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One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor

International Journal of Obesity volume 24, pages 306–313 (2000)Cite this article

Abstract

OBJECTIVE: To assess the efficacy and tolerability of orlistat (Xenical®) in producing and maintaining weight loss over a 12-month period.

DESIGN: Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months.

SETTING: Five centres in the UK.

SUBJECTS: 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74–144 kg).

INTERVENTIONS: All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily.

MAIN OUTCOME MEASURES: Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and β carotene.

RESULTS: Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P<0.05), and 28% and 17%, respectively (P=0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P<0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein:high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and β carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P<0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks.

Conclusions: Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (≥5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.

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References

  1. Higgins M, Kannel W, Garrison R, Pinsky J, Strokes J III . Hazards of obesity. The Framingham experience Acta Med Scand 1988 723 (Suppl): 23–36.

    CAS  Google Scholar 

  2. Pi-Sunyer FX . Medical hazards of obesity Ann Intern Med 1993 119: 655–660.

    Article  CAS  Google Scholar 

  3. Department of Health . The health survey for England. HMSO: London, 1998.

  4. Department of Health . The health of the nation: a strategy for health in England. HMSO: London, 1992.

  5. Bouchard C (ed) . The genetics of obesity. CRC Press: Boca Raton, FL, 1994.

  6. Prentice AM, Jebb SA . Obesity in Britain: gluttony or sloth? Br Med J 1995 7002: 437–439.

    Article  Google Scholar 

  7. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. A report by the Royal College of Physicians . Clinical management of overweight and obese patients with particular reference to the use of drugs. Royal College of Physicians, 1998.

  10. Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, Schaff HV . Valvular heart disease associated with fenfluramine-phentermine New Engl J Med 1997 337: 581–588.

    Article  CAS  Google Scholar 

  11. Cannistra LB, Davis SM, Bauman AG . Valvular heart disease associated with dexfenfluramine New Engl J Med 1997 337: 636.

    Article  CAS  Google Scholar 

  12. Fenfluramine and dexfenfluramine withdrawn. Report from the Medicines Control Agency Curr Probl Pharmacovig 1997 23: 13–14.

  13. Hauptman JB, Jeunet FS, Hartmann D . Initial studies in humans with the novel gastrointestinal lipase inhibitor Ro18-0647 (tetrahydrolipstatin) Am J Clin Nutr 1992 55: 309S–313S.

    Article  CAS  Google Scholar 

  14. 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 Pharmacol Ther 1994 56: 82–85.

    Article  CAS  Google Scholar 

  15. Drent ML, Larsson I, William-Olsson T, Quaade F, Czubayko F, von Bergmann K, Strobel W, Sjöström L, van der Veen EA . Orlistat (RO 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study Int J Obes 1995 19: 221–226.

    CAS  Google Scholar 

  16. Tonstad S, Pometta D, Erkelens DW, Ose L, Moccetti T, Schouten JA, Golay A, Reitsma J, Del Bufalo A, Pasotti E et al.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 

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

    Article  Google Scholar 

  18. Davidson MH, Hauptman J, GiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Chung J, Heymsfield SB . Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat JAMA 1999 281: 235–242.

    Article  CAS  Google Scholar 

  19. Hollander PA, Elbein SC, Hirsch IB, Kelley D, McGill J, Taylor T, Weiss SR, Crockett SE, Kaplan RA, 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  Google Scholar 

  20. Scottish Intercollegiate Guidelines Network . The management of obese patients in Scotland—integrating a new approach in primary health care with a national prevention and management strategy. SIGN, Royal College of Physicians: Edinburgh, 1996.

  21. Schofield WN . Predicting basal metabolic rate, new standards and review of previous work; human nutrition Clin Nutr 1985 39C (Suppl 1): 5–41.

    Google Scholar 

  22. Han TS, van Leer EM, Seidell JC, Lean MEJ . Waist circumference as a screening tool for cardiovascular risk factors: evaluation of Receiver Operating Characteristics (ROC) Obes Res 1996 4: 533–547.

    Article  CAS  Google Scholar 

  23. Lean MEJ, Han TS, Morrison CE . Waist circumference as a measure for indicating need for weight management Br Med J 1995 311: 158–161.

    Article  CAS  Google Scholar 

  24. Guy-Grand B, Apfelbaum M, Crepaldi G, Gries A, Lefebvre P, Turner P . International trial of long-term dexfenfluramine in obesity Lancet 1989 2: 1142–1145.

    Article  CAS  Google Scholar 

  25. Lissner L, Heitmann BL . Dietary fat and obesity: evidence from epidemiology. Eur J Clin Nutr 1995 49: 79–90.

    CAS  PubMed  Google Scholar 

  26. Goldstein DJ . Beneficial health effects of modest weight loss Int J Obes 1992 6: 397–415.

    Google Scholar 

  27. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C . Prospective study of intentional weight loss and mortality in never-smoking US white women aged 40–64 years Am J Epidemiol 1995 141: 1128–1141.

    Article  CAS  Google Scholar 

  28. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C . Prospective study of intentional weight loss and mortality in overweight white men aged 40–64 years Am J Epidemiol 1999 149: 491–503.

    Article  CAS  Google Scholar 

  29. Lean MEJ, Powrie JK, Anderson AS, Garthwaite PH . Obesity, weight loss and prognosis in type 2 diabetes Diabetic Med 1990 7: 228–232.

    Article  CAS  Google Scholar 

  30. Paumgartner G, Sauerbruch . Gallstones: pathogenesis Lancet 1991 338: 1117–1121.

    Article  CAS  Google Scholar 

  31. Melia AT, Koss-Twardy SG, Zhi J . The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers J Clin Pharmac 1996 36: 647–653.

    Article  CAS  Google Scholar 

  32. Zhi J, Melia AT, Koss-Twardy SG, Arora S, Patel IH . The effect of orlistat, an inhibitor of dietary fat absorption, on the pharmacokinetics of β-carotene in healthy volunteers J Clin Pharmac 1996 36: 152–159.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was financially supported by F Hoffmann-La Roche. The authors acknowledge and thank the medical staff, research nurses and dietitians for their work: Dr MK Sridhar, Mrs S Stump, Mrs M Martin, Dr R Stancio and Ms C Hankey.

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Authors and Affiliations

  1. Centre for Obesity Research, Luton and Dunstable Hospital, Lewsey Road, Luton, LU4 0DZ, UK

    N Finer

  2. Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK

    WPT James

  3. St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College Medical School, Turner Street, Whitechapel, London, E1 2AD, UK

    PG Kopelman

  4. Royal Infirmary, Queen Elizabeth Building, Glasgow, G31 2ER, UK

    MEJ Lean

  5. Fazakerley Hospital, Longmoor Lane, Liverpool, L9 7AL, UK

    G Williams

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Finer, N., James, W., Kopelman, P. et al. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes 24, 306–313 (2000). https://doi.org/10.1038/sj.ijo.0801128

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