A ONE-YEAR TRIAL TO ASSESS THE VALUE OF ORLISTAT IN THE MANAGEMENT OFOBESITY

OBJECTIVES: This paper describes the methodology of a multicentre stud y designed to assess the efficacy and tolerability of orlistat 120 mg tid as therapy for inducing weight loss in excess of that achieved wit h a moderately calorie-restricted diet alone. The results from a singl e centre are presented to illustrate the nature of the response. DESIG N: This was a double-blind, randomized, parallel-group, placebo-contro lled multicentre study. A four-week, single-blind, placebo run-in peri od preceded a 52 week double-blind treatment period during which patie nts received either orlistat or placebo three times a day. At the star t 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 d eficit 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/m(2) were eligible for enrolment. MEASUREMENTS: Efficacy assessment s included: measurements of body weight; anthropometry; quality of lif e; blood pressure; serum lipids; fasting serum glucose and insulin, Sa fety 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 +/- 5.4 kg in the orlistat-treated group (8.4% reduction) by six months. Thereafter, the placebo group tended to relapse whereas the orlistat group mainta ined their weight loss (2.6% vs 8.4% reduction from initial value at 5 2 weeks). Total and LDL cholesterol fell by 0.05 mmol/l (1.6%) and 0.1 4 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. I ntestinal symptoms related to orlistat were significantly increased co mpared 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 no rmalized by the decrease in plasma cholesterol concentrations. Beta-ca rotene and vitamin D concentrations also decreased in orlistat-treated patients. CONCLUSIONS: This preliminary analysis suggests that orlist at, when used with a health-promoting low-fat and moderately energy-re stricted diet, confers advantages in the long-term management of obesi ty.