EFFICACY AND TOLERABILITY OF ORLISTAT IN THE TREATMENT OF OBESITY - A6-MONTH DOSE-RANGING STUDY

Objective: To determine the weight-reducing efficacy of orlistat, a no vel gastrointestinal lipase inhibitor, and to define the optimal dosag e regimen and establish the tolerability of the drug when used for a 6 -month treatment period.Method's: The study was a multicentre randomis ed, double-blind, parallel group in design and involved 676 obese male and female subjects aged at least 18 years with a body mass index bet ween 28 and 43 kg.m(-2). Following a 5-week placebo run-in period, sub jects were randomised to receive orlistat 30 mg, 60 mg, 120 mg, 240 mg or matching placebo three times a day (tid) for 24 weeks during meals . Patients were maintained on a mildly hypocaloric diet throughout the study period. The primary efficacy parameter was body weight change o ver time. Results: Orlistat resulted in a significantly greater mean l oss of body weight than observed in the placebo group. In absolute ter ms, mean weight loss was greatest in the 120 mg group (9.8%). More orl istat- than placebo-treated patients lost > 10% of initial body weight (37% of the 120 mg group vs 19% of the placebo group). Orlistat was w ell tolerated. Predictably, in view of its known pharmacological effec ts, more orlistat-treated patients experienced gastrointestinal events . Mean levels of vitamins A, D and E, and beta-carotene remained withi n the clinical reference ranges in all treatment groups and rarely req uired supplementation. After 24 weeks, plasma concentrations of orlist at were either non-measurable or detected at the assay's limit of quan titation. Conclusion: Orlistat treatment results in a dose-dependent r eduction in body weight in obese subjects and is well tolerated. Orlis tat 120 mg tid represents the optimal dosage regimen.