Current Obesity Reports

, Volume 3, Issue 3, pp 361–367 | Cite as

Anti-Obesity Agents and the US Food and Drug Administration

Hot Topic


Despite the growing market for obesity care, the US Food and Drug Administration (FDA) has approved only two new pharmaceutical agents—lorcaserin and combination phentermine/topiramate—for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA’s history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model.


Obesity Weight-loss drugs Weight management Anti-obesity policy FDA 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307(5):491–7. doi:10.1001/jama.2012.39.PubMedCrossRefGoogle Scholar
  2. 2.
    Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA. 2012;307(5):483–90. doi:10.1001/jama.2012.40.PubMedCrossRefGoogle Scholar
  3. 3.
    CDC. Obesity: halting the epidemic by making health easier. 2011.Google Scholar
  4. 4.
    Ogden CLC. Prevalence of overweight, obesity, and extreme obesity among adults: United States, trends 1960–1962 through 2007–2008. In: Statistics NCfH, editor. 2010.Google Scholar
  5. 5.
    Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341(6):427–34. doi:10.1056/NEJM199908053410607.PubMedCrossRefGoogle Scholar
  6. 6.
    Deslypere JP. Obesity and cancer. Metab Clin Exp. 1995;44(9 Suppl 3):24–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Grundy SM, Barnett JP. Metabolic and health complications of obesity. Dis Mon. 1990;36(12):641–731.PubMedGoogle Scholar
  8. 8.
    Wilson PW, D'Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162(16):1867–72.PubMedCrossRefGoogle Scholar
  9. 9.
    Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff. 2009;28(5):w822–31. doi:10.1377/hlthaff.28.5.w822.CrossRefGoogle Scholar
  10. 10.
    Weintraub M. Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Clin Pharmacol Ther. 1992;51(5):581–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Devereux RB. Appetite suppressants and valvular heart disease. N Engl J Med. 1998;339(11):765–6. doi:10.1056/NEJM199809103391109.PubMedCrossRefGoogle Scholar
  12. 12.
    Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, Maggioni A, et al. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial. Eur Heart J. 2007;28(23):2915–23. doi:10.1093/eurheartj/ehm217.PubMedCrossRefGoogle Scholar
  13. 13.
    Samat A, Tomlinson B, Taheri S, Thomas GN. Rimonabant for the treatment of obesity. Recent Patents Cardiovasc Drug Discov. 2008;3(3):187–93.CrossRefGoogle Scholar
  14. 14.
    Li MF, Cheung BM. Rise and fall of anti-obesity drugs. World J Diabetes. 2011;2(2):19–23. doi:10.4239/wjd.v2.i2.19.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction. 2009;104(7):1085–99. doi:10.1111/j.1360-0443.2009.02564.x.PubMedCrossRefGoogle Scholar
  16. 16.
    Frohmader KS, Pitchers KK, Balfour ME, Coolen LM. Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models. Horm Behav. 2010;58(1):149–62. doi:10.1016/j.yhbeh.2009.11.009.PubMedCrossRefGoogle Scholar
  17. 17.
    Bays HE. Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development. Expert Rev Cardiovasc Ther. 2011;9(3):265–77. doi:10.1586/erc.10.22.PubMedCrossRefGoogle Scholar
  18. 18.
    FDA. BELVIQ (lorcaserin hydrochloride) tablets, for oral use Initial U.S. Approval: 2012. 2012.Google Scholar
  19. 19.
    Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA's assessment of two drugs for chronic weight management. N Engl J Med. 2012;367(17):1577–9. doi:10.1056/NEJMp1211277.PubMedCrossRefGoogle Scholar
  20. 20.
    Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for obesity: past, current, and future therapies. J Obes. 2011;2011:179674. doi:10.1155/2011/179674.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    FDA. QSYMIA (phentermine and topiramate extended-release) capsules, for oral use, CIV Initial U.S. Approval: 2012. 2012.Google Scholar
  22. 22.
    Margulis AV, Mitchell AA, Gilboa SM, Werler MM, Mittleman MA, Glynn RJ, et al. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol. 2012;207(5):405 e1-7. doi:10.1016/j.ajog.2012.07.008.PubMedCrossRefGoogle Scholar
  23. 23.
    CDER. Draft guidance for industry on developing products for weight management. 2007.Google Scholar
  24. 24.
    Douketis JD, Macie C, Thabane L, Williamson DF. Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice. Int J Obes. 2005;29(10):1153–67. doi:10.1038/sj.ijo.0802982.CrossRefGoogle Scholar
  25. 25.
    Ledford H. Heart studies needed for obesity drugs, FDA advisers say. Nature [online]. 2012.Google Scholar
  26. 26.
    Morrato EH, Allison DB. FDA approval of obesity drugs: a difference in risk-benefit perceptions. JAMA. 2012;308(11):1097–8. doi:10.1001/jama.2012.10007.PubMedCrossRefGoogle Scholar
  27. 27.
    Hendricks EJ. Should the FDA approval process for weight-loss drugs be modified? AJHP Off J Am Soc Health Syst Pharm. 2011;68(21):2094–5. doi:10.2146/ajhp110228.CrossRefGoogle Scholar
  28. 28.•
    Dietrich MO, Horvath TL. Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons. Nat Rev Drug Discov. 2012. doi:10.1038/nrd3739. An in-depth review of risks-benefits of currently available anti-obesity agents, limitations in our pathophysiological understanding obestiy, and potential future tartgets for anti-obesity agents.PubMedGoogle Scholar
  29. 29.
    Jeffery RW, Drewnowski A, Epstein LH, Stunkard AJ, Wilson GT, Wing RR, et al. Long-term maintenance of weight loss: current status. Health Psychol Off J Div Health Psychol Am Psychol Assoc. 2000;19(1 Suppl):5–16.Google Scholar
  30. 30.
    Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM. Meta-analysis: the effect of dietary counseling for weight loss. Ann Intern Med. 2007;147(1):41–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Long-term pharmacotherapy in the management of obesity. National Task Force on the Prevention and Treatment of Obesity. JAMA. 1996;276(23):1907–15.Google Scholar
  32. 32.
    Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity. 2011;19(12):2351–60. doi:10.1038/oby.2011.94.PubMedCrossRefGoogle Scholar
  33. 33.
    Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev. 2004;3, CD004094. doi:10.1002/14651858.CD004094.pub2.PubMedGoogle Scholar
  34. 34.
    Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther. 2011;90(1):40–51. doi:10.1038/clpt.2011.82.PubMedCrossRefGoogle Scholar
  35. 35.
    Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245–56. doi:10.1056/NEJMoa0909809.PubMedCrossRefGoogle Scholar
  36. 36.
    Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96(10):3067–77. doi:10.1210/jc.2011-1256.PubMedCrossRefGoogle Scholar
  37. 37.
    O'Neil PM, Smith SR, Weissman NJ, Fidler MC, Sanchez M, Zhang J, et al. Randomized placebo-controlled clinical trial of Lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM Study. Obesity. 2012;20(7):1426–36. doi:10.1038/oby.2012.66.PubMedCrossRefGoogle Scholar
  38. 38.
    Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–52. doi:10.1016/S0140-6736(11)60205-5.PubMedCrossRefGoogle Scholar
  39. 39.•
    Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20(2):330–42. doi:10.1038/oby.2011.330. The most recent clinical trial of the newly approved combination phentermine/topiramate agent, reflecting the current standards the FDA has for new, anti-obesity drug applications.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Vivus. Results from phase 3 EQUATE trial of VIVUS' Qnexa highlighted at European Congress on Obesity. 2009.Google Scholar
  41. 41.
    Roberts Jr TG, Lynch Jr TJ, Chabner BA. The phase III trial in the era of targeted therapy: unraveling the "go or no go" decision. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21(19):3683–95. doi:10.1200/JCO.2003.01.204.CrossRefGoogle Scholar
  42. 42. Method-of-use study assessing the effect of naltrexone sustained release (SR)/ bupropion SR on body weight and cardiovascular risk factors in overweight and obese subjects.Google Scholar
  43. 43.
    Berry DA. Bayesian clinical trials. Nat Rev Drug Discov. 2006;5(1):27–36. doi:10.1038/nrd1927.PubMedCrossRefGoogle Scholar
  44. 44.
    FDA. 2012 Materials of the gastroenterology-urology devices panel. Obes Panel Pack. 2012.Google Scholar
  45. 45.
    Bays H. Perspective: is bias behind the lack of new obesity drug therapies? Clin Endocrinol News. 2010;5(8):10.Google Scholar
  46. 46.
    Ding D, Gebel K. Built environment, physical activity, and obesity: what have we learned from reviewing the literature? Health Place. 2012;18(1):100–5. doi:10.1016/j.healthplace.2011.08.021.PubMedCrossRefGoogle Scholar
  47. 47.
    FDA. Consumer updates: medications target long-term weight control. 2012.Google Scholar
  48. 48.
    Avorn J. Interview with Dr. Jerry Avorn on the FDA's recent approval of two weight loss drugs. N Engl J Med. 2012;367:633–5.CrossRefGoogle Scholar
  49. 49.
    Mechanick JI, Garber AJ, Handelsman Y, Garvey WT. American Association of Clinical Endocrinologists' position statement on obesity and obesity medicine. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinologists. 2012;18(5):642–8. doi:10.4158/EP12160.PS.Google Scholar
  50. 50.••
    AMA. American Medical Association House of Delegates Resolution 420: recognition of obesity as a disease. 2013. Available at: [Accessed January 2014]. This document outlines the various reasons why the American Medical Association and American Association of Clinical Endocrinology have recategorized obesity as a primary disease, underscoring the importance to expand the number of available therapeutic options.
  51. 51.
    Allison DB, Downey M, Atkinson RL, Billington CJ, Bray GA, Eckel RH, et al. Obesity as a disease: a white paper on evidence and arguments commissioned by the Council of the Obesity Society. Obesity. 2008;16(6):1161–77. doi:10.1038/oby.2008.231.PubMedCrossRefGoogle Scholar
  52. 52.
    Joshi SR, Mohan V, Joshi SS, Mechanick JI, Marchetti A. Transcultural diabetes nutrition therapy algorithm: the Asian Indian application. Curr Diabetes Rep. 2012;12(2):204–12. doi:10.1007/s11892-012-0260-0.CrossRefGoogle Scholar
  53. 53.
    Mechanick JI, Marchetti AE, Apovian C, Benchimol AK, Bisschop PH, Bolio-Galvis A, et al. Diabetes-specific nutrition algorithm: a transcultural program to optimize diabetes and prediabetes care. Curr Diabetes Rep. 2012;12(2):180–94. doi:10.1007/s11892-012-0253-z.CrossRefGoogle Scholar
  54. 54.
    Su HY, Tsang MW, Huang SY, Mechanick JI, Sheu WH, Marchetti A, et al. Transculturalization of a diabetes-specific nutrition algorithm: Asian application. Curr Diabetes Rep. 2012;12(2):213–9. doi:10.1007/s11892-012-0252-0.CrossRefGoogle Scholar
  55. 55.
    Trivedi NJ, Fields J, Mechanick CH, Klein M, Mechanick JI. Lack of correlation between anti-obesity policy and obesity growth rates: review and analysis. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinologist. 2012;1–23. doi:10.4158/EP11379.RA.
  56. 56.
    Sturm R, Powell LM, Chriqui JF, Chaloupka FJ. Soda taxes, soft drink consumption, and children's body mass index. Health Aff. 2010;29(5):1052–8. doi:10.1377/hlthaff.2009.0061.CrossRefGoogle Scholar
  57. 57.
    Biro FM, Wien M. Childhood obesity and adult morbidities. Am J Clin Nutr. 2010;91(5):1499S–505S. doi:10.3945/ajcn.2010.28701B.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Freedman DS, Khan LK, Dietz WH, Srinivasan SR, Berenson GS. Relationship of childhood obesity to coronary heart disease risk factors in adulthood: the Bogalusa Heart Study. Pediatrics. 2001;108(3):712–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T. Do obese children become obese adults? A review of the literature. Prev Med. 1993;22(2):167–77. doi:10.1006/pmed.1993.1014.PubMedCrossRefGoogle Scholar
  60. 60.
    Wang LY, Yang Q, Lowry R, Wechsler H. Economic analysis of a school-based obesity prevention program. Obes Res. 2003;11(11):1313–24. doi:10.1038/oby.2003.178.PubMedCrossRefGoogle Scholar
  61. 61.
    Mechanick JI, Apovian CM. Rethinking our approach to the obese patient: time to create the obesity treatment score. Current opinion in endocrinology, diabetes, and obesity. 2012. doi:10.1097/MED.0b013e328357f15a.
  62. 62.
    Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597–604. doi:10.1056/NEJMoa1105816.PubMedCrossRefGoogle Scholar
  63. 63.
    Doucet E, St-Pierre S, Almeras N, Despres JP, Bouchard C, Tremblay A. Evidence for the existence of adaptive thermogenesis during weight loss. Br J Nutr. 2001;85(6):715–23.PubMedCrossRefGoogle Scholar
  64. 64.
    Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332(10):621–8. doi:10.1056/NEJM199503093321001.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Division of Endocrinology, Diabetes, and Bone DiseaseIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.New YorkUSA

Personalised recommendations