Objective: To determine the weight-reducing efficacy of orlistat, a novel gastrointestinal lipase inhibitor, and to define the optimal dosage regimen and establish the tolerability of the drug when used for a 6-month treatment period.
Methods: The study was a multicentre randomised, double-blind, parallel group in design and involved 676 obese male and female subjects aged at least 18 years with a body mass index between 28 and 43 kg x m(-2) Following a 5-week placebo run-in period, subjects 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 over time.
Results: Orlistat resulted in a significantly greater mean loss of body weight than observed in the placebo group. In absolute terms, mean weight loss was greatest in the 120 mg group (9.8%). More orlistat- than placebo-treated patients lost > 10% of initial body weight (37% of the 120 mg group vs 19% of the placebo group). Orlistat was well tolerated. Predictably, in view of its known pharmacological effects, more orlistat-treated patients experienced gastrointestinal events. Mean levels of vitamins A, D and E, and beta-carotene remained within the clinical reference ranges in all treatment groups and rarely required supplementation. After 24 weeks, plasma concentrations of orlistat were either non-measurable or detected at the assay's limit of quantitation.
Conclusion: Orlistat treatment results in a dose-dependent reduction in body weight in obese subjects and is well tolerated. Orlistat 120 mg tid represents the optimal dosage regimen.