Pharmacotherapy for Obesity

  • Giuseppe DerosaEmail author
  • Pamela Maffioli
Part of the Nutrition and Health book series (NH)


The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake; when the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In the past years, a number of medications have been approved for the treatment of obesity, but many of them have been withdrawn from the market because of their adverse effects. Actually only orlistat is available for use in Europe, because amphetamines, rimonabant, and sibutramine licenses have been withdrawn due to lack of efficacy leading to an unfavorable benefit/risk ratio linked to amphetamines; psychiatric disorders, especially depression, linked to rimonabant; and an increased risk of nonfatal myocardial infarction or stroke linked to sibutramine.

Recently FDA approved two new drugs for the treatment of obesity: the first one was lorcaserin and the second one was phentermine/topiramate extended-release combination. Both these newly approved drugs seem promising and safe also in type 2 diabetic patients; however, long-term studies are ongoing to evaluate their cardiovascular safety.


Amphetamines Exenatide Lorcaserin Obesity Orlistat Phentermine and topiramate extended-release 



The authors certify that they have no affiliation with, or financial involvement in, any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript.


  1. 1.
    National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults–the Evidence Report. Obes Res. 1998;6(2):51S–209.Google Scholar
  2. 2.
    Fried M, Hainer V, Basdevant A, Buchwald H, Dietel M, Finer N, Greve JW, Horber F, Mathus-Vliegen E, Scopinaro N, Steffen R, Tsigos C, Weiner R, Widhalm K. Interdisciplinary European guidelines on surgery for severe obesity. Rozhl Chir. 2008;87:468–76.PubMedGoogle Scholar
  3. 3.
    Pagotto U, Vanuzzo D, Vicennati V, Pasquali RG. Pharmacological therapy of obesity. G Ital Cardiol (Rome). 2008;9:83S–93.Google Scholar
  4. 4.
    Marović D. Elevated body mass index fatty liver. Srp Arh Celok Lek. 2008;136:122–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Lavie CJ, Artham SM, Milani RV, Ventura HO. The obesity paradox: impact of obesity on the prevalence prognosis of cardiovascular diseases. Postgrad Med. 2008;120:34–41.CrossRefPubMedGoogle Scholar
  6. 6.
    Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    American Diabetes Association. Nutrition principles and recommendations in diabetes. Diabetes Care. 2004;27(S1):36–46.Google Scholar
  8. 8.
    American Diabetes Association. Physical activity/exercise and diabetes. Diabetes Care. 2004;27(S1):58–62.Google Scholar
  9. 9.
    Lee M, Aronne LJ. Weight management for type 2 diabetes mellitus: global cardiovascular risk reduction. Am J Cardiol. 2007;99:68B–79.CrossRefPubMedGoogle Scholar
  10. 10.
    WIN-Publication. Prescription medications for the treatment of obesity. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Retrieved 14 Jan 2009.
  11. 11.
    Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet. 2007;369:71–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Soyka M. Rimonabant and depression. Pharmacopsychiatry. 2008;41:204–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med. 2004;164:994–1003.CrossRefPubMedGoogle Scholar
  14. 14.
    European Medicines Agency recommends suspension of marketing authorisation for sibutramine- Last accessed 15 Sept 2010.
  15. 15.
  16. 16.
    James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA. Renz CL; the SCOUT Investigators. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects N Engl J Med. 2010;363:905–17.Google Scholar
  17. 17.
    Colombo G, Agabio R, Diaz G, Lobina C, Reali R, Gessa GL. Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci. 1998;63:113–7.CrossRefGoogle Scholar
  18. 18.
  19. 19.
    Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med. 2005;143(5):380–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Bays HE, Rodbard RW, Schorr AB, González-Campoy JM. Adiposopathy: treating pathogenic adipose tissue to reduce cardiovascular disease risk. Curr Treat Options Cardiovasc Med. 2007;9(4):259–71.CrossRefPubMedGoogle Scholar
  21. 21.
    Pasquali R, Casimirri F, Melchionda N, Grossi G, Bortoluzzi L, Morselli Labate AM, Stefanini C, Raitano A. Effects of chronic administration of ephedrine during very-low-calorie diets on energy expenditure, protein metabolism and hormone levels in obese subjects. Clin Sci (Lond). 1992;82(1):85–92.Google Scholar
  22. 22.
    Lorello C, Goldfield GS, Doucet E. Methylphenidate hydrochloride increases energy expenditure in healthy adults. Obesity (Silver Spring). 2008;16(2):470–2.CrossRefGoogle Scholar
  23. 23.
    Coyne TC. Phentermine—resin or salt—there are differences. Arch Intern Med. 1997;157(20):2381–2.CrossRefPubMedGoogle Scholar
  24. 24.
    Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab. 2010;12(10):876–82.CrossRefPubMedGoogle Scholar
  25. 25.
    Kim KK, Cho HJ, Kang HC, Youn BB, Lee KR. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people. Yonsei Med J. 2006;47(5):614–25.CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Weintraub M, Hasday JD, Mushlin AI, Lockwood DH. A double-blind clinical trial in weight control use of fenfluramine and phentermine alone and in combination. Arch Intern Med. 1984;144(6):1143–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Vallé-Jones JC, Brodie NH, O’Hara H, O’Hara J, McGhie RL. A comparative study of phentermine and diethylpropion in the treatment of obese patients in general practice. Pharmatherapeutica. 1983;3(5):300–4.PubMedGoogle Scholar
  28. 28.
    Weintraub M, Sundaresan PR, Madan M, Schuster B, Balder A, Lasagna L, Cox C. Long-term weight control study I (weeks 0 to 34) The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther. 1992;51:586–94.CrossRefPubMedGoogle Scholar
  29. 29.
    Leung WY, Thomas GN, Chan JC, Tomlinson B. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther. 2003;25(1):58–80.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhi J, Moore R, Kanitra L, Mulligan TE. Pharmacokinetic evaluation of the possible interaction between selected concomitant medications and orlistat at steady state in healthy subjects. J Clin Pharmacol. 2002;42:1011–9.CrossRefPubMedGoogle Scholar
  31. 31.
    MacWalter RS, Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharmacother. 2003;37:510–2.CrossRefPubMedGoogle Scholar
  32. 32.
    Wong NN, Cheng-Lai A. Orlistat. Heart Dis. 2000;2:174–81.PubMedGoogle Scholar
  33. 33.
  34. 34.
    Derosa G, Cicero AF, Murdolo G, Ciccarelli L, Fogari R. Comparison of metabolic effects of orlistat and sibutramine treatment in type 2 diabetic obese patients. Diabetes Nutr Metab. 2004;17(4):222–9.PubMedGoogle Scholar
  35. 35.
    Derosa G, Cicero AF, Murdolo G, Piccinni MN, Fogari E, Bertone G, Ciccarelli L, Fogari R. Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients. Diabetes Obes Metab. 2005;7(1):47–55.CrossRefPubMedGoogle Scholar
  36. 36.
    Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Gravina A, Mereu R, D’Angelo A, Fogari E, Palumbo I, Randazzo S, Cicero AF. Comparison of orlistat treatment and placebo in obese type 2 diabetic patients. Expert Opin Pharmacother. 2010;11(12):1971–82.CrossRefPubMedGoogle Scholar
  37. 37.
    Derosa G, Cicero AF, D’Angelo A, Fogari E, Maffioli P. Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes. J Clin Pharm Ther. 2012;37(2):187–95.CrossRefPubMedGoogle Scholar
  38. 38.
    Derosa G, Maffioli P, Ferrari I, D’Angelo A, Fogari E, Palumbo I, Randazzo S, Cicero AF. Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Endocr J. 2010;57(9):777–86.CrossRefPubMedGoogle Scholar
  39. 39.
    Derosa G, Maffioli P, Ferrari I, D’Angelo A, Fogari E, Palumbo I, Randazzo S, Cicero AF. Comparison between orlistat plus L-carnitine and orlistat alone on inflammation parameters in obese diabetic patients. Fundam Clin Pharmacol. 2011;25(5):642–51.CrossRefPubMedGoogle Scholar
  40. 40.
    Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, Barnett AH, Kumar S. Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines. Metabolism. 2004;53:430–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Kelley DE, Bray GA, Pi-Sunyer FX, Klein S, Hill J, Miles J, Hollander P. 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(6):1033–41.CrossRefPubMedGoogle Scholar
  42. 42.
    Jacob S, Rabbia M, Meier MK, Hauptman J. Orlistat 120 mg improves glycaemic control in type 2 diabetic patients with or without concurrent weight loss. Diabetes Obes Metab. 2009;11(4):361–71.CrossRefPubMedGoogle Scholar
  43. 43.
    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. A 1-year randomized double-blind study. Diabetes Care. 1998;21:1288–94.CrossRefPubMedGoogle Scholar
  44. 44.
  45. 45.
    Lam DD, Przydzial MJ, Ridley SH, Yeo GS, Rochford JJ, O’Rahilly S, Heisler LK. Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology. 2008;149(3):1323–8.CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Weissman NJ, Tighe Jr JF, Gottdiener JS, Gwynne JT. An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. Sustained-Release Dexfenfluramine Study Group N Engl J Med. 1998;339(11):725–32.Google Scholar
  47. 47.
    Smith SR, Weissman NJ, Anderson CM. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245–56. CrossRefPubMedGoogle Scholar
  48. 48.
    O’Neil PM, Smith SR, Weissman NJ, Fidler MC, Sanchez M, Zhang J, Raether B, Anderson CM, Shanahan WR. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring). 2012;20(7):1426–36.CrossRefGoogle Scholar
  49. 49.
  50. 50.
    Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T, Tam PY, Troupin B, Day WW. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20(2):330–42.CrossRefGoogle Scholar
  51. 51.
    Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, Day WW. 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.CrossRefPubMedGoogle Scholar
  52. 52.
    Winslow DH, Bowden CH, Didonato KP, McCullough PA. A randomized, double-blind, placebo-controlled study of an oral, extended-release formulation of phentermine/topiramate for the treatment of obstructive sleep apnea in obese adults. Sleep. 2012;35(11):1529–39.PubMedCentralPubMedGoogle Scholar
  53. 53.
    Weir GC, Leahy JL. Pathogenesis of non-insulin-dependent (type II) diabetes mellitus. In: Kahn CR, Weir GE, editors. Joslin’s diabetes mellitus. 13th ed. Phildelphia: Lea & Febiger; 1994. p. 240–64.Google Scholar
  54. 54.
    Bogardus C. Metabolic abnormalities in the development of non-insulin-dependent diabetes mellitus. In: LeRoith D, Taylor SI, Olefski JM, editors. Diabetes mellitus. Philadelphia: Lippincott-Raven; 1996. p. 459.Google Scholar
  55. 55.
    DeFronzo RA. Lilly Lecture 1987. The triumvirate: B-cell, muscle, liver. A collision responsible for NIDDM. Diabetes. 1988;37:667–87.CrossRefPubMedGoogle Scholar
  56. 56.
    Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–39.CrossRefPubMedGoogle Scholar
  57. 57.
    Derosa G, Maffioli P. Glp-1 agonists Exenatide and Liraglutide: a review about their safety and efficacy. Curr Clin Pharmacol. 2012;7(3):214–28.CrossRefPubMedGoogle Scholar
  58. 58.
    Derosa G, Franzetti IG, Querci F, et al. Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes. Diabet Med. 2012;29(12):1515–23.CrossRefPubMedGoogle Scholar
  59. 59.
    Derosa G, Putignano P, Bossi AC, Bonaventura A, Querci F, Franzetti IG, Guazzini B, Testori G, Fogari E, Maffioli P. Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients. Eur J Pharmacol. 2011;666(1–3):251–6.CrossRefPubMedGoogle Scholar
  60. 60.
    Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Ragonesi PD, Querci F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, D’Angelo A, Cicero AF. Exenatide versus glibenclamide in patients with diabetes. Diabetes Technol Ther. 2010;12(3):233–40.CrossRefPubMedGoogle Scholar
  61. 61.
    Young AA. Glucagon-like peptide-1, exendin and insulin sensitivity. In: Hansen B, Shafrir E, editors. Insulin resistance and insulin resistance syndrome. Chap 14. New York: Taylor & Francis; 2002. p. 235–62.CrossRefGoogle Scholar
  62. 62.
    Knudsen LB, Nielsen PF, Huusfeldt PO, Johansen NL, Madsen K, Pedersen FZ, Thøgersen H, Wilken M, Agersø H. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem. 2000;43(9):1664–9.CrossRefPubMedGoogle Scholar
  63. 63.
    Knudsen LB. Glucagon-like peptide-1: the basis of a new class of treatment for type 2 diabetes. J Med Chem. 2004;47:4128–34.CrossRefPubMedGoogle Scholar
  64. 64.
    Parkes D, Jodka C, Smith P, Nayak S, Rinehart L, Gingerich R, Chen K, Young A. Pharmacokinetic actions of exenatide-4 in the rat: comparison with glucagon-like peptide-1. Drug Dev Res. 2001;53:260–7.CrossRefGoogle Scholar
  65. 65.
    Copley K, McCowen K, Hiles R, Nielsen LL, Young A, Parkes DG. Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab. 2006;7:367–74.CrossRefPubMedGoogle Scholar
  66. 66.
    Simonsen L, Holst JJ, Deacon CF. Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular filtration in anaesthetised pigs. Diabetologia. 2006;49:706–12.CrossRefPubMedGoogle Scholar
  67. 67.
    Linnebjerg H, Kothare PA, Park S, Mace K, Reddy S, Mitchell M, Lins R. Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol. 2007;64:317–27.CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, Taylor K. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007;30:1487–93.CrossRefPubMedGoogle Scholar
  69. 69.
    Malone J, Trautmann M, Wilhelm K, Taylor K, Kendall DM. Exenatide once weekly for the treatment of type 2 diabetes. Expert Opin Investig Drugs. 2009;18:359–67.CrossRefPubMedGoogle Scholar
  70. 70.
    Tracy MA, Ward KL, Firouzabadian L, Wang Y, Dong N, Qian R, Zhang Y. Factors affecting the degradation rate of poly(lactide-co-glycolide) microspheres in vivo and in vitro. Biomaterials. 1999;20:1057–62.CrossRefPubMedGoogle Scholar
  71. 71.
    Malm-Erjefält M, Bjørnsdottir I, Vanggaard J, Helleberg H, Larsen U, Oosterhuis B, van Lier JJ, Zdravkovic M, Olsen AK. Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010;38(11):1944–53.CrossRefPubMedGoogle Scholar
  72. 72.
    Agersø H, Jensen LB, Elbrønd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002;45(2):195–202.CrossRefPubMedGoogle Scholar
  73. 73.
    Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.CrossRefPubMedCentralPubMedGoogle Scholar
  74. 74.
    Larsen MH, Rosenbrock H, Sams-Dodd F, Mikkelsen JD. Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine. Eur J Pharmacol. 2007;555(2–3):115–21.CrossRefPubMedGoogle Scholar
  75. 75.
    Astrup A, Meier DH, Mikkelsen BO, Villumsen JS, Larsen TM. Weight loss produced by tesofensine in patients with Parkinson’s or Alzheimer’s disease. Obesity (Silver Spring). 2008;16(6):1363–9.CrossRefGoogle Scholar
  76. 76.
    Gadde KM, Yonish GM, Foust MS, Wagner HR. Combination therapy of zonisamide and bupropion for weight reduction in obese women: a preliminary, randomized, open-label study. J Clin Psychiatry. 2007;68(8):1226–9.CrossRefPubMedGoogle Scholar
  77. 77.
    Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–60.CrossRefPubMedGoogle Scholar
  78. 78.
    Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. Clin Endocrinol Metab. 2001;86(12):5992.CrossRefGoogle Scholar
  79. 79.
    Beck B, Richy S, Stricker-Krongrad A. Feeding response to ghrelin agonist and antagonist in lean and obese Zucker rats. Life Sci. 2004;76(4):473–8.CrossRefPubMedGoogle Scholar
  80. 80.
    Druce MR, Bloom SR. Oxyntomodulin: a novel potential treatment for obesity. Treat Endocrinol. 2006;5(5):265–72.CrossRefPubMedGoogle Scholar
  81. 81.
    Katsuura G, Asakawa A, Inui A. Roles of pancreatic polypeptide in regulation of food intake. Peptides. 2002;23(2):323–9.CrossRefPubMedGoogle Scholar
  82. 82.
    Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab. 2003;88(8):3989–92.CrossRefPubMedGoogle Scholar
  83. 83.
    Lutz TA. Control of energy homeostasis by amylin. Cell Mol Life Sci. 2012;69:1947–65.CrossRefPubMedGoogle Scholar
  84. 84.
    Lutz TA. Control of food intake and energy expenditure by amylin-therapeutic implications. Int J Obes (Lond). 2009;33(1):S24–7.CrossRefGoogle Scholar
  85. 85.
    Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG, Weyer C. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes Res. 2004;12(4):661–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Internal Medicine and TherapeuticsUniversity of PaviaPaviaItaly

Personalised recommendations