AN ASSESSMENT OF THE EFFICACY AND SAFETY OF ORLISTAT FOR THE LONG-TERM MANAGEMENT OF OBESITY

Pancreatic and gastric lipases hydrolyze dietary triglycerides into 2- monoacylglycerols and free fatty acids prior to systemic absorption. O rlistat, a potent gastrointestinal lipase inhibitor, is undergoing rev iew by the Food and Drug Administration as a new treatment for obesity . When given with a fat-containing meal, orlistat 120 mg three times a day reduces fat absorption by approximately 30%, which equates to a d ecrease in caloric absorption of approximately 200 kcal/d. A 2 year Eu ropean study found that 75% of obese subjects on low-fat, energy-defic ient diets pills orlistat lost and maintained a modest bur medically s ignificant amount of weight. The loss was twice as high as that of sub jects taking placebo. Side effects in individuals taking the drug, whi ch were related to orlistat's mechanism of action, included oily spott ing, flatulence, and frequent loose stools. Patients did not experienc e frank diarrhea or intestinal malabsorption. Vitamin D and beta-carot ene levels decreased but remained within the normal range. In summary, orlistat is the first example of a new class of antiobesity drugs tha t interferes with dietary fat absorption, enhances weight loss and wei ght maintenance, has tolerable gastrointestinal side effects, and has no major drug toxicity. Orlistat may prove to be useful in clinical pr actice as an adjunct to nonpharmacological weight management intervent ions, particularly low-fat energy-deficient diets. (J. Nutr. Biochem. 9:516-521, 1998) (C) Elsevier Science Inc. 1998.