Drugs

, Volume 65, Issue 10, pp 1391–1418 | Cite as

Pharmacotherapy for Obesity

  • Lisa L. Ioannides-Demos
  • Joseph Proietto
  • John J. McNeil
Review Article

Abstract

Pharmacotherapy for the management of obesity is primarily aimed at weight loss, weight loss maintenance and risk reduction, and has included thyroid hormone, amphetamines, phentermine, amfepramone (diethylpropion), phenylpropanolamine, mazindol, fenfluramines and, more recently, sibutramine and orlistat. These agents decrease appetite, reduce absorption of fat or increase energy expenditure.

Primary endpoints used to evaluate anti-obesity drugs most frequently include mean weight loss, percentage weight loss and proportion of patients losing ≥5% and ≥10% of initial body weight. Secondary endpoints may include reduction in body fat, risk factors for cardiovascular disease and the incidences of diseases such as diabetes mellitus.

Most pharmacotherapies have demonstrated significantly greater weight loss in patients on active treatment than those receiving placebo in short-term (≤1 year) randomised controlled trials of pharmacological treatment in conjunction with a calorie-controlled diet or lifestyle intervention. The evidence of long-term efficacy is limited to sibutramine (2 years) and orlistat (4 years). These are the only drugs currently approved for the long-term management of obesity in adults. Sibutramine recipients randomised following 6 months’ treatment to either sibutramine or placebo demonstrated significantly better weight maintenance at 2 years than those taking placebo (p < 0.001), with ≥10% loss of initial bodyweight in 46% of patients. For patients taking orlistat, weight loss was 2.2kg greater than those on placebo at 4 years (p < 0.001), with significantly more patients achieving ≥10% loss of initial bodyweight (26.2% and 15.6%, respectively; p < 0.001).

Other drugs that have been evaluated for weight loss include ephedrine, the antidepressants fluoxetine and bupropion, and the antiepileptics topiramate and zonisamide. Two clinical trials with fluoxetine both reported no significant difference in weight loss compared with placebo at 52 weeks. Clinical trials evaluating ephedrine, bupropion, topiramate and zonisamide have demonstrated significantly greater weight loss than placebo but have been limited to 16–26 weeks’ treatment.

A major obstacle to the evaluation of the clinical trials is the potential bias resulting from low study completion rates. Completion rates varied from 52.8% of phentermine recipients in a 9-month study, to 40% of fenfluramine recipients in a 24-week comparative study with phentermine and 18% of amfepramone recipients in a 24-week study. One-year completion rates range from 51% to 73% for sibutramine and from 66% to 85% for orlistat. Other potential sources of bias include run-in periods and subsequent patient selection based on compliance or initial weight loss.

Several potential new therapies targeting weight loss and obesity through the CNS pathways or peripheral adiposity signals are in early phase clinical trials. Over the next decade the drug treatment of obesity is likely to change significantly because of the availability of new pharmacotherapies to regulate eating behaviours, nutrient partitioning and/or energy expenditure.

Keywords

Topiramate Ephedrine Orlistat Rimonabant Sibutramine 

Notes

Acknowledgements

We would like to thank Professor Paul O’Brien, Director, Centre for Obesity Research and Education, Monash University, for reviewing the manuscript and providing us with some constructive criticism.

Professor Proietto is the chair of the Medical Advisory Board for Optifast® for Novartis and a member of the Australian Advisory Boards for Reductil® (Abbott) and Xenical® (Roche), and Professor John McNeil was a member of the Reductil® (Abbott) Advisory Board.

References

  1. 1.
    Farrigan C, Pang K. Obesity market overview. Nat Rev Drug Discov 2002; 1: 257–8PubMedGoogle Scholar
  2. 2.
    Kolanowski J. A risk-benefit assessment of anti-obesity drugs. Drug Saf 1999; 20: 119–31PubMedGoogle Scholar
  3. 3.
    Glazer G. Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety. Arch Intern Med 2001; 161: 1814–24PubMedGoogle Scholar
  4. 4.
    Haddock CK, Poston WSC, Dill PL, et al. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes 2002; 26: 262–73Google Scholar
  5. 5.
    Haiford JC. Clinical pharmacotherapy for obesity: current drugs and those in development. Curr Drug Targets 2004; 5: 637–46Google Scholar
  6. 6.
    National Institutes of Health, National Heart, Lung, and Blood Institute, North American Association for the Study of Obesity. The practical guide: identification, evaluation and treatment of overweight and obesity in adults. NIH Publication No. 00-4084, October 2000 [online]. Available from URL: http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_b.pdf [Accessed 2005 May 24]
  7. 7.
    Food and Drug Administration. Guidance for the clinical evaluation of weight-control drugs. Rockville (MD): FDA, 1996 Sep 24 [online]. Available from URL: http://www.fda.gov/ohrms/dockets/98fr/03d-0570-gd10001.pdf [Accessed 2005 May 24]
  8. 8.
    European Agency for the Evaluation of Medicinal Products. Note for guidance on clinical investigation of drugs used in weight control. CMP/EWP/281/96. London: The European Agency for the Evaluation of Medicinal Products, 1997 Dec 17 [online]. Available from URL: http://www.emea.eu.int/pdfs/human/ewp/028196en.pdf [Accessed 2005 May 24]
  9. 9.
    National Institutes of Health, National Heart, Lung, and Blood Institute, in cooperation with the National Institute of Diabetes and Digestive and Kidney Diseases. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. NIH Publication No. 98-4083. Washington, DC: US Government Press, 1998 Sep [online]. Available from URL: http://www.nhlbi.nih.gov [Accessed 2005 May 24]
  10. 10.
    Anti-obesity drugs guidance on appropriate prescribing and management. A report of a working party of the Nutrition Committee of the Royal College of Physicians. Online extract published 24 April 2003. Page last updated on May 9, 2005 [online]. Available from URL: http://www.rcplondon.ac.uk/news/news.asp?PR_id=171 [Accessed 2005 May 24]
  11. 11.
    Weintraub M. Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Clin Pharmacol Ther 1992; 51 Suppl.: 581–646PubMedGoogle Scholar
  12. 12.
    Wooltorton E. Obesity drug sibutramine (Meridia): hypertension and cardiac arrhythmias. CMAJ 2002; 166: 1307–8PubMedGoogle Scholar
  13. 13.
    Bray GA. A concise review on the therapeutics of obesity. Nutrition 2000; 16: 953–60PubMedGoogle Scholar
  14. 14.
    Clapham JC, Arch JRS, Tadayyon M. Anti-obesity drugs: a critical review of current therapies and future opportunities. Pharmacol Ther 2001; 89: 81–121PubMedGoogle Scholar
  15. 15.
    Cerulli J, Malone M. Outcomes of pharmacological and surgical treatment for obesity. Pharmacoeconomics 1998; 14: 269–83PubMedGoogle Scholar
  16. 16.
    Blundell JE, Lawton CL, Haiford JCG. Serotonin, eating behaviour and fat intake. Obes Res 1995; 3 Suppl. 3: 471–6Google Scholar
  17. 17.
    Wurtman JJ, Wurtman RJ, Reynolds S, et al. Fenfluramine suppresses snack intake among carbohydrate cravers but not among non-carbohydrate cravers. Int J Eat Disord 1987; 6: 687–99Google Scholar
  18. 18.
    Maher TJ, Ulus IH, Wurtman RJ. Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramine [letter]. Lancet 1999; 353(9146): 38PubMedGoogle Scholar
  19. 19.
    Seiler KU, Tamm G, Wassermann O. On the role of serotonin in the pathogenesis of pulmonary hypertension induced by anorectic drugs, an experimental study in the isolated, perfused rat lung. Clin Exp Pharmacol Physiol 1974; 1: 463–71Google Scholar
  20. 20.
    Munro JF, MacCuish AC, Wilson EM, et al. Comparison of continuous and intermittent anorectic therapy in obesity. BMJ 1968; 1: 352–4PubMedGoogle Scholar
  21. 21.
    Truant AP, Olon LP, Cobb S. Phentermine resin as an adjunct in medical weight reduction: a controlled, randomized, double-blind prospective study. Curr Ther Res Clin Exp 1972; 14: 726–38PubMedGoogle Scholar
  22. 22.
    Weintraub M, Hasday JD, Mushlin AI, et al. A double-blind clinical trial in weight control: use of fenfluramine and phentermine alone and in combination. Arch Intern Med 1984; 144: 1143–8PubMedGoogle Scholar
  23. 23.
    McKay RH. Long-term use of diethylpropion in obesity. Curr Med Res Opin 1973; 1: 489–93PubMedGoogle Scholar
  24. 24.
    DeRamos EC. The use of diethylpropion in the treatment of obesity. Br J Clin Pract 1964; 18: 210–1PubMedGoogle Scholar
  25. 25.
    Silverstone JT, Solomon T. The long-term management of obesity in general practice. Br J Clin Pract 1965; 19: 395–8PubMedGoogle Scholar
  26. 26.
    Le Riche WH, Csima A. A long-acting appetite suppressant drug studied for 24 weeks in both continuous and sequential administration. CMAJ 1967; 97: 1016–20Google Scholar
  27. 27.
    Greenway FL. Clinical studies with phenylpropanolamine: a metaanalysis. Am J Clin Nutr 1992; 55 (1 Suppl.): 203–5Google Scholar
  28. 28.
    Weintraub M, Ginsberg G, Stein EC, et al. Phenylpropanolamine OROS (Acutrim) vs placebo in combination with calorie restriction and physician-managed behavior modification. Clin Pharmacol Ther 1986; 39: 501–9PubMedGoogle Scholar
  29. 29.
    Greenway F, Herber D, Raum W, et al. Double-blind randomized placebo-controlled clinical trials with non-prescription medications in the treatment of obesity. Obes Res 1999; 7: 370–8PubMedGoogle Scholar
  30. 30.
    Enzi G, Baritussio A, Marchiori E, et al. Short-term and long-term clinical evaluation of a non-amphetaminic anorexiant (mazindol) in the treatment of obesity. J Int Med Res 1976; 4: 305–19PubMedGoogle Scholar
  31. 31.
    Inoue S. Clinical studies with mazindol. Obes Res 1995; 3 Suppl. 4: 549–52Google Scholar
  32. 32.
    Onishi T, Mazindol Research Group. Clinical evaluation of mazindol, an anorexiant on obesity [abstract]. Int J Obes 1990; 14: 34Google Scholar
  33. 33.
    Vernace BJ. Controlled comparative investigation of mazindol, D-amphetamine and placebo. Obesity Bariatric Med 1974; 3: 124–9Google Scholar
  34. 34.
    Allen GS. A double-blind clinical trial of diethylpropion hydrochloride, mazindol, and placebo in the treatment of exogenous obesity. Curr Ther Res 1977; 22: 678–85Google Scholar
  35. 35.
    Davis R, Faulds D. Dexfenfluramine: an updated review of its therapeutic use in the management of obesity. Drugs 1996; 52(2): 696–724PubMedGoogle Scholar
  36. 36.
    Guy-Grand B, Apfelbaum M, Crepaldi G, et al. International trial of long-term dexfenfluramine in obesity. Lancet 1989; II: 1142–5Google Scholar
  37. 37.
    Mathus-Vliegen EM, van de Voorde K, Kok AM, et al. Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour. J Intern Med 1992; 232: 119–27PubMedGoogle Scholar
  38. 38.
    Carvajal A, Garcia del Pozo J, Martin de Diego I, et al. Efficacy of fenfluramine and dexfenfluramine in the treatment of obesity: a meta-analysis. Methods Find Exp Clin Pharmacol 2000; 22: 285–90PubMedGoogle Scholar
  39. 39.
    Jones SP, Smith IG, Kelly F, et al. Long term weight loss with sibutramine [abstract]. Int J Obes Relat Metab Disord 1995; 19 Suppl. 2: 41Google Scholar
  40. 40.
    McMahon FG, Fujioka K, Singh BN, et al. Efficacy and safety of sibutramine in obese white and African-American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicentre trial. Arch Intern Med 2000; 160: 2185–91PubMedGoogle Scholar
  41. 41.
    Lean MEJ. Sibutramine: a review of clinical efficacy. Int J Obes Relat Metab Disord 1997; 21 Suppl. 1: S30–6PubMedGoogle Scholar
  42. 42.
    Smith IG, Jones SP, Heath MJ, et al. Categorical outcome analysis of weight loss in long-term sibutramine [abstract]. Int J Obes Relat Metab Disord 1996; 20: 157Google Scholar
  43. 43.
    Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res 1999; 7: 189–98PubMedGoogle Scholar
  44. 44.
    Smith IG, Goulder MA. Randomised placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. J Fam Pract 2001; 50: 505–12PubMedGoogle Scholar
  45. 45.
    McMahon FG, Weinstein SP, Rowe E, et al. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002; 16: 5–11PubMedGoogle Scholar
  46. 46.
    James WPT, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomized trial. Lancet 2000; 356: 2119–25PubMedGoogle Scholar
  47. 47.
    Apfelbaum M, Vague P, Ziegler O, et al. Long-term maintenance of weight loss after very-low-calorie diet: efficacy and tolerability of sibutramine. Am J Med 1999; 106: 179–84PubMedGoogle Scholar
  48. 48.
    Bray GA, Ryan DH, Gordon D, et al. A double blind randomized placebo-controlled trial of sibutramine. Obes Res 1996; 4: 263–70PubMedGoogle Scholar
  49. 49.
    Fanghanel G, Cortinas L, Sanchez-Reyses L, et al. A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity. Int J Obes 2000; 24: 150–5Google Scholar
  50. 50.
    Cuellar GEM, Ruiz AM, Monsalve MC, et al. Six-month treatment of obesity with sibutramine 15mg: a double-blind, placebo-controlled monocentre clinical trial in a Hispanic population. Obes Res 2000; 8: 71–82PubMedGoogle Scholar
  51. 51.
    Wirth A, Krause J. Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 2001; 286: 1331–9PubMedGoogle Scholar
  52. 52.
    Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 2004; 164: 994–1003PubMedGoogle Scholar
  53. 53.
    Arterburn D, Noël PH. Obesity: extracts from clinical evidence. BMJ 2001; 321: 1406–9Google Scholar
  54. 54.
    McTigue KM, Harris R, Hemphill B, et al. Screening and interventions for obesity in adults: summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2003; 139: 933–49PubMedGoogle Scholar
  55. 55.
    Padwal R, Li SK. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes Relat Metab Disord 2003; 27: 1437–46PubMedGoogle Scholar
  56. 56.
    Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight: Cochrane Metabolic and Endocrine Disorders Group. Cochrane Database Syst Rev 2005; (2): CD004094Google Scholar
  57. 57.
    Wadden TA, Berkowitz RI, Sarwer DB, et al. Benefits of lifestyle modification in the pharmacologic treatment of obesity. Arch Intern Med 2001; 161: 218–27PubMedGoogle Scholar
  58. 58.
    Hauner H, Meier M, Jockel KH, et al. Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein beta3 subunit gene (GNB3) C825T polymorphism. Pharmacogenetics 2003; 13: 453–9PubMedGoogle Scholar
  59. 59.
    Berkowitz RI, Wadden TA, Tershakovec AM, et al. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. JAMA 2003; 289(14): 1805–12PubMedGoogle Scholar
  60. 60.
    Godoy-Matos A, Carraro L, Vieira A, et al. Treatment of obese adolescents with sibutramine: a randomised double-blind controlled study. J Clin Endocrinol Metab 2005; 90: 1460–5PubMedGoogle Scholar
  61. 61.
    Hanotin C, Thomas F, Jones SP, et al. A comparison of sibutramine and dexfenfluramine in the treatment of obesity. Obes Res 1998; 6: 285–91PubMedGoogle Scholar
  62. 62.
    Wadden TA, Berkowitz RI, Womble LG, et al. Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 2000; 6: 431–7Google Scholar
  63. 63.
    Aydin N, Topsever P, Kaya A, et al. Orlistat, sibutramine, or combination therapy: which performs better on waist circumference in relation with body mass index in obese patients? Tohoku J Exp Med 2004; 202: 173–80PubMedGoogle Scholar
  64. 64.
    McNeely W, Goa KL. Sibutramine: a review of its contribution to the management of obesity. Drugs 1998; 56(6): 1093–124PubMedGoogle Scholar
  65. 65.
    Heine RJ. Drug therapy for management of obesity [letter]. Lancet 2001; 357: 1287PubMedGoogle Scholar
  66. 66.
    Hazenberg BP. Randomized, double-blind, placebo-controlled, multicenter study of sibutramine in obese hypertensive patients. Cardiology 2000; 94: 152–8PubMedGoogle Scholar
  67. 67.
    Scholze J. Sibutramine in clinical practice: a PMS-study with positive effects on blood pressure and metabolic parameters. Dtsche Med Wochenschr 2002; 127: 606–10Google Scholar
  68. 68.
    Kim SH, Lee YM, Jee SH, et al. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–23PubMedGoogle Scholar
  69. 69.
    Zannad F, Gille B, Grentzinger A, et al. Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction. Am Heart J 2002; 144: 508–15PubMedGoogle Scholar
  70. 70.
    Nisoli E, Carruba MO. A benefit-risk assessment of sibutramine in the management of obesity. Drug Saf 2003; 26: 1027–48PubMedGoogle Scholar
  71. 71.
    Hauptman J, Lucas C, Boldrin MN, et al. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med 2000; 9: 160–7PubMedGoogle Scholar
  72. 72.
    Sjöström L, Rissanen A, Anderson T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients: European Multicentre Orlistat Study Group. Lancet 1998; 352: 167–73PubMedGoogle Scholar
  73. 73.
    Heymsfield SB, Segal KR, Hauptman J, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med 2000; 160(9): 1321–6PubMedGoogle Scholar
  74. 74.
    Rossner S, Sjostrom L, Noack R, et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity: European Orlistat Obesity Study Group. Obes Res 2000; 8: 49–61PubMedGoogle Scholar
  75. 75.
    Torgerson JA, Hauptman J, Boldrin MN, et al. XENical in the prevention of Diabetes in Obese Subjects (XENDOS) study. Diabetes Care 2004; 27: 155–61PubMedGoogle Scholar
  76. 76.
    Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care 1998; 21: 1288–94PubMedGoogle Scholar
  77. 77.
    Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA 1999; 281: 235–42PubMedGoogle Scholar
  78. 78.
    Hill JO, Hauptman J, Anderson JW, et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Am J Clin Nutr 1999; 69: 1108–16PubMedGoogle Scholar
  79. 79.
    Lindgarde F, on behalf of Orlistat Swedish Multimorbidity Study. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. J Intern Med 2000; 248: 245–54PubMedGoogle Scholar
  80. 80.
    Finer N, James WP, Kopelman PG, et al. 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: 306–13PubMedGoogle Scholar
  81. 81.
    Reaven G, Segal K, Hauptman J, et al. Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X. Am J Cardiol 2001; 87: 827–31PubMedGoogle Scholar
  82. 82.
    Broom I, Wilding J, Stott P, et al. Randomised trial of the effect of orlistat on body weight and cardiovascular disease risk profile in obese patients: the UK Multimorbidity Study. The UK Multimorbidity Study Group. Int J Clin Pract 2002; 56: 494–9Google Scholar
  83. 83.
    O’Meara S, Riemsma R, Shirran L, et al. A systematic review of the clinical effectiveness of orlistat used for the management of obesity. Obes Rev 2004; 5: 51–68PubMedGoogle Scholar
  84. 84.
    Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532–46PubMedGoogle Scholar
  85. 85.
    Hutton B, Fergusson D. Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. Am J Clin Nutr 2004; 80: 1461–8PubMedGoogle Scholar
  86. 86.
    Leung WY, Neil TG, Chan JC, et al. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther 2003; 25: 58–80PubMedGoogle Scholar
  87. 87.
    Norgren S, Danielsson P, Jurold R, et al. Orlistat treatment in obese prepubertal children: a pilot study. Acta Paediatr 2003; 92: 666–70PubMedGoogle Scholar
  88. 88.
    McDuffie JR, Calis KA, Uwaifo GI, et al. Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. Obes Res 2002; 10: 642–50PubMedGoogle Scholar
  89. 89.
    Ozkan B, Bereket A, Turan S, et al. Addition of orlistat to conventional treatment in adolescents with severe obesity. Eur J Pediatr 2004; 163: 738–41PubMedGoogle Scholar
  90. 90.
    Roche: investor update. FDA approves labeling for use of Xenical (orlistat) in management of obesity in adolescent patients aged 12 to 16 years. Basel, 16 December 2003 [online]. Available from URL: http://www.roche.com/home/investors/inv_news_upd/inv_news_upd_2003/inv-update-2003-12-16a.htm?printout=l [Accessed 2005 May 24]
  91. 91.
    Clinical review: executive summary section. Clinical review for NDA 20-766/S-018. 5 December 2003 [online]. Available from URL: http://www.fda.gov/cder/foi/esum/2003/20766 se5-018_Orlistat_BPCA_CLINICAL_ltr.pdf [Accessed 2005 May 24]
  92. 92.
    Gokcel A, Gumurdulu Y, Karakose H, et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obes Metab 2002; 4(1): 49–55PubMedGoogle Scholar
  93. 93.
    Derosa G, Mugellini A, Ciccarelli L, et al. Effects of orlistat, simvastatin, and orlistat + simvastatin in obese patients with hypercholesterolaemia: a randomized open label trial. Curr Ther Res 2002; 63: 621–33Google Scholar
  94. 94.
    Derosa G, Mugellini A, Ciccarelli L, et al. Randomised double-blind placebo-controlled comparison of the action of orlistat, fluvastatin or both on anthropometric measurements blood pressure and lipid profile in obese patients with hypercholesterolemia prescribed a standard diet. Clin Ther 2003; 25: 1107–22PubMedGoogle Scholar
  95. 95.
    James WPT, Avenell A, Broom J, et al. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes 1997; 21 Suppl. 3: 24–30Google Scholar
  96. 96.
    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 Pharmacol 1996; 36: 647–53PubMedGoogle Scholar
  97. 97.
    Levine LR, Enas GG, Thompson WL, et al. Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study. Int J Obes Relat Metab Disord 1989; 13: 635–45Google Scholar
  98. 98.
    Bray GA. Use and abuse of appetite-suppressant drugs in the treatment of obesity. Ann Intern Med 1993; 119: 707–13PubMedGoogle Scholar
  99. 99.
    Goldstein DJ, Rampey AH, Enas GG, et al. Fluoxetine: a randomized clinical trial in the treatment of obesity. Int J Obes Relat Metab Disord 1994; 18: 129–35PubMedGoogle Scholar
  100. 100.
    Darga LL, Carroll-Michals L, Botsford SJ, et al. Fluoxetine’s effect on weight loss in obese subjects. Am J Clin Nutr 1991; 54: 321–5PubMedGoogle Scholar
  101. 101.
    Anderson JW, Greenway FL, Fujioka K, et al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res 2002; 10: 633–41PubMedGoogle Scholar
  102. 102.
    Jain AK, Kaplan RA, Gadde KM, et al. Bupropion SR vs placebo for weight loss in obese patients with depressive symptoms. Obes Res 2002; 10: 1049–56PubMedGoogle Scholar
  103. 103.
    Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11: 722–33PubMedGoogle Scholar
  104. 104.
    Wilding J, Van Gaal L, Rissanen A, et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects: the OBES-002 Study Group. Int J Obes 2004; 28: 1399–410Google Scholar
  105. 105.
    Astrup A, Caterson I, Zelissen P, et al. Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects. Obes Res 2004; 12: 1658–69PubMedGoogle Scholar
  106. 106.
    Gadde KM, Franciscy DM, Wagner II HR, et al. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 2003; 289: 1820–5PubMedGoogle Scholar
  107. 107.
    Pedrinola F, Sztejnsznajd C, Lima N, et al. The addition of dexfenfluramine to fluoxetine in the treatment of obesity: a randomized clinical trial. Obes Res 1996; 4: 549–54PubMedGoogle Scholar
  108. 108.
    Dhurandhar NV, Atkinson RL. Comparison of serotonin agonists in combination with phentermine for treatment of obesity [abstract]. FASEB J 1996; 10: A561Google Scholar
  109. 109.
    Anchors M. Fluoxetine is a safer alternative to fenfluramine in the medical treatment of obesity [letter]. Arch Intern Med 1997; 157: 1270PubMedGoogle Scholar
  110. 110.
    Griffen L, Anchors M. The “Phen-Pro” diet drug combination is not associated with valvular heart disease. Arch Intern Med 1998; 158: 1278–9PubMedGoogle Scholar
  111. 111.
    Gadde KM, Krishnan KRK, Logue EJ, et al. Bupropion SR shows promise as an effective obesity treatment [abstract]. Obes Res 1997; 5 Suppl. 1: 51Google Scholar
  112. 112.
    Croft H, Houser T, Leadbetter R, et al. Effect of bupropion SR on weight in the long-term treatment of depression [abstract]. Obes Res 2000; 8 Suppl. 1: 10Google Scholar
  113. 113.
    Gadde KM, Parker CB, Maner LG, et al. Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Obes Res 2001; 9: 544–51PubMedGoogle Scholar
  114. 114.
    Malchow-Moller A, Larsen S, Hey H, et al. Ephedrine as an anorectic: the story of the ‘Elsinore pill’. Int J Obes 1981; 5: 183–7PubMedGoogle Scholar
  115. 115.
    Liu YL, Toubro S, Astrup A, et al. Contribution of β3-adrenoceptor activation to ephedrine-induced thermogenesis in humans. Int J Obes 1995; 19: 678–85Google Scholar
  116. 116.
    Stock MJ. Potential for β3-adrenoceptor agonists in the treatment of obesity. Int J Obes 1996; 20 Suppl. 4: 4–5Google Scholar
  117. 117.
    Astrup AV, Breum L, Toubro S, et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: a double blind trial. Int J Obes Relat Metab Disord 1992; 16: 269–77PubMedGoogle Scholar
  118. 118.
    Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev 2001; 2: 199–211PubMedGoogle Scholar
  119. 119.
    Toubro S, Astrup A, Breum L, et al. The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans. Int J Obes Relat Metab Disord 1993; 17 Suppl. 3: S73–7, S82PubMedGoogle Scholar
  120. 120.
    Breum L, Pedersen JK, Ahlstrom F, et al. Comparison of an ephedrine/caffeine combination and dexfenfluramine in treatment of obesity: a double-blind multi-centre trial in general practice. Int J Obes Relat Metab Disord 1994; 18: 99–103PubMedGoogle Scholar
  121. 121.
    Molnar D, Torok K, Erhardt E, et al. Safety and efficacy of treatment with an ephedrine/caffeine mixture: the first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord 2000; 24: 1573–8PubMedGoogle Scholar
  122. 122.
    Boozer CN, Daly PA, Homel P, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord 2002; 26: 593–604PubMedGoogle Scholar
  123. 123.
    Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance. JAMA 2003; 289: 1537–45PubMedGoogle Scholar
  124. 124.
    Bays H, Dujovne C. Pharmacotherapy of obesity: currently marketed and upcoming agents. Am J Cardiovasc Drugs 2002; 2: 245–53PubMedGoogle Scholar
  125. 125.
    Bays HE. Current and investigational antiobesity agents and obesity therapeutic treatment targets. Obes Res 2004; 12: 1197–211PubMedGoogle Scholar
  126. 126.
    Larsen TM, Toubro S, van Baak MA, et al. Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr 2002; 76: 780–8PubMedGoogle Scholar
  127. 127.
    Hu B, Jennings LL. Orally bioavailable β3-adrenergic receptor agonists as potential therapeutic agents for obesity and type-II diabetes. Prog Med Chem 2003; 41: 167–94PubMedGoogle Scholar
  128. 128.
    Nisoli E, Tonello C, Carruba MO. Beta3-adrenergic receptors: really relevant targets for anti-obesity drugs? Curr Med Chem Central Nervous System Agents 2003; 3: 257–73Google Scholar
  129. 129.
    Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003; 349: 941–8PubMedGoogle Scholar
  130. 130.
    Cohen MA, Ellis SM, Le Roux CW, et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 2003; 88: 4696–701PubMedGoogle Scholar
  131. 131.
    Wilding J. AOD-9604 metabolic. Curr Opin Investig Drugs 2004; 5: 436–40PubMedGoogle Scholar
  132. 132.
    Obesity drug codenamed AOD9604 highly successful in trials. Pharmaceutical News Published: Thursday, 16-Dec-2004 [online]. Available from URL: http://www.news-medical.net/print_article.asp?id=6878 [Accessed 2005 May 24]
  133. 133.
    Heffernan M, Summers RJ, Thorburn A, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knock-out mice. Endocrinology 2001; 142: 5182–9PubMedGoogle Scholar
  134. 134.
    Habeck M. A succulent cure to end obesity. Drug Discov Today 2002; 7: 280–1PubMedGoogle Scholar
  135. 135.
    Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–5PubMedGoogle Scholar
  136. 136.
    Proietto J, Thorburn AW. The therapeutic potential of leptin. Expert Opin Investig Drugs 2003; 12: 373–8PubMedGoogle Scholar
  137. 137.
    Bell-Anderson KS, Bryson JM. Leptin as a potential treatment for obesity. Treat Endocrinol 2004; 3: 11–8PubMedGoogle Scholar
  138. 138.
    Heymsfield SB, Greenberg AS, Fuujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized controlled dose escalation trial. JAMA 1999; 282: 1568–75PubMedGoogle Scholar
  139. 139.
    Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized dose-ranging study. JAMA 2003; 289: 1826–32PubMedGoogle Scholar
  140. 140.
    Van Gaal LF, Rissanen AM, Scheen AJ, et al., for the RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–97PubMedGoogle Scholar
  141. 141.
    Ben-Menachem E, Axelsen M, Johanson EH, et al. Predictors of weight loss in adults with topiramate-treated epilepsy. Obes Res 2003; 11: 556–62PubMedGoogle Scholar
  142. 142.
    Oommen KJ. Zonisamide: a new antiepileptic drug. Clin Neuropharmacol 1999; 22: 192–200PubMedGoogle Scholar
  143. 143.
    Hadjikoutis S, Pickersgill TP, Smith PEM. Drug points: weight loss associated with levetiracetam. BMJ 2003; 327: 905PubMedGoogle Scholar
  144. 144.
    Gidal BE, Sheth RD, Magnus L, et al. Levetiracetam does not alter body weight: analysis of randomized, controlled clinical trials. Epilepsy Res 2003; 56: 121–6PubMedGoogle Scholar
  145. 145.
    Houri M, Pratley RE. Rimonabant: a novel treatment for obesity and the metabolic syndrome. Curr Diab Rep 2005; 5: 43–4Google Scholar
  146. 146.
    New study confirms benefit of rimonabant in weight loss, waist circumference and metabolic risk factor improvement. European Society of Cardiology Congress, 2004 Aug 29 [online]. Available from URL: http://www.sanofi-synthelabo.us/index.html [Accessed 2005 Feb 10]
  147. 147.
    Results from RIO-North America trial show that first year improvements in cardiovascular risk factors maintained in the second year of treatment. American Society of Cardiology Congress, 2004 Nov 9 [online]. Available from URL: http://www.sanofi-synthelabo.us/index.html [Accessed 2005 Feb10]
  148. 148.
    Norris SL, Zhan X, Avenell A, et al. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2004; 164: 1395–404PubMedGoogle Scholar
  149. 149.
    US Preventive Services Task Force. Screening for obesity in adults: recommendations and rationale. Ann Intern Med 2003; 139: 930–2Google Scholar
  150. 150.
    Wirth A. Reduction of body weight and co-morbidities by orlistat: the XXL-Primary Health Care Trial. Diabetes Obes Metab 2005; 7: 21–7PubMedGoogle Scholar
  151. 151.
    Muls E, Kolanowski J, Scheen A, et al. The effects of orlistaton weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo controlled, multicentre study. The ObelHyx Study Group. Int J Obes 2001; 25: 1713–21Google Scholar
  152. 152.
    Kiortsis DN, Filippatos TD, Elisat MS. The effects of orlistat on metabolic parameters and other cardiovascular risk factors. Diabetes Metab 2005; 31: 15–22PubMedGoogle Scholar
  153. 153.
    Swinburn BA, Carey D, Hills AP, et al. Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes Obes Metab 2005; 7: 254–62PubMedGoogle Scholar
  154. 154.
    Vettor R, Pagano C, Serra R, et al. Effect of sibutramine on weight management and metabolic control in type 2 diabetes: a meta-analysis. Diabetes Care 2005; 28: 942–9PubMedGoogle Scholar
  155. 155.
    Curran MP, Scott LJ. Orlistat: a review of its use in the management of patients with obesity. Drugs 2004; 64(24): 2845–64PubMedGoogle Scholar
  156. 156.
    Gupta S. Fat pill for teens: xenical may have the FDA’s blessing, but is it a good idea? Time 2003 Dec 29-2004 Jan 5; 162(26): 162PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Lisa L. Ioannides-Demos
    • 1
  • Joseph Proietto
    • 2
  • John J. McNeil
    • 1
  1. 1.Department of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia
  2. 2.Department of MedicineUniversity of Melbourne, Repatriation HospitalMelbourneAustralia

Personalised recommendations