metabolic and Endocrine Drug Products, said only a limited number of FDA-approved weight-loss drugs remained: phentermine and diethylpropion for short-term use, and orlistat, available over the counter as Alli and by prescription at a higher dose as Xenical ^[2]. FDA had revised the orlistat label in May 2010 to warn about rare cases of severe liver injury ^[2]. Jenkins said the agency remained "very committed" to working with manufacturers on safe and effective weight drugs, calling obesity "a serious health problem" ^[2].

There is a second, longer-lasting consequence for consumers. On the same day it announced the withdrawal, FDA warned people not to use an internet-sold product called Slimming Beauty Bitter Orange Slimming Capsules because it contained sibutramine that was not listed on the label ^[2]. Once the drug lost its U.S. approval, distributing it in interstate commerce without an approved application became illegal ^[1]. The broader claim that sibutramine went on to become the single most common hidden ingredient in illegal weight-loss supplements is not documented in the sources reviewed here, though the 2010 FDA consumer warning shows the problem existed at the time of withdrawal ^[2].

FDA asked people to report adverse events involving sibutramine or the Slimming Beauty capsules through MedWatch, its safety reporting program ^[2].