Abstract

increasing number of Americans, 1 poses a therapeutic challenge to the clinician.Conventional nonpharmacological interventions based on diet and exercise have limited long-term success in producing sustained weight loss. 2,3Obesity induces multiple metabolic abnormalities that contribute to the pathogenesis of diabetes mellitus and cardiovascular disease 4,5 and is associated with increased morbidity and mortality risk. 6,7A need therefore exists for new and effective therapeutic tools.A potentially promising approach is induction of negative energy balance and weight loss by drug-mediated inhibition of nutrient absorption.Orlistat (Xenical, Hoffman La Roche Inc, Nutley, NJ), a minimally absorbable (Ͻ1%) agent that inhibits activity of pancreatic and gastric lipases, blocks gastrointesti-nal uptake of approximately 30% of ingested fat. 8Assuming incomplete energy compensation, the treated subject consuming an average American diet should gradually lose weight and maintain weight loss.The primary aim of this investigation was to test this hypothesis in a large-scale, 2-year, randomized, double-blind, placebocontrolled study.