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Current Gastroenterology Reports

Erschienen in:

01.06.2014 | Nutrition and Obesity (S McClave, Section Editor)

New Pharmacological Treatments for the Management of Obesity

verfasst von: Ryan T. Hurt, Jithinraj Edakkanambeth Varayil, Jon O. Ebbert

Erschienen in: Current Gastroenterology Reports | Ausgabe 6/2014

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Abstract

Obesity is quickly becoming the leading preventable cause of death in the USA. Over 60 obesity-related comorbidities exist which increase the complexity and cost of medical care in obese patients. Even a moderate weight loss of 5 % can reduce morbidity associated with these conditions. Lifestyle modification through caloric restriction and enhanced exercise and physical activity remain the first line treatment for obesity. The development of pharmacologic agents for the treatment of obesity has been challenged by both lack of efficacy and serious adverse side effects leading to their removal from market. Two new agents were recently approved by the US Food and Drug Administration to complement lifestyle modification in obese (BMI ≥30 kg/m²) and overweight patients (BMI ≥27 kg/m² and one obesity-related comorbidity). Lorcaserin is a novel serotonin 5-HT_2C selective agonist which has been shown in three phase III studies to significantly reduce weight and cardiovascular risk factors such as diabetes. Phentermine/topiramate extended release (ER) is a novel combination of two agents which have individually been shown to significantly reduce weight. The combination agent phentermine/topiramate ER has been shown to reduce weight in overweight and obese subjects in a number of studies. This article reviews the pharmacology, clinical efficacy, and safety of these new agents compared to past and other presently available medications for the treatment of obesity.

Organization WH. Obesity and overweight: Fact sheet. In: WHO Media centre WHO. 2013. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed February 27, 2014 2014.

2.•

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. The most recent obesity epidemiology data in the United States.PubMedCrossRef

Prevention CfDCa. Morbidity and mortality weekly report. CDC, Atlanta, GA. 2010. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm59e0803a1.htm http://www.cdc.gov/mmwr/pdf/wk/mm59e0803.pdf. Accessed February 27 2014.

Hurt RT, Frazier TH, McClave SA, Kaplan LM. Obesity epidemic: overview, pathophysiology, and the intensive care unit conundrum. JPEN J Parenter Enteral Nutr. 2011;35(5):4S–13S. doi:10.1177/0148607111415110.PubMedCrossRef

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 (Silver Spring). 2008;16(6):1161–77.CrossRef

Beal E. The pros and cons of designating obesity a disease: the new AMA designation stirs debate. Am J Nurs. 2013;113(11):18–9. doi:10.1097/01.NAJ.0000437102.45737.c7.PubMedCrossRef

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–209S.

8.••

Jensen MD, Ryan DH, Apovian CM, Loria CM, Ard JD, Millen BE, et al. AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2013. doi:10.1016/j.jacc.2013.11.004. Recently updated ambulatory obesity management guideline.

Serdula MK, Mokdad AH, Williamson DF, Galuska DA, Mendlein JM, Heath GW. Prevalence of attempting weight loss and strategies for controlling weight. JAMA. 1999;282(14):1353–8.PubMedCrossRef

10.

Hurt RT, Kulisek C, Buchanan LA, McClave SA. The obesity epidemic: challenges, health initiatives, and implications for gastroenterologists. Gastroenterol Hepatol. 2010;6(12):780–92.

11.

Kruger J, Galuska DA, Serdula MK, Jones DA. Attempting to lose weight: specific practices among U.S. adults. Am J Prev Med. 2004;26(5):402–6.PubMedCrossRef

12.

Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360(9):859–73.PubMedCentralPubMedCrossRef

13.

DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med. 2007;356(21):2176–83. doi:10.1056/NEJMct067019.PubMedCrossRef

14.

Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, et al. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014. doi:10.1056/NEJMoa1401329.

15.

Zimmet P, Alberti KG. Surgery or medical therapy for obese patients with type 2 diabetes? N Engl J Med. 2012;366(17):1635–6. doi:10.1056/NEJMe1202443.PubMedCrossRef

16.

Khan LK, Serdula MK, Bowman BA, Williamson DF. Use of prescription weight loss pills among U.S. adults in 1996-1998. Ann Intern Med. 2001;134(4):282–6.PubMedCrossRef

17.

Kaplan LM. Pharmacologic therapies for obesity. Gastroenterol Clin North Am. 2010;39(1):69–79. doi:10.1016/j.gtc.2010.01.001.PubMedCrossRef

18.

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.PubMedCrossRef

19.

Weintraub M. Long-term weight control study: conclusions. Clin Pharmacol Ther. 1992;51(5):642–6.PubMedCrossRef

20.

Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, et al. Valvular heart disease associated with fenfluramine–phentermine. N Engl J Med. 1997;337(9):581–8. doi:10.1056/NEJM199708283370901.PubMedCrossRef

21.

Bray GA. A concise review on the therapeutics of obesity. Nutrition. 2000;16(10):953–60.PubMedCrossRef

22.

Roth BL. Drugs and valvular heart disease. N Engl J Med. 2007;356(1):6–9. doi:10.1056/NEJMp068265.PubMedCrossRef

23.

Mitchell P, Smythe G. Hormonal responses to fenfluramine in depressed and control subjects. J Affect Disord. 1990;19(1):43–51.PubMedCrossRef

24.

FDA USFaDA. FDA announces withdrawal fenfluramine and dexfenfluramine (Fen-Phen). In: withdrawal of fen-phen. FDA. 1997. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm. Accessed February 27 2014.

25.

McNeely W, Goa KL. Sibutramine. A review of its contribution to the management of obesity. Drugs. 1998;56(6):1093–124.PubMedCrossRef

26.

Hainer V, Hainerova IA. Do we need anti-obesity drugs? Diabetes Metab Res Rev. 2012;28 Suppl 2:8–20. doi:10.1002/dmrr.2349.PubMedCrossRef

27.

Lindholm A, Bixo M, Bjorn I, Wolner-Hanssen P, Eliasson M, Larsson A, et al. Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Fertil Steril. 2008;89(5):1221–8. doi:10.1016/j.fertnstert.2007.05.002.PubMedCrossRef

28.

Garcia-Morales LM, Berber A, Macias-Lara CC, Lucio-Ortiz C, Del-Rio-Navarro BE, Dorantes-Alvarez LM. Use of sibutramine in obese Mexican adolescents: a 6-month, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther. 2006;28(5):770–82. doi:10.1016/j.clinthera.2006.05.008.PubMedCrossRef

29.

Sanchez-Reyes L, Fanghanel G, Yamamoto J, Martinez-Rivas L, Campos-Franco E, Berber A. Use of sibutramine in overweight adult Hispanic patients with type 2 diabetes mellitus: a 12-month, randomized, double-blind, placebo-controlled clinical trial. Clin Ther. 2004;26(9):1427–35. doi:10.1016/j.clinthera.2004.09.017.PubMedCrossRef

30.

Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K. A double-blind randomized placebo-controlled trial of sibutramine. Obes Res. 1996;4(3):263–70.PubMedCrossRef

31.

Rossner S. [The trial that killed a drug]. Lakartidningen. 2010;107(39):2339.PubMed

32.

Williams G. Withdrawal of sibutramine in Europe. BMJ. 2010;340:c824. doi:10.1136/bmj.c824.PubMedCrossRef

33.

Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med. 2005;143(5):380–5.PubMedCrossRef

34.

Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther. 2011;18(4):292–9. doi:10.1097/MJT.0b013e3181d070d7.PubMedCrossRef

35.

Bays H. Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. Expert Rev Cardiovasc Ther. 2010;8(12):1777–801. doi:10.1586/erc.10.125.PubMedCrossRef

36.

Bray GA. Drug insight: appetite suppressants. Nat Clin Pract Gastroenterol Hepatol. 2005;2(2):89–95. doi:10.1038/ncpgasthep0092.PubMedCrossRef

37.

Jordan J, Astrup A, Engeli S, Narkiewicz K, Day WW, Finer N. Cardiovascular effects of phentermine and topiramate: a new drug combination for the treatment of obesity. J Hypertens. 2014. doi:10.1097/HJH.0000000000000145.PubMedCentral

38.

Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001;39(1):32–41. doi:10.1002/1098-2396(20010101).PubMedCrossRef

39.

Bays H, Rodbard HW, Schorr AB, Gonzalez-Campoy JM. Adiposopathy: treating pathogenic adipose tissue to reduce cardiovascular disease risk. Curr Treat Options in Cardiovasc Med. 2007;9(4):259–71.CrossRef

40.

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 (Silver Spring). 2011;19(12):2351–60. doi:10.1038/oby.2011.94.CrossRef

41.

Hendricks EJ, Srisurapanont M, Schmidt SL, Haggard M, Souter S, Mitchell CL, et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes (Lond). 2014;38(2):292–8. doi:10.1038/ijo.2013.74ijo201374.CrossRef

42.

Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000;20(3):270–9.PubMedCrossRef

43.

Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281(3):235–42.PubMedCrossRef

44.

Hauptman J, Lucas C, Boldrin MN, Collins H, Segal KR. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000;9(2):160–7.PubMedCrossRef

45.

Miles JM, Leiter L, Hollander P, Wadden T, Anderson JW, Doyle M, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care. 2002;25(7):1123–8.PubMedCrossRef

46.

Sjostrom L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HP, 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(9123):167–72.PubMedCrossRef

47.

Veerman L. Orlistat reduces weight but its cost-effectiveness remains unclear. Evid-Based Nurs. 2013;16(2):56–7. doi:10.1136/eb-2012-100958.PubMedCrossRef

48.

Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007;335(7631):1194–9. doi:10.1136/bmj.39385.413113.25.PubMedCentralPubMedCrossRef

49.

Leblanc ES, O'Connor E, Whitlock EP, Patnode CD, Kapka T. 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(7):434–47.PubMedCrossRef

50.

Weir MA, Beyea MM, Gomes T, Juurlink DN, Mamdani M, Blake PG, et al. Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med. 2011;171(7):703–4. doi:10.1001/archinternmed.2011.103.PubMedCrossRef

51.

Morris M, Lane P, Lee K, Parks D. An integrated analysis of liver safety data from orlistat clinical trials. Obesity Facts. 2012;5(4):485–94. doi:10.1159/000341589.PubMedCrossRef

52.

Orlistat: hepatitis and oxalate nephropathy. Prescrire international. 2012;21(125):71.

53.

Hollander PA, Elbein SC, Hirsch IB, Kelley D, McGill J, Taylor T, 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(8):1288–94.PubMedCrossRef

54.

FDA. FDA approves Belviq to treat some overweight or obese adults. In: FDA NEWS RELEASE. 2012. 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 February 27 2014.

55.

Fleming JW, McClendon KS, Riche DM. New obesity agents: lorcaserin and phentermine/topiramate. Ann Pharmacother. 2013;47(7–8):1007–16. doi:10.1345/aph.1R779.PubMedCrossRef

56.

Katsidoni V, Apazoglou K, Panagis G. Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine. Psychopharmacol. 2011;213(2–3):337–54. doi:10.1007/s00213-010-1887-7.CrossRef

57.

Bubar MJ, Cunningham KA. Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence. Curr Top Med Chem. 2006;6(18):1971–85.PubMedCrossRef

58.

Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, et al. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther. 2008;325(2):577–87. doi:10.1124/jpet.107.133348.PubMedCrossRef

59.

Weissman NJ, Sanchez M, Koch GG, Smith SR, Shanahan WR, Anderson CM. Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials. Circ Cardiovasc Imaging. 2013;6(4):560–7. doi:10.1161/CIRCIMAGING.112.000128.PubMedCrossRef

60.

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.PubMedCrossRef

61.•

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. A large study demonstrating a significant weight loss benefit of lorcaserin.PubMedCrossRef

62.•

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 (Silver Spring). 2012;20(7):1426–36. doi:10.1038/oby.2012.66oby201266. study demonstrating the effect of lorcaserin for weight loss in patients with type 2 diabetes mellitis.CrossRef

63.

U.S Department of Justice DEAOodc. Schedules of controlled substances: placement of lorcaserin into schedule IV. Drug Enforcement Administration, Department of Justice. Springfield. 2012. http://www.deadiversion.usdoj.gov/fed_regs/rules/2012/fr1219.htm. Accessed April, 7 2014.

64.

Cameron F, Whiteside G, McKeage K. Phentermine and topiramate extended release (Qsymia): first global approval. Drugs. 2012;72(15):2033–42. doi:10.2165/11640860-000000000-00000.PubMedCrossRef

65.

Malgarini RB, Pimpinella G. Phentermine plus topiramate in the treatment of obesity. Lancet. 2011;378(9786):125–6. doi:10.1016/S0140-6736(11)61080-5. author reply 6-7.PubMedCrossRef

66.

FDA USFaDA. FDA approves weight-management drug Qsymia. FDA. 2012. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm312468.htm. Accessed February 27 2014.

67.

Bray GA, Hollander P, Klein S, Kushner R, Levy B, Fitchet M, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res. 2003;11(6):722–33. doi:10.1038/oby.2003.102.PubMedCrossRef

68.

Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M. 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 : J Int Assoc Study of Obesity. 2004;28(11):1399–410. doi:10.1038/sj.ijo.0802783.CrossRef

69.

Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41 Suppl 1:S3–9.PubMedCrossRef

70.••

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. The combinations of phentermine and topiramate was found to have significant weight reduction in overweight/ obese subjects.PubMedCrossRef

71.

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.PubMedCentralPubMedCrossRef

72.••

Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, 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(2):297–308. doi:10.3945/ajcn.111.024927. A two year extension to the CONQUER study which did not demonstrate any cardiovascular abnormality in the phentermine/topiramate compared to placebo.PubMedCentralPubMedCrossRef

Titel: New Pharmacological Treatments for the Management of Obesity
verfasst von: Ryan T. Hurt
Jithinraj Edakkanambeth Varayil
Jon O. Ebbert
Publikationsdatum: 01.06.2014
Verlag: Springer US
Erschienen in: Current Gastroenterology Reports / Ausgabe 6/2014
Print ISSN: 1522-8037
Elektronische ISSN: 1534-312X
DOI: https://doi.org/10.1007/s11894-014-0394-0

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