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.