Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study

Background: Long-term maintenance of weight loss remains a therapeutic chal lenge in obesity treatment. Objective: This multicenter, double-blind, placebo-controlled study was des igned to test the hypothesis that orlistat, a gastrointestinal lipase inhib itor, is significantly more effective than a placebo in preventing weight r egain. Design: Obese subjects who lost greater than or equal to 8% of their initia l body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (418 0-kT/d deficit) with no adjunctive pharmacotherapy were randomly assigned t o receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 tim es daily for 1 y in combination with a maintenance diet to help prevent wei ght regain. Of 1313 recruited subjects [body mass index tin kg/m(2)): 28-43 ], 729 subjects lost greater than or equal to 8% of their initial body weig ht during the 6-mo weight-loss lead-in period and were enrolled in the doub le-blind phase. Results: After 1 y, subjects treated with 120 mg orlistat 3 times daily reg ained less weight than did placebo-treated subjects (32.8 +/- 4.5% compared with 58.7 +/- 5.8% regain of lost weight; P < 0.001). Moreover, more subje cts in the 120-mg orlistat group than in the placebo group regained less th an or equal to 25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentration s than was placebo (P < 0.001). Conclusion: The use of orlistat during periods of attempted weight maintena nce minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.