Withdrawal of sibutramine leaves European doctors with just one obesity drugBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c477 (Published 25 January 2010) Cite this as: BMJ 2010;340:c477
European regulators have suspended the marketing authorisation for the weight loss drug sibutramine, and the US Food and Drug Administration has restricted its licence, amid concerns about a raised risk of heart attacks and strokes.
The European Medicines Agency recommended on Thursday 21 January that doctors stop using the drug because the risks outweigh the benefits. Its recommendation came after the agency’s committee for medicinal products for human use finalised a safety review, prompted by unpublished data from the sibutramine cardiovascular outcomes trial (SCOUT). This six year trial of 10 000 mostly European patients, which began in December 2002, showed a 16% rise in the risk of non-fatal myocardial infarction or stroke in people taking sibutramine, the agency said.
“Doctors should no longer prescribe and pharmacists should no longer dispense the medicine. Patients currently taking sibutramine should make an appointment . . . to discuss alternative measures to lose weight,” it said.
Explaining the decision, it said that the weight loss from sibutramine was “modest.”
The decision to withdraw authorisation from sibutramine may surprise some, because the SCOUT participants had cardiovascular disease or were at high risk of developing it. Sibutramine was already contraindicated in Europe in people with a history of cardiovascular disease or uncontrolled hypertension.
The agency explained: “Because obese and overweight patients are likely to have a higher risk of cardiovascular events, the committee was of the opinion that the data from SCOUT are relevant for the use of the medicine in clinical practice.”
Sibutramine’s manufacturer, Abbott, defended the drug’s risk-benefit profile.
Eugene Sun, vice president of global pharmaceutical research and development at Abbott, said, “We believe there are many patients who benefit from sibutramine and respectfully disagree with the committee’s opinion and the recommendation to suspend the medicine. However, we will act promptly to comply with the committee’s recommendation.”
The FDA, which first highlighted concerns over the SCOUT data, decided to leave the drug on the market but to add contraindications to the US licence.
The FDA said, “The sibutramine drug label already includes warnings against the use of sibutramine in patients with cardiovascular disease. However, based on the serious nature of the review findings, FDA requested and the manufacturer agreed to add a new contraindication.”
The US licence will now list a history of cardiovascular disease as a contraindication, including uncontrolled hypertension.
The FDA provided additional data from the SCOUT study to support its decision. It said that only people with a history of cardiovascular events showed a significant rise in the risk of cardiovascular events while taking sibutramine. In this group 11.9% of people taking placebo and 13.9% of people taking sibutramine had a cardiovascular event (P=0.023). People with diabetes but no history of cardiovascular events showed no difference between the placebo and sibutramine arms in the rate of cardiovascular events.
In the United Kingdom sibutramine was being used to treat about 86 000 patients in the last year for which figures are available, the Medicines and Healthcare Products Regulatory Agency said.
The appetite suppressant rimonabant was taken off the market in October 2008. That leaves European doctors with just one weight loss drug to prescribe to obese patients, the lipase inhibitor orlistat.
Cite this as: BMJ 2010;340:c477