Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial

JAMA. 1999 Jan 20;281(3):235-42. doi: 10.1001/jama.281.3.235.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Glucose
  • Blood Pressure
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Double-Blind Method
  • Energy Intake
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin / blood
  • Lactones / therapeutic use*
  • Lipase / antagonists & inhibitors*
  • Lipids / blood
  • Male
  • Obesity / complications
  • Obesity / diet therapy
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Orlistat
  • Risk Factors
  • Weight Loss


  • Blood Glucose
  • Enzyme Inhibitors
  • Insulin
  • Lactones
  • Lipids
  • Orlistat
  • Lipase