A Review of the Metabolic Effects of Sibutramine

T. D. Filippatos; D. N. Kiortsis; E. N. Liberopoulos; D. P. Mikhailidis; M. S. Elisaf

Disclosures

Curr Med Res Opin. 2005;21(3):457-468. 

In This Article

Conclusions and Suggestions for Future Work

Sibutramine exhibits a dual mode of action. It reduces food intake and attenuates the fall in metabolic rate that occurs during weight loss. Sibutramine-induced weight loss and maintenance is associated with an improvement of obesity-related risk factors. Sibutramine reduced the HOMA index and HbA1c levels. Furthermore, sibutramine in most trials had a favourable effect on lipids, especially on HDL cholesterol and TG, as well as on the T CHOL: HDL cholesterol ratio. Sibutramine can reduce serum uric acid concentrations and it exerts a favourable effect on serum adipocytokine levels. Sibutramine also has a positive effect on hyperandrogenaemia in obese women with PCOS. The link between obesity, insulin resistance and hepatic steatosis is increasingly recognised. Therefore, the effect of anti-obesity drugs in NAFLD will need to be assessed. However, it is not possible to distinguish the effects of sibutramine from those of weight loss per se.

The Sibutramine Cardiovascular Outcome (SCOUT) Study has been planned to demonstrate the long-term health benefits of weight management with sibutramine plus lifestyle modifications (diet and exercise).[93,94] This multinational study will recruit more than 10 000 overweight/obese men or women with high cardiovascular risk, ≥55 years old, with a BMI ≥27 kg/m2 or a BMI ≥25 kg/m2 plus an increased waist circumference. High cardiovascular risk will be assessed by the presence of coronary, cerebral and/or peripheral arteriopathy, impaired glucose tolerance or type 2 diabetes plus at least one other established vascular risk factor. Lifestyle interventions and sibutramine or placebo will be given for an average of 4 years. The primary outcome will be cardiovascular morbidity/mortality. This large study will attempt to answer the two fundamental questions of whether long-term weight loss results in health benefits and if adding sibutramine to lifestyle intervention can improve vascular prognosis. Meanwhile, more studies are needed to assess the effect of sibutramine monotherapy or combination therapy with orlistat on emerging vascular risk factors, such as small dense LDL, oxidised LDL, CRP and homocysteine. Studies assessing the prevention of weight gain after smoking cessation are also warranted.

The evidence base to allow direct comparisons between sibutramine, orlistat and both drugs remains limited. A recent paper (2005)[95] and others[48] suggest that the BP lowering effect of orlistat is better but, that sibutramine causes greater weight loss and is generally better tolerated.

In the future it may be possible to predict the response to weight reducing drugs on the basis of genetic testing.[96] Whether such measures will be clinically cost-effective remains to be proven.

The prevalence of metabolic syndrome and diabetes is increasing. Therefore, it is crucial to explore treatments that will prevent their occurrence. In particular, it is of interest that sibutramine improves at least 4 (HDL cholesterol, TG, glucose and waist circumference) out of the 5 criteria required to make a diagnosis of the metabolic syndrome.[97] The effect of sibutramine on the fifth criterion (BP) remains to be established. Since orlistat has been shown to decrease the risk of developing diabetes in obese patients,[65] a similar study should be carried out with sibutramine. Other anti-obesity drugs are currently undergoing phase III trials, such as rimonabant and topiramate.[3] The effect these drugs have on metabolic variables remains to be established when they are used as monotherapy or in combination with sibutramine or orlistat.

Overall, sibutramine is a useful, efficacious and safe drug for the management of obesity.

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