Weight management and current options in pharmacotherapy: Orlistat and sibutramine

Background: Chronic obesity is associated with various cardiovascular disorders, including diabetes, dyslipidemia, and hypertension. Pharmacotherapy with antiobesity agents is an important management strategy in conjunction with lifestyle interventions. Objective: This article describes the pharmacologic management of obesity, concentrating on orlistat and sibutramine. Methods: Relevant articles were identified through a MEDLINE search (1966-February 2002) using the terms obesity, overweight, weight loss, antiobesity drugs, orlistat, and sibutramine. The search for efficacy trials was limited to randomized controlled studies of >6 months' duration. Also included in the review were relevant references cited in the bibliographies of identified articles, news reports, and the authors' own data. Results: Orlistat reduces fat absorption by inhibiting gastrointestinal lipases. In randomized, controlled trials of up to 2 years' duration, orlistat plus a hypocaloric diet produced significantly greater weight loss than placebo (P < 0.001). In the maintenance phase, patients taking orlistat had less weight regain than did placebo recipients. The weight reduction with orlistat was also associated with a significant improvement in control of cardiovascular risk factors (P < 0.05). Unlike orlistat, sibutramine works by suppressing appetite; its efficacy, however, was similar to that of orlistat in the identified clinical trials. Orlistat was associated primarily with gastrointestinal side effects. Use of orlistat was associated with minimal drug interactions, except with cyclosporine, with which it should not be taken. Sibutramine was also well tolerated, although it may cause dry mouth, anorexia, and insomnia, and should be used with caution in patients at risk for cardiovascular disease. Conclusions: Orlistat and sibutramine demonstrated a favorable efficacy and safety profile in randomized controlled trials. Current evidence supports their use as adjuncts to lifestyle modifications in the treatment of obesity. Copyright (C) 2003 Excerpta Medica, Inc.