Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study

International Journal of Obesity volume 25, pages 1713–1721 (2001)Cite this article

Abstract

OBJECTIVE: Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients.

DESIGN: A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (−600 kcal/day; ≤30% of calories as fat)), 294 patients were submitted to the hypocaloric diet and randomly assigned to either orlistat 120 mg or placebo three times daily. Patients who completed the double-blind study (n=255) were eligible for participation in a subsequent 24 week open-label orlistat extension phase.

SUBJECTS: Patients with body mass index (BMI) 27–40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1–6.7 mmol/l).

MEASUREMENTS: Efficacy assessments included weight loss, lipid levels, other cardiovascular risk factors and anthropometric parameters. Safety assessments.

RESULTS: Weight loss during run-in was similar in both groups. After randomization, orlistat-treated patients lost significantly more weight than placebo recipients: mean percentage weight loss from start of run-in to week 24 was−6.8% in the orlistat group and −3.8% in the placebo group (P<0.001). Moreover, more patients in the orlistat group than in the placebo group achieved clinically meaningful weight loss of ≥5% (64 vs 39%) or ≥10% (23 vs 13%) at week 24. Treatment with orlistat was associated with significantly greater changes in total cholesterol (−11.9% vs −4.0%; P<0.001) and LDL-C (−17.6 vs −7.6%; P<0.001). For any category of weight loss during the double-blind treatment period, change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients, indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction (P<0.001). Adjunction of orlistat during the extension phase in patients who initially received placebo induced a further decrease in weight, total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo, with the exception of a higher incidence of gastrointestinal events (≥1 event in 64 vs 38% of patients).

CONCLUSION: Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Hecker KD, Kris-Etherton PM, Zhao G, Coval S, Jeor SS . Impact of body weight and weight loss on cardiovascular risk factors Curr Atheroscler Rep 1999 1: 236–242.

    Article  CAS  PubMed  Google Scholar 

  2. NHLBI Obesity Education Initiative Expert Panel . Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the Evidence Report Obes Res 1998 6: (Suppl 2): 51S–209S.

    Google Scholar 

  3. Van Gaal LF, Wauters MA, De Leeuw IH . The beneficial effects of modest weight loss on cardiovascular risk factors Int J Obes Relat Metab Disord 1997 21 (Suppl 1): S5–S9.

    PubMed  Google Scholar 

  4. Hyman FN, Sempos E, Saltsman J, Glinsmann WH . Evidence for success of caloric restriction in weight loss and control. Summary of data from industry Ann Intern Med 1993 119: 681–687.

    Article  CAS  PubMed  Google Scholar 

  5. Goldstein DJ, Parvin JH . Long-term weight loss: the effect of pharmacologic agents Am J Clin Nutr 1994 60: 647–657.

    Article  CAS  PubMed  Google Scholar 

  6. A Report by the Royal College of Physicians Clinical management of overweight and obese patients with particular reference to the use of drugs London: Royal College of Physicians 1998

  7. Kolanowski J . A risk–benefit assessment of anti-obesity drugs Drug Safety 1999 20: 119–131.

    Article  CAS  PubMed  Google Scholar 

  8. Scheen AJ, Lefèbvre PJ . Pharmacological treatment of obesity: present status Int J Obes Relat Metab Disord 1999 23: (Suppl 1): S47–S53.

    Article  Google Scholar 

  9. Guerciolini R . Mode of action of orlistat Int J Obes Relat Metab Disord 1997 21: (Suppl 3): S12–S23.

    Google Scholar 

  10. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB . Weight control and risk factor reduction in obese subjects treated for 2 y with orlistat. A randomized controlled trial JAMA 1999 281: 235–242.

    Article  CAS  PubMed  Google Scholar 

  11. Sjöström L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HPF, Krempf M for the European Multicentre Orlistat Study Group . Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients Lancet 1998 352: 167–172.

    Article  PubMed  Google Scholar 

  12. Rössner S, Sjöstrom L, Noack R, Meinders E, Noseda G on behalf of the European Orlistat Study Group . Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 y treatment with orlistat for obesity Obes Res 2000 8: 49–61.

    Article  PubMed  Google Scholar 

  13. Finer N, James WPT, Kopelman PG, Lean MEJ, Williams G . One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor Int J Obes Relat Metab Disord 2000 24: 306–313.

    Article  CAS  PubMed  Google Scholar 

  14. Hill JO, Hauptman J, Anderson JW, Fujioka K, O'Neil PM, Smith DK, Zavoral JH, Aronne LJ . Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study Am J Clin Nutr 1999 69: 1108–1116.

    Article  CAS  PubMed  Google Scholar 

  15. Zavoral JH . Treatment with orlistat reduces cardiovascular risk in obese patients J Hypertens 1998 16: 2013–2017.

    Article  CAS  PubMed  Google Scholar 

  16. World Health Organization . Energy and protein requirement Report of a joint FAO/WHO/UNU Expert Consultation. Technical Report Series no. 724 WHO: Geneva 1985

    Google Scholar 

  17. Hollander PA, Elbein SC, Hirsch IB, Kelley D, McGill J, Taylor T, Weiss SR, Crockett SE, Kaplan RY, Comstock J, Lucas CP, Lodewick PA, Canovatchel W, Chung J, Hauptman J . Role of orlistat in the treatment of obese patients with type 2 diabetes Diabetes Care 1998 21: 1288–1294.

    Article  CAS  PubMed  Google Scholar 

  18. Hvizdos KM, Markham A . Orlistat. A review of its use in the management of obesity Drugs 1999 58: 743–760.

    Article  CAS  PubMed  Google Scholar 

  19. World Health Organization . Obesity: preventing and managing the global epidemic WHO: Geneva 1998

    Google Scholar 

  20. Astrup A, Rössner S . Lessons from obesity management programmes: greater initial weight loss improves long-term maintenance Obes Rev 2000 1: 17–19.

    Article  CAS  PubMed  Google Scholar 

  21. Datillo AM, Kris-Etherton PM . Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis Am J Clin Nutr 1992 56: 320–328.

    Article  Google Scholar 

  22. Muls E, Kempen K, Vansant G, Cobbaert C, Saris W . The effects of weight loss and apoprotein E polymorphism on serum lipids, apolipoproteins A-I and B, and lipoprotein(a) Int J Obes Relat Metab Disord 1993 17: 711–716.

    CAS  PubMed  Google Scholar 

  23. Leenen R, van der Kooy K, Meyboom S, Seidell JC, Deurenberg P, Westrate JA . Relative effects of weight loss and dietary fat modification on serum lipid levels in the dietary treatment of obesity J Lip Res 1993 34: 2183–2191.

    CAS  Google Scholar 

  24. Hoffman-La . Roche Laboratories, Nutley, New Jersey Data on file

  25. Tonstad S, Pometta D, Erkelens DW, Ose L, Moccetti T, Schouten JA, Golay A, Del Bufalo A, Pasotti E, van der Wal P . The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia Eur J Clin Pharmac 1994 46: 405–410.

    Article  CAS  Google Scholar 

  26. Zhi J, Melia AT, Guerciolini R, Chung J, Kinberg J, Hauptman JB, Patel IH . Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers Clin Pharmac Ther 1994 56: 82–85.

    Article  CAS  Google Scholar 

  27. Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E . Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population New Engl J Med 1995 333: 1308–1312.

    Article  CAS  PubMed  Google Scholar 

  28. Linton MF, Fazio S . Re-emergence of fibrates in the management of dyslipidemia and cardiovascular risk Curr Atheroscler Rep 2000 2: 29–35.

    Article  CAS  PubMed  Google Scholar 

  29. Maron DJ, Fazio S, Linton MF . Current perspectives on statins Circulation 2000 101: 207–213.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was financially supported by NV Roche SA, Belgium. The authors acknowledge and thank the research nurses and dieticians, as well as J Masure, MD, A Lefever, MD, and P Ysebaert (NV Roche SA, Belgium) for logistical support, and Derde MP (DICE) for statistical analysis.

Author information

Author notes

  1. E Muls, J Kolanowski and A Scheen: Obesity Linked with Hypercholesterolemia treated with Xenical.

Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Nutrition, University Hospital, Gasthuisberg, Leuven, Belgium

    E Muls

  2. University Hospital St Luc, Brussels, Belgium

    J Kolanowski

  3. Département de Médecine, Centre Hospitalier Universitaire Sart Tilman, Liége, Belgium

    A Scheen

  4. Department of Endocrinology, Metabolism and Clinical Nutrition, University Hospital Antwerp, Edegem-Antwerp, Belgium

    L Van Gaal

Authors
  1. E Muls
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Kolanowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Scheen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Van Gaal
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

L Van Gaal for the ObelHyx Study Group

Corresponding author

Correspondence to E Muls.

Additional information

The other ObelHyx investigators were: A Bodson, W Coucke, L Crenier, C Daubresse, JC Daubresse, F Duyck, P Ernest, F Féry, J Gérard, T Hartoko, C Herbaut, B Jandrain, G Krzentowski, G Lamberigts, J Leonet, C Litvine, L Messaoudi, G Michel, D Nicolaij, F Nobels, F Peiffer, M Pieron, K Poppe, C Righes, P Taelman, P Van Crombrugge, A Van den Bruel, S Van Imschoot, M Van Ypersele, B Velkeniers, and J Verhelst.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muls, E., Kolanowski, J., Scheen, A. et al. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study. Int J Obes 25, 1713–1721 (2001). https://doi.org/10.1038/sj.ijo.0801814

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801814

Keywords

Search

Advanced search

Quick links