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Obesity in adults: Drug therapy

Author
George A Bray, MD
Section Editor
F Xavier Pi-Sunyer, MD, MPH
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Along with diet, exercise, and behavior modification, drug therapy may be a helpful component of treatment for patients who are overweight or obese. The role of drug therapy has been questioned, however, because of concerns about efficacy, safety, and the observation that body weight slows and then plateaus with continued treatment, and most patients regain weight when their weight-loss drugs are stopped.

The decision to initiate drug therapy in overweight subjects should be made only after a careful evaluation of risks and benefits [1,2]. The first step is evaluation of the patient, which should include determination of the body mass index (BMI), the distribution of fat based upon the waist circumference, and investigations for comorbid conditions such as diabetes mellitus, dyslipidemia, hypertension, heart disease, sleep apnea, and symptomatic osteoarthritis. (See "Obesity in adults: Prevalence, screening, and evaluation".)

Anti-obesity drugs can be useful adjuncts to diet and exercise for adults with obesity and a BMI greater than 30 kg/m2, who have failed to achieve weight loss goals through diet and exercise alone. A trial of drug therapy is also warranted in patients with a BMI of 27 to 29.9 kg/m2 with comorbidities, or in those in whom gastrointestinal bypass surgery is being considered.

This topic will review drug therapy for weight loss in patients with obesity (table 1). Other treatments are discussed separately. (See "Obesity in adults: Overview of management".)

GOALS OF THERAPY

The goal of any treatment, including drug therapy, for overweight subjects must be realistic.

                                                  

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Literature review current through: Nov 2016. | This topic last updated: Fri Mar 25 00:00:00 GMT 2016.
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References
Top
  1. Bray GA, Ryan DH. Medical therapy for the patient with obesity. Circulation 2012; 125:1695.
  2. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 2014; 311:74.
  3. Foster GD, Wadden TA, Vogt RA, Brewer G. What is a reasonable weight loss? Patients' expectations and evaluations of obesity treatment outcomes. J Consult Clin Psychol 1997; 65:79.
  4. Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374:1677.
  5. 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 (Lond) 2005; 29:1153.
  6. Avenell A, Broom J, Brown TJ, et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess 2004; 8:iii.
  7. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27:155.
  8. Leslie WS, Hankey CR, Lean ME. Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review. QJM 2007; 100:395.
  9. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995; 332:621.
  10. Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142:532.
  11. Ara R, Blake L, Gray L, et al. What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review. Health Technol Assess 2012; 16:iii.
  12. Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012; 35:731.
  13. Maggard MA, Shugarman LR, Suttorp M, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med 2005; 142:547.
  14. Lau DC, Obesity Canada Clinical Practice Guidelines Steering Committee and Expert Panel. Synopsis of the 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 2007; 176:1103.
  15. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015; 100:342.
  16. Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy 2000; 20:270.
  17. MacWalter RS, Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharmacother 2003; 37:510.
  18. Sjöström L, Rissanen A, Andersen 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.
  19. 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.
  20. 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.
  21. Rössner S, Sjöström 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.
  22. 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.
  23. Kelley DE, Bray GA, Pi-Sunyer FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial. Diabetes Care 2002; 25:1033.
  24. Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care 2002; 25:1123.
  25. Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care 1998; 21:1288.
  26. Chanoine JP, Hampl S, Jensen C, et al. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005; 293:2873.
  27. Osei-Assibey G, Adi Y, Kyrou I, et al. Pharmacotherapy for overweight/obesity in ethnic minorities and White Caucasians: a systematic review and meta-analysis. Diabetes Obes Metab 2011; 13:385.
  28. Leblanc ES, O'Connor E, Whitlock EP, et al. Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2011; 155:434.
  29. Yancy WS Jr, Westman EC, McDuffie JR, et al. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss. Arch Intern Med 2010; 170:136.
  30. Siebenhofer A, Jeitler K, Horvath K, et al. Long-term effects of weight-reducing drugs in hypertensive patients. Cochrane Database Syst Rev 2013; :CD007654.
  31. Tonstad S, Pometta D, Erkelens DW, et al. The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol 1994; 46:405.
  32. Reitsma JB, Castro Cabezas M, de Bruin TW, Erkelens DW. Relationship between improved postprandial lipemia and low-density lipoprotein metabolism during treatment with tetrahydrolipstatin, a pancreatic lipase inhibitor. Metabolism 1994; 43:293.
  33. Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 2004; :CD004094.
  34. US Food and Drug Administration. FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213038.htm (Accessed on October 20, 2011).
  35. Douglas IJ, Langham J, Bhaskaran K, et al. Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink. BMJ 2013; 346:f1936.
  36. Courtney AE, O'Rourke DM, Maxwell AP. Rapidly progressive renal failure associated with successful pharmacotherapy for obesity. Nephrol Dial Transplant 2007; 22:621.
  37. Singh A, Sarkar SR, Gaber LW, Perazella MA. Acute oxalate nephropathy associated with orlistat, a gastrointestinal lipase inhibitor. Am J Kidney Dis 2007; 49:153.
  38. Weir MA, Beyea MM, Gomes T, et al. Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med 2011; 171:703.
  39. FDA News and Events: FDA approves Belviq to treat some overweight or obese adults. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm309993.htm?utm_campaign=Google2&utm_source=fdaSearch&utm_medium=website&utm_term=lorcaserin&utm_content=4 (Accessed on June 29, 2012).
  40. FDA Highlights of Prescribing Information: BELVIQ (lorcaserin hydrochloride) tablets, for oral use. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022529lbl.pdf (Accessed on September 17, 2012).
  41. Smith SR, Prosser WA, Donahue DJ, et al. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity (Silver Spring) 2009; 17:494.
  42. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363:245.
  43. Fidler MC, Sanchez M, Raether B, 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; 96:3067.
  44. O'Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring) 2012; 20:1426.
  45. Bray GA, Greenway FL. Pharmacological treatment of the overweight patient. Pharmacol Rev 2007; 59:151.
  46. Munro JF, MacCuish AC, Wilson EM, Duncan LJ. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1968; 1:352.
  47. Kim KK, Cho HJ, Kang HC, et al. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people. Yonsei Med J 2006; 47:614.
  48. Kang JG, Park CY, Kang JH, et al. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab 2010; 12:876.
  49. Bray GA. Use and abuse of appetite-suppressant drugs in the treatment of obesity. Ann Intern Med 1993; 119:707.
  50. 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, multicenter trial. Arch Intern Med 2000; 160:2185.
  51. Caterson I, Coutinho W, Finer N, et al. Early response to sibutramine in patients not meeting current label criteria: preliminary analysis of SCOUT lead-in period. Obesity (Silver Spring) 2010; 18:987.
  52. US Food and Drug Administration (FDA). Meridia (sibutramine hydrochloride): Follow-Up to an Early Communication about an Ongoing Safety Review http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm198221.htm (Accessed on October 20, 2011).
  53. European Medicines Agency. European Medicines Agency recommends suspension of marketing authorisation for sibutramine http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2010/01/news_detail_000985.sjsp&jsenabled=true (Accessed on October 20, 2011).
  54. James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010; 363:905.
  55. FDA Drug Safety Communication: FDA Recommends Against the Continued Use of Meridia (sibutramine) http://www.fda.gov/Drugs/DrugSafety/ucm228746.htm#Additional_Information_for_Patients (Accessed on October 13, 2010).
  56. Health Canada. Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia®) from the Canadian Market http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2010/2010_169-eng.php (Accessed on October 13, 2010).
  57. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000; 343:1826.
  58. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003; 289:1537.
  59. McBride BF, Karapanos AK, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004; 291:216.
  60. Bent S, Tiedt TN, Odden MC, Shlipak MG. The relative safety of ephedra compared with other herbal products. Ann Intern Med 2003; 138:468.
  61. 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.
  62. 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.
  63. 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.
  64. 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. Int J Obes Relat Metab Disord 2004; 28:1399.
  65. 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.
  66. Gadde KM, Kopping MF, Wagner HR 2nd, et al. Zonisamide for weight reduction in obese adults: a 1-year randomized controlled trial. Arch Intern Med 2012; 172:1557.
  67. Fontbonne A, Charles MA, Juhan-Vague I, et al. The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group. Diabetes Care 1996; 19:920.
  68. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393.
  69. Singh-Franco D, Perez A, Harrington C. The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2011; 13:169.
  70. Ratner RE, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med 2004; 21:1204.
  71. Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 2008; 31:1816.
  72. Aronne LJ, Halseth AE, Burns CM, et al. Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial. Obesity (Silver Spring) 2010; 18:1739.
  73. Hollander PA, Levy P, Fineman MS, et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 2003; 26:784.
  74. Aronne L, Fujioka K, Aroda V, et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 2007; 92:2977.
  75. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm (Accessed on January 05, 2015).
  76. Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009; 374:1606.
  77. Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015; 373:11.
  78. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. In J Obes (Lond) 2013; 37:1443.
  79. Bosch B, Venter I, Stewart RI, Bertram SR. Human chorionic gonadotrophin and weight loss. A double-blind, placebo-controlled trial. S Afr Med J 1990; 77:185.
  80. Lijesen GK, Theeuwen I, Assendelft WJ, Van Der Wal G. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. Br J Clin Pharmacol 1995; 40:237.
  81. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022580s000lbl.pdf (Accessed on July 18, 2012).
  82. Gadde KM, Allison DB, Ryan DH, 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; 377:1341.
  83. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012; 95:297.
  84. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 2012; 20:330.
  85. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM312598.pdf (Accessed on July 18, 2012).
  86. 2 new drugs for weight loss. Med Lett Drugs Ther 2012; 54:69.
  87. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm413896.htm.
  88. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376:595.
  89. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 2013; 21:935.
  90. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 2011; 19:110.
  91. Caixàs A, Albert L, Capel I, Rigla M. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. Drug Des Devel Ther 2014; 8:1419.
  92. Greenway FL, Dunayevich E, Tollefson G, et al. Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo. J Clin Endocrinol Metab 2009; 94:4898.
  93. Sharfstein JM, Psaty BM. Evaluation of the Cardiovascular Risk of Naltrexone-Bupropion: A Study Interrupted. JAMA 2016; 315:984.
  94. Nissen SE, Wolski KE, Prcela L, et al. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA 2016; 315:990.
  95. Pittler MH, Ernst E. Guar gum for body weight reduction: meta-analysis of randomized trials. Am J Med 2001; 110:724.
  96. Saper RB, Eisenberg DM, Phillips RS. Common dietary supplements for weight loss. Am Fam Physician 2004; 70:1731.
  97. Mhurchu CN, Poppitt SD, McGill AT, et al. The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults. Int J Obes Relat Metab Disord 2004; 28:1149.
  98. Onakpoya I, Hung SK, Perry R, et al. The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials. J Obes 2011; 2011:509038.
  99. Jurgens TM, Whelan AM, Killian L, et al. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane Database Syst Rev 2012; 12:CD008650.
  100. Tian H, Guo X, Wang X, et al. Chromium picolinate supplementation for overweight or obese adults. Cochrane Database Syst Rev 2013; :CD010063.
  101. Rader JI, Delmonte P, Trucksess MW. Recent studies on selected botanical dietary supplement ingredients. Anal Bioanal Chem 2007; 389:27.
  102. Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005; 118:998.
  103. Cohen PA, McCormick D, Casey C, et al. Imported compounded diet pill use among Brazilian women immigrants in the United States. J Immigr Minor Health 2009; 11:229.
  104. US Food and Drug Administration (FDA). FDA Warns Consumers about Brazilian Diet Pills Found to Contain Active Drug Ingredients, January 2006. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108578.htm (Accessed on October 20, 2011).
  105. Davies KM, Heaney RP, Recker RR, et al. Calcium intake and body weight. J Clin Endocrinol Metab 2000; 85:4635.
  106. Shapses SA, Heshka S, Heymsfield SB. Effect of calcium supplementation on weight and fat loss in women. J Clin Endocrinol Metab 2004; 89:632.
  107. Reid IR, Horne A, Mason B, et al. Effects of calcium supplementation on body weight and blood pressure in normal older women: a randomized controlled trial. J Clin Endocrinol Metab 2005; 90:3824.
  108. Yanovski JA, Parikh SJ, Yanoff LB, et al. Effects of calcium supplementation on body weight and adiposity in overweight and obese adults: a randomized trial. Ann Intern Med 2009; 150:821.
  109. Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110:1093.
  110. Licinio J, Caglayan S, Ozata M, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A 2004; 101:4531.
  111. Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282:1568.
  112. Rosenbaum M, Goldsmith R, Bloomfield D, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005; 115:3579.
  113. 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.
  114. Gantz I, Erondu N, Mallick M, et al. Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults. J Clin Endocrinol Metab 2007; 92:1754.
  115. Wynne K, Park AJ, Small CJ, et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes 2005; 54:2390.
  116. Fehm HL, Smolnik R, Kern W, et al. The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans. J Clin Endocrinol Metab 2001; 86:1144.
  117. Hallschmid M, Smolnik R, McGregor G, et al. Overweight humans are resistant to the weight-reducing effects of melanocortin4-10. J Clin Endocrinol Metab 2006; 91:522.