Society and culture

Regulatory approval

Studies are ongoing into reports of sudden death, heart failure, renal failure and gastrointestinal problems. Despite a 2002 petition by Ralph Nader-founded NGO Public Citizen, the FDA made no attempts to withdraw the drug, but was part of a Senate hearing in 2005.[30] Similarly, David Graham, FDA “whistleblower”, testified before a Senate Finance Committee hearing that sibutramine may be more dangerous than the conditions it is used for.

Between January 2003 and November 2005, a large randomized-controlled “Sibutramine Cardiovascular OUTcomes” (SCOUT) study with 10,742 patients examined whether or not sibutramine administered within a weight management program reduces the risk for cardiovascular complications in people at high risk for heart disease and concluded that use of silbutramine had a RR 1.16 for the primary outcome (composit of nonfatal MI, nonfatal CVA, cardiac arrest, and CV death).

In a dissenting article, “Sibutramine: gone, but not forgotten”, David Haslam (chairman of the National Obesity Forum) says that the SCOUT study is flawed as it only covered high-risk patients and did not consider obese patients who do not have cardiovascular complications or similar contraindications.

On January 21, 2010, the European Medicines Agency recommended suspension of marketing authorizations for sibutramine based on the SCOUT study results.

In August 2010 the FDA added a new contraindication for patients over 65 years of age due to the fact that clinical studies of sibutramine did not include sufficient numbers of such patients.

Abbott Laboratories announced on October 8, 2010 that it is withdrawing sibutramine from the US market under pressure from the FDA, citing concerns over minimal efficacy coupled with increased risk of adverse cardiovascular events.

Sibutramine is a monoamine reuptake inhibitor (MRI) that, in humans, reduces the reuptake of norepinephrine (by ~73%), serotonin (by ~54%), and dopamine (by ~16%), thereby increasing the levels of these substances in synaptic clefts and helping enhance satiety; the serotonergic action, in particular, is thought to influence appetite. Older anorectic agents such as amphetamine and fenfluramine force the release of these neurotransmitters rather than affecting their reuptake.

Despite having a mechanism of action similar to tricyclic antidepressants, sibutramine has failed to demonstrate antidepressant properties in animal studies. It was approved by the U.S. Food and Drug Administration (FDA) in November 1997 for the treatment of obesity.

Sibutramine is reported to be a prodrug to two active metabolites, desmethylsibutramine (M1; BTS-54354) and didesmethylsibutramine (M2; BTS-54505), with much greater potency as MRIs.

Unlike other serotonergic appetite suppressants like fenfluramine, sibutramine and its metabolites have only low and likely inconsequential affinity for the 5-HT2B receptor.