| OBJECTIVES: This paper describes the methodology of a multicentre
study designed to assess the efficacy and tolerability of orlistat
120 mg tid as therapy for inducing weight loss in excess of that
achieved with a moderately calorie-restricted diet alone. The results
from a single centre are presented to illustrate the nature of the
response. DESIGN: This was a double-blind, randomized, parallel-
group, placebo-controlled multicentre study. A four-week, single-
blind, placebo run-in period preceded a 52 week double-blind
treatment period during which patients received either orlistat or
placebo three times a day. At the start of the run-in period, all
patients were placed on a diet containing approximately 30% of
calories as fat and designed to cause an energy deficit of
approximately 600 kcal/d. SUBJECTS: Patients of either sex, more than
18 y of age, with a body mass index (BMI) between 30 and 43 kg/m2
were eligible for enrolment. MEASUREMENTS: Efficacy assessments
included: measurements of body weight; anthropometry; quality of
life; blood pressure; serum lipids; fasting serum glucose and
insulin. Safety assessments included: adverse events; vital signs;
ECG; renal and gallbladder ultrasound; haematology; serum
biochemistry. OUTCOME: In the single centre there was a reduction in
body weight of 5.5 +/- 4.5 (s.d.) kg (5.7% reduction) in the placebo
group and 8.6 +/- 5.4kg in the orlistat-treated group (8.4%
reduction) by six months. Thereafter, the placebo group tended to
relapse whereas the orlistat group maintained their loss (2.6% vs
8.4% reduction from initial value at 52 weeks). Total and LDL
cholesterol fell by 0.05 mmol/l (1.6%) and 0.14 mmol/l (4.2%),
respectively, in orlistat treated patients. The drop-out rate was 48%
in the placebo group and 39% in the orlistat group. Intestinal
symptoms related to orlistat were significantly increased compared to
placebo but were well tolerated. Fat soluble vitamin levels remained
within the normal range in the treatment group; the reduction seen in
alpha-tocopherol levels in patients receiving orlistat was normalized
by the decrease in plasma cholesterol concentrations. Beta-carotene
and vitamin D concentrations also decreased in orlistat-treated
patients. CONCLUSIONS: This preliminary analysis suggests that
orlistat, when used with a health-promoting low-fat and moderately
energy-restricted diet, confers advantages in the long-term
management of obesity.
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