Sibutramine in cardiovascular disease: is SCOUT the new STORM on the horizon?

Imagine your favourite pizza, and, after half of it is gone, your desire to eat the rest is gone as well. Sibutramine seems to have just this effect—at least for some. Doesn’t this appear like the ideal scenario for losing weight? We and other authors are not so sure about that. Sibutramine, a centrally acting monoamino (noradrenaline and serotonin) reuptake inhibitor, was originally developed as an antidepressant. Due to its ‘side effect’ of moderate weight loss mainly achieved via increased satiety, the drug was approved and introduced into the US market in 1997, and is today licensed worldwide for the treatment of obesity. The World Health Organization (WHO) estimates that currently there are .1 billion overweight adults worldwide, and that 300 million of them are clinically obese. Indeed, it can be said that obesity has reached epidemic proportions. Some people have approached this problem from a philosophical point of view. The American psychiatrist Thomas Szasz (born 1920) has stated that ‘obesity condenses and expresses a contest between the individual and some other person or persons in his environment over the control of the individual’s body’. However, a wealth of data buttresses the view that obesity is a lot more than that, and that the perturbation is related to the development of diet-related chronic diseases including type 2 diabetes mellitus, cardiovascular diseases, hypertension, and stroke. The sheer volume of data all point in the same direction: it is time to act. More importantly, it is time to fight obesity before chronic diseases develop. Once chronic illnesses become manifest, the situation changes completely, and a higher body mass index (BMI) may have survival benefits, for example in patients with chronic heart failure. A number of randomized, double-blind, placebocontrolled trials have demonstrated the efficacy of sibutramine in losing weight, especially when combined with lifestyle modification and intensive follow-up. Those effects were reproducible in primary care conditions and would therefore be attributable to most individuals with obesity. The results of the Sibutramine Trial of Obesity Reduction and Maintenance (STORM) should also be kept in mind. Of the individuals in this study, 77% lost weight after 6 months of treatment. This effect was sustained in most patients who continued with sibutramine for another 2 years. Nonetheless, sibutramine was associated with several adverse effects, which has given rise to a debate that still endures today. Indeed, the Italian regulatory authority suspended its approval in March 2002 following a publication by British health authorities who suspected an association of sibutramine with two cardiovascular deaths and 212 reports of adverse reactions in sibutramine-treated patients. Moreover, French drug regulators reported 99 instances of sibutramine side effects, 10 of them being serious. Indeed, the drug may account for a small increase in blood pressure and heart rate, which raises suspicion for cardiovascular toxicity. The use of sibutramine is therefore not recommended in patients with uncontrolled hypertension, pre-existing cardiovascular disease, or tachycardia. To date, we do not have any properly designed large-scale clinical trials assessing the effects of sibutramine and its safety profile in patients with established cardiovascular diseases. The Sibutramine Cardiovascular OUTcomes (SCOUT) trial was a double-blind, randomized, placebo-controlled, parallel-group study into the effects of sibutramine 10 mg once daily on mortality in overweight (defined as a BMI 25 and ,27 kg m plus waist circumference 102 cm in men or 88 cm in women) and obese subjects (BMI 27 and 45 kg m) at high risk of a cardiovascular event. All subjects were older than 55 years and had a history of manifest cardiovascular disease or type 2 diabetes mellitus. TorpPedersen et al. report on the effects of sibutramine during the 6-week run-in period of the trial during which all 10 742 patients received treatment with sibutramine. SCOUT has several long-term end-points. However, the present analysis primarily tackles the cardiovascular safety debate. Based on previous reports of increases in blood pressure and heart rate, the investigators predicted a drop-out rate The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.