Orlistat, a gastrointestinal lipase
inhibitor that reduces dietary fat absorption by approximately 30%,
may promote weight loss and reduce cardiovascular risk factors.
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.
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.
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
Main Outcome Measures
Body weight change and changes in blood
pressure and serum lipid, glucose, and insulin levels.
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.
Two-year treatment with orlistat plus diet
significantly promotes weight loss, lessens weight regain, and improves
some obesity-related disease risk factors.