FDA Advisory on Sibutramine

This morning, I will be addressing an Advisory Committee appointed by the US Food and Drug Administration (FDA) to evaluate the risk/benefit of sibutramine, an anti-obesity drug that has been on the market for over a decade.

The FDA advisory was prompted by the results of the Sibutramine Cardiovascular OUTcomes (SCOUT) study, published last week in the New England Journal of Medicine.

As blogged previously, the SCOUT study showed a 16% increase in non-fatal heart attacks and stroke on sibutramine compared to placebo.

As also blogged before, the problem with simply extrapolating these findings to patients who would normally be prescribed sibutramine is confounded by the fact that almost all participants in the SCOUT trial had known contraindications to the use of sibutramine and were continued on sibutramine irrespective of whether or not they actually lost weight (something very unlikely to ever happen in clinical practice).

It will be up to the Advisory Committee to decide whether or not the benefit/risk ratio for sibutramine remains favourable in the “on-label” population, i.e. in individuals who do not have a history of cardiovascular disease, have well-controlled blood pressure, and who achieve at least 5% weight loss within the first months of treatment.

This should be an easy decision, as sibutramine is not only an effective anti-obesity drug for a substantial number of patients, but also, despite all the noise to the contrary, has a surprisingly benign side effect profile when used in accordance with the current label.

On the other hand, I would imagine that the Advisors will be most interested in how Abbott (the makers of sibutramine) will help ensure that this drug does not get used by people who really shouldn’t be on it in the first place (i.e. people with pre-existing history of cardiovascular disease, those who do not lose weight and/or experience untoward increases in blood pressure or heart rate).

As I have pointed out before, no effective anti-obesity drug is likely to ever be safe enough to be used by the wrong patients. Indeed, if US doctors cannot be trusted to adequately consider indications and contraindications in their prescriptions of medication, I can think of numerous other drugs that should probably be pulled from the market because they may cause problems when prescribed to the wrong patients without adequate monitoring of side effects.

As heralded by the remarkable media interest in this event, the vote of the Advisory Committee, although not binding for the FDA, will likely have an important signal effect that may well determine the fate of all anti-obesity medications in the foreseeable future.

Anyone interested in the future of pharmacotherapy for obesity should likely be paying close attention to today’s hearing.

Adelphi, MD

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Disclosure: I have received consulting and speaking honoraria from Abbott Laboratories, the makers of sibutramine.

James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL, & SCOUT Investigators (2010). Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. The New England journal of medicine, 363 (10), 905-17 PMID: 20818901