European Journal of Clinical Pharmacology

, Volume 54, Issue 2, pp 125–132

Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study


  • L. F. Van Gaal
    • Department of Endocrinology, Metabolism and Clinical Nutrition, Faculty of Medicine, University Hospital Antwerp, B-2650 Edegem-Antwerp, Belgium Tel.: +32-3821 3275; Fax: +32 3825 4980
  • J. I. Broom
    • Department of Clinical Biochemistry, Medical School, University of Aberdeen, Aberdeen, AB9 2ZI, United Kingdom
  • G. Enzi
    • Department of Internal Medicine, University of Padova, Via Giustinioni 2, Policlinico, I-35100 Padova, Italy
  • H. Toplak
    • Medizinische Klinik, Karl-Franzens-Universität, Auenbruggerplatz 15, A-8036, Graz, Austria
  • The Orlistat Dose-Ranging Study Group

DOI: 10.1007/s002280050433

Cite this article as:
Van Gaal, L., Broom, J., Enzi, G. et al. E J Clin Pharmacol (1998) 54: 125. doi:10.1007/s002280050433


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 · 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 β-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.

Key words ObesityOrlistat
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© Springer-Verlag Berlin Heidelberg 1998