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A Randomized Controlled Trial

Michael H. Davidson, MD; Jonathan Hauptman, MD; Mario DiGirolamo, MD; John P. Foreyt, PhD; Charles H. Halsted, MD; David Heber, MD; Douglas C. Heimburger, MD; Charles P. Lucas, MD; David C. Robbins, MD; Jain Chung, PhD; Steven B. Heymsfield, MD

JAMA. 1999;281:235-242.

Context  Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.

Objective  To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years.

Design  Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.

Setting and Participants  Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m²) evaluated at 18 US research centers.

Intervention  Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n=133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n=138), orlistat, 60 mg (n=152) or 120 mg (n=153) 3 times a day, for an additional 52 weeks.

Main Outcome Measures  Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.

Results  A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean±SEM, 8.76±0.37 kg) than placebo-treated subjects (5.81±0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2±0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26±0.57 kg; 51.3% regain), or placebo (5.63±0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels.

Conclusions  Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.

Author Affiliations: Chicago Center for Clinical Research, Chicago, Ill (Dr Davidson); Department of Medicine, Emory University School of Medicine, Atlanta, Ga (Dr DiGirolamo); Nutrition Research Clinic, Baylor College of Medicine, Houston, Tex (Dr Foreyt); Division of Clinical Nutrition, University of California, Davis (Dr Halsted); Division of Clinical Nutrition, Rehabilitation Center, University of California, Los Angeles (Dr Heber); Department of Nutrition Sciences, University of Alabama (Dr Heimburger), and Preventive and Nutritional Medicine, William Beaumont Hospital, (Dr Lucas) Birmingham, Ala; Penn Medical Laboratories, Medlantic Research Institute, Washington, DC (Dr Robbins); Hoffmann-La Roche Inc, Nutley, NJ (Drs Hauptman and Chung); and St Luke's-Roosevelt Hospital Center, New York, NY (Dr Heymsfield). Dr Lucas is now with Hoffmann-La Roche Inc.

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