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.

  • Review Article
  • Published:

Drug Insight: appetite suppressants

Abstract

The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the γ-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine—so named because they mimic many effects of norepinephrine—are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine–5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: A model of hypothalamic mechanisms controlling feeding.

Similar content being viewed by others

References

  1. Bray GA and Greenway FL (1999) Current and potential drugs for treatment of obesity. Endocr Rev 20: 805–875

    Article  CAS  Google Scholar 

  2. Bray GA and Tartaglia LA (2000) Medicinal strategies in the treatment of obesity. Nature 404: 672–677

    Article  CAS  Google Scholar 

  3. Kroeze WK et al. (2003) H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28: 519–526

    Article  CAS  Google Scholar 

  4. Sykas SL et al. (1983) Anorectic drugs which stimulate thermogenesis. Life Sci 33: 1269–1275

    Article  Google Scholar 

  5. Lupien JR and Bray GB (1986) Effect of mazindol, d-amphetamine and diethylpropion on purine nucleotide binding to brown adipose tissue. Pharmacol Biochem Behav 25: 733–738

    Article  CAS  Google Scholar 

  6. Hansen DL et al. (1998) Thermogenic effects of sibutramine in humans. Am J Clin Nutr 68: 1180–1186

    Article  CAS  Google Scholar 

  7. Scoville BA (1975) Review of amphetamine-like drugs by the Food and Drug Administration: clinical data and value judgments. In Obesity in Perspective. (Ed. Bray GA) Washington DC: Department of Health, Education, and Welfare Publication NIH 75–708, 441–443

    Google Scholar 

  8. Munro JF et al. (1968) Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1: 352–354

    Article  CAS  Google Scholar 

  9. Haddock CK et al. (2002) Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord 26: 262–273

    Article  CAS  Google Scholar 

  10. Padwal R et al. (2003) Long-term pharmacotherapy for obesity and overweight: a systematic review and meta-analysis of randomized controlled trials. Int J Obes Relat Metab Disord 27: 1437–1446

    Article  CAS  Google Scholar 

  11. Bray GA et al. (1999) Sibutramine produces dose-related weight loss. Obes Res 7: 189–198

    Article  CAS  Google Scholar 

  12. James WPT et al. (2000) Effect of sibutramine on weight maintenance after weight loss: a randomized trial. STORM study group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 356: 2119–2125

    Article  CAS  Google Scholar 

  13. Wirth A and Krause J (2001) Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 286: 1331–1339

    Article  CAS  Google Scholar 

  14. McMahon FG et al. (2000) Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled multicenter trial. Arch Intern Med 160: 2185–2191

    Article  CAS  Google Scholar 

  15. McMahon FG et al. (2002) Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 16: 5–11

    Article  CAS  Google Scholar 

  16. Hazenberg BP (2000) Randomized, double-blind, placebo-controlled, multicenter study of sibutramine in obese hypertensive patients. Cardiology 94: 152–158

    Article  CAS  Google Scholar 

  17. Sramek, JJ et al. (2002) Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomized trial. J Hum Hypertens 16: 13–19

    Article  CAS  Google Scholar 

  18. Wadden RA et al. (2001) Benefits of lifestyle modification in the pharmacologic treatment of obesity: a randomized trial. Arch Intern Med 161: 218–227

    Article  CAS  Google Scholar 

  19. Ascher JA et al. (1995) Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 56: 395–401

    CAS  PubMed  Google Scholar 

  20. Anderson JW et al. (2002) Bupropion SR significantly enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res 10: 633–641

    Article  CAS  Google Scholar 

  21. Guy-Grand B et al. (1989) International trial of long-term dexfenfluramine in obesity. Lancet 2: 1142–1145

    Article  CAS  Google Scholar 

  22. Weintraub M et al. (1984) A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination. Arch Intern Med 144: 1143–1148

    Article  CAS  Google Scholar 

  23. Connolly HM et al. (1997) Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 337: 581–588

    Article  CAS  Google Scholar 

  24. Bray GA et al. (2003) A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 11: 722–733

    Article  CAS  Google Scholar 

  25. Wilding J et al. (2004) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes Relat Metab Disord 28: 1399–1410

    Article  CAS  Google Scholar 

  26. Gadde KM et al. (2003) Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 289: 1820–1825

    Article  CAS  Google Scholar 

  27. Di Marzo V et al. (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410: 822–825

    Article  CAS  Google Scholar 

  28. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA (2001) 285: 2486–2497

  29. Cohen C et al. (2002) SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol 2002 13: 451–463

    Article  CAS  Google Scholar 

  30. Farooqi IS et al. (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341: 879–884

    Article  CAS  Google Scholar 

  31. Considine RV et al. (1995) Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest 95: 2986–2988

    Article  CAS  Google Scholar 

  32. Friedman JM (2002) The function of leptin in nutrition, weight, and physiology. Nutr Rev 60 (Part 2): S1–S14

    Article  Google Scholar 

  33. Morton GJ and Schwartz MW (2001) The NPY/AgRP neuron and energy homeostasis. Int J Obes Relat Metab Disord 25 (Suppl 5): S56–62

    Article  Google Scholar 

  34. Heymsfield SB et al. (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282: 1568–1575

    Article  CAS  Google Scholar 

  35. Lambert PD et al. (2001) Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. Proc Nat Acad Sci USA 98: 4652–4657

    Article  CAS  Google Scholar 

  36. Ettinger MP et al. (2003) Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study. JAMA 289: 1826–1832

    Article  CAS  Google Scholar 

  37. Regeneron Pharmaceuticals (online 14 April 2003) Regeneron's AXOKINE® promotes weight loss in study of overweight and obese people with type 2 diabetes [http://www.regeneron.com/company/press_detail.asp?v_c_id=170] (accessed 23 December 2004)

  38. Palmiter RD et al. (1998) Life without neuropeptide Y. Recent Prog Horm Res 53: 163–199

    CAS  PubMed  Google Scholar 

  39. Ludwig DS et al. (1998) Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus. Am J Physiol 274 (Part 1): E627–E633

    CAS  PubMed  Google Scholar 

  40. Ludwig DS et al. (2001) Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107: 379–386

    Article  CAS  Google Scholar 

  41. Shimada M et al. (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396: 670–674

    Article  CAS  Google Scholar 

  42. Huszar D et al. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88: 131–141

    Article  CAS  Google Scholar 

  43. Fehm HL et al. (2001) The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans. J Clin Endocrinol Metab 86: 1144–1148

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George A Bray.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bray, G. Drug Insight: appetite suppressants. Nat Rev Gastroenterol Hepatol 2, 89–95 (2005). https://doi.org/10.1038/ncpgasthep0092

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpgasthep0092

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing