Vol 20. N°2. 2019  |  Abril-Junio de 2019


REVISIÓN - OBESIDAD


TRATAMIENTO FARMACOLÓGICO DE LA OBESIDAD


Autores: GRUPO DE TRABAJO DE OBESIDAD DE LA SOCIEDAD ARGENTINA DE NUTRICIÓN


RESUMEN

La terapia farmacológica es una gran deuda pendiente en el tratamiento de la obesidad. Por este motivo, esta revisión estudia, con criterio médico, los fármacos disponibles en la actualidad para su adecuado abordaje, siempre implementado por un profesional idóneo. Además se exponen cuáles serían las características de un fármaco ideal que pudiera desarrollarse en un futuro, en función del entendimiento complejo de la patología, para ayudar al paciente a transitar la enfermedad crónica, junto con las necesarias herramientas de cambios en el estilo de vida, plan alimentario personalizado, ejercicio, tratamiento cognitivo conductual y, en los casos que lo requieran, cirugía bariátrica.

PALABRAS CLAVE: obesidad; fármacos; tratamiento.

REFERENCIAS:
1. Gadde KM, Apolzan JW, Berthoud HR. Pharmacotherapy for patients with obesity. Clinical Chemistry 2018; 64:1000-000.
2. Hainer V. Overview of new antiobesity drugs. Expert Opin Pharmacother 2014; 15(14):1975-1978.
3. Manning S, Pucci A, Finer N. Pharmacotherapy for obesity: novel agents and paradigms. Ther Adv Chronic Dis 2014; Vol. 5(3) 135-148.
4. Apovian CM, et al. Pharmacological management of obesity: an Endocrine Society Clinical Practice Guideline. J Clin Endo-crinol Metab; 2014.
5. Cappelletti A, Katz M, y col. Obesidad. Encrucijadas y abor-dajes. 2017, pag 400.
6. Bessesen DH, Van-Gaal FL. Obesity 2. Progress and challen-ges in anti-obesity pharmacotherapy. Lancet Diabetes Endo-crinol 2018 Mar; 6(3):237-248.
7. Gadde KM, Apolzan JW, Berthoud HR. Pharmacotherapy for patients with obesity. Clin Chem 2018 Jan; 64(1):118-129
8. Saunders K, Alpala P, Leon I. Pharmacotherapy for obesity. Endocrinol Metab Clin A Am 2016; 45:521-538
9. O'Neil PM, Smith RS, Weissman NJ. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: The BLOOM-DM Study. Obesity journal 2021; Vol 20, 7
10. Khera R, Murad MH, Chandar AK, et al. Association of phar-macological treatments for obesity with weight loss and ad-verse events: a systematic review and meta-analysis. JAMA 2016; 315:2424-34.
11. Benaiges D, Botet JP, Flores-Le Roux JA. Pasado, presente y futuro de la farmacoterapia para la obesidad. Clin Investig Arterioscler 2017.
12. Bohula E. Cardiovascular safety of lorcaserin in overweight or obese patients. New England J oruenal of Medicine 2018; 379:1107-1117 Doi: 10.1056/NEJMoa1808721.
13. Rothman RB, Hendricks EJ. Phentermine cardiovascular safe-ty. Am J Emerg Med 2009 Oct; 27(8):1010-3.
14. Yaman M, Ucok K, Demirbas H, Genc A, Oruc S, Karabacak H, et al. Effects of topiramate use on body composition and resting metabolic rate in migraine patients. Neurol Sci 2013; 34:225-9.
15. Verrotti A, Scaparrotta A, Agostinelli S, di Pillo S, Chiarelli F, Grosso S. Topiramate-induced weight loss: a review. Epilepsy Res 2011; 2011:189-99.
16. Maryanoff BE, Costanzo MJ, Nortey SO, Greco MN, Shank RP, Schupsky JJ, et al. Structure-activity studies on anticon-vulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives. J Med Chem 1998; 41:1315-43.
17. Allison DB, Gadde KM, Garvey WT, et al. Controlled-re-lease phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 2012; 20:330-342.
18. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combina-tion on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-con-trolled, phase 3 trial. Lancet 2011; 377:1341-1352.
19. Fujioka K. Safety and tolerability of medications approved for chronic weight management. Obesity (Silver Spring) 2015; 23 Suppl 1:S7-S11.
20. 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 (SE-QUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012;95:297-308.
21. Aronne LJ, Wadden TA, Peterson C, et al. Evaluation of phentermine and topiramate vs phentermine/topiramate ex-tended-release in obese adults. Obesity (Silver Spring) 2013; 21:2163-2171.
22. EMA. Assessment report, Qsiva, 2013. Disponible en: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR. Pu-blic_assessment_report/human/002350/WC500144300.pdf
23. FDA. https://www.accessdata.fda.gov/Scripts/Cder/Rems/in-dex.cfm
24. Thomas I, Gregg B. Metformin: a review of its history and future: from lilac to longevity. Pediatr Diabetes 2017 Feb;18(1):10-16.
25. Zhou G, Myers R, Li Y, Chen Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin In-vest 2001; 108:1167-1174.
26. Viollet B, Guigas B, Sanz-García N, Leclerc J. Cellular and molecular mechanisms of metformin: an overview. Clinical Science 2012;122:253-270.
27. Misbin RI, Green l, Stadel BV. Lactic acidosis in patients with diabetes treated with etformin. N Engl J Med 2008; 338:265.
28. Mannucci E, Ognibene A, Cremasco F, Bardini G, Mencucci A, et al. Effect of metformin on glucagon-likepeptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 2001; 24: 489-494.
29. Al-qallaf S. Mahmood efficacy and safety of metformin in weight loss. Bahraini Journal of Applied Pharmaceutical Science 2016; 6(06):91-95.
30. Venditti E, Bray GA, Carrion-Petersen ML; the Diabetes Prevention Program Research Group. First versus repeat treatment with a lifestyle intervention program: attendance and weight loss outcomes. Int J Obes 2008; 32:1537-1544.
31. Knowler WC, Fowler SE, Hamman RF; Diabetes Prevention Program Research Group. 10-year follow-up of diabetes in-cidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374:1677-1686.
32. Seifarth C, Schehler B, Schneider HJ. Effectiveness of metfor-min on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes 2013;121:27-31.
33. Glueck CJ, Fontaine RN,Wang P, et al. Metformin reduces weight, centripetal obesity, insulin, leptin,and low densi-ty lipoprotein cholesterol in nondiabetic, morbidly obese with body mass index greather than 30. Metabolism 2001; 50:856-61.
34. Brufani C, Crinò A, Fintini D, Patera PI, Cappa M, Manco M. Systematic review of metformin use in obese nondiabetic chil-dren and adolescents. Horm Res Paediatr 2013; 80(2):78-85.
35. Cappelletti A, Katz M, Gonzáles C. Obesidad, Encrucijadas y abordajes 2017; 397-407.
36. 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 chan-ges for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004 Jan; 27(1):155-61.
37. Dias S, Paredes S, Ribeiro L . Drugs involved in dyslipidemia and obesity treatment: focus on adipose. Tissue Int J Endocrinol 2018 Jan 17; 2018:2637418. Doi: 10.1155/2018/2637418. eCollection 2018.
38. Chao AM, Wadden TA, Berkowitz RI. The safety of pharmaco-logic treatment for pediatric obesity. Expert Opin Drug Saf 2018 Apr; 17(4):379-385. Doi: 10.1080/14740338.2018.
39. Krentz AJ, Fujioka K, Hompesch. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles. Diabe-tes Obes Metab 2016; 18(6):558-70.
40. Greenway FL, Whitehouse MJ, Guttadauria M, et al. Rational design of a combination medication for the treatment of obesi-ty. Obesity (Silver Spring) 2009; 17(1): 30-9. Article that discus-ses the basis for combination bupropion and naltrexone and how they act synergistically.
41. Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O'Neil PM, et al. Weight loss with naltrexone SR/bupropion SR com- bination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 2011; 19:20-110.
42. Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013; 21:43-935.
43. Fujioka K. Safety and tolerability of medications approved for chronic weight management. Obesity (Silver Spring) 2015; 23; S1:S7-11.
44. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of nal-trexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, place-bo-controlled, phase III trial. Lancet 2010; 376(9741):595-605.
45. Nissen SE, Wolski KE, Prcela L, et al. Effect of naltrexone-bupro-pion on major Adverse Cardiovascular Events in Overweight and Obese Patients With cardiovascular risk factors: a randomized clinical trial. JAMA 2016; 315(10):990-1004
46. Halpern B, Faria AM, Halpern A. Bupropion/naltrexone fixed-dose combination for the treatment of obesity. Drugs Today 2011 (Barc) 2011; 47(8):575-81.
47. Iepsen E, Torekov S, Holst J. Therapies for inter-relating diabe-tes and obesity - GLP-1 and obesity. Expert Opin Pharmacother 2014; 15(17):2487-500.
48. Cappelletti A, Katz M, y col. Obesidad. Encrucijadas y aborda-jes, 2017. Ed. Akadia.
49. Secher A, Jelsing J, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight los. J Clin Invest 2014; 124(10):4473-4488.
50. Astrup A, Carraro R, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 ana-log, liraglutide. Int J Obes (Lond) 2012; 36:843-54.
51. Pi-Sunyer X, Astrup A, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. NEJM 2015; 373 (1):11-22.
52. le Roux C, Astrup A, et al. Three years of liraglutide versus placebo for type 2 diabetes risk reduction and weight mana-gement in individuals with prediabetes: a randomised, double-blind trial. Lancet 2017; 389: 1399-409.
53. Pi Sunyer X, et al. AACE 2014. Abstract 700.
54. Davies M, Bergenstal R, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes. The SCALE Diabetes Randomized Clinical Trial. JAMA 2015; 314(7):687-699.
55. Blackman A, Foster G, et al. Effect of liraglutide 3.0 mg in indi-viduals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Inter-national Journal of Obesity 2016; 1-10.
56. Wadden T, Hollander P, et al. Weight maintenance and addi-tional weight loss with liraglutide after low-calorie-diet-induced weight loss: The Scale Maintenance Randomized Study. Int J Obes (Lond) 2013; 37:1443-51.
57. Luppino F, de Wit L, Zitman F, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Archives of General Psychiatry 2010; 67(3):220-229.
58. Zwaan M. Binge eating disorder and obesity. Int J Obes Relat Metab Disord 2001 May; 25 Suppl 1:S51-5.
59. Braquinsky N. Obesidad. Encrucijadas y abordajes. En: Cappe-lletti A, Katz M, y col. Capítulo: Obesidad y Psiquiatría. Vínculos clínicos y farmacológicos. Págs: 409- 416. 2018.
60. Wilson GT, Wilfley DE, Agras WS, Bryson SW. Psychological treatments of binge eating disorder. Arch Gen Psychiatry 2010 Jan; 67(1):94-101.
61. González C. Obesidad. Encrucijadas y Abordajes, Cappelletti A, Katz M. Tratamiento Farmacológico. Un complemento necesa-rio. Pág 397-407, 2017.
62. Scabia G, Barone I, et al. The antidepressant fluoxetine acts on energy balance and leptin sensitivity via BDNF. ScieNtific RE-poRtS 2018; 8:1781.
63. McGuirk J, Silverstone T. The effect of the 5-HT re-uptake inhibi-tor fluoxetine on food intake and body weight in healthy male subjects. Int J Obes 1990; 14:361-72.
64. Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE. Se-rotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 2007; 67:27-55.
65. Huang CC, Chian CY, Lin JD. Short-term treatment of obesity with fluoxetine as a supplement to a low calorie diet. Chan-ggeng Yi Xue Za Zhi 1998 Mar; 21(1):50-6.
66. Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Kim C, Lau J. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2004 Jul 12; 164(13):1395-404.
67. Garay C. Terapia cognitivo conductual y psicofarmacología. Una guía para combinar tratamientos en salud mental 2016; 1º Ed, Buenos Aires: Librería Akadia Editorial.
68. Nielsen JA, Chapin DS, Johnson JL Jr, Torgersen LK. Sertraline, a serotonin-uptake inhibitor, reduces food intake and body weight in lean rats and genetically obese mice. Am J Clin Nutr 1992; 55:185S-9.
69. Wadden TA, Bartlett SJ, Foster GD, Greenstein RA, Wingate BJ, Stunkard AJ, et al. Sertraline and relapse prevention training fo-llowing treatment by very-low-calorie diet: A controlled clinical trial. Obes Res 1995; 3:549-57.
70. Li MF, Cheung BM. Rise and fall of anti-obesity drugs. World J Diabetes 2011; 2:19-23.
71. Roth JD, Trevaskis JL, Turek VF, Parkes DG. Weighing in on syner-gy: preclinical research on neurohumoral anti-obesity combina-tions. Brain Res 201; 1350, 86-94.
72. Aronne LJ, Halseth AE, Burns CM, Miller S, Shen LZ. Enhanced weight loss following coadministration of pramlintide with sibu-tramine or phentermine in a multicenter trial. Obesity 2010; 18, 1739-1746.
73. Day JW, Ottaway N, Patterson JT, Gelfanov V, Smiley D, Gidda J, Findeisen H, Bruemmer D, Drucker DJ, Chaudhary N, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in ro-dents. Nat Chem Biol 2009; 5, 749-757.
74. Woods SC, Lutz TA, Geary N, Langhans W. Pancreatic signals controlling food intake: insulin, glucagon and amylin. Philos Trans R Soc Lond B Biol Sci 2006; 361, 1219-1235.
75. Halford JCG, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol 201; 6, 255-269.
76. Kennett GA, Clifton PG. New approaches to the pharmacolo-gical treatment of obesity: Can they break through the efficacy barrier? Pharmacol Biochem Behav 2010; 97, 63-83.
77. Rodgers RJ, Holch P, Tallett AJ. Behavioural satiety sequence (BSS): Separating wheat from chaff in the behavioural pharma-cology of appetite. Pharmacol Biochem Behav 2010; 97, 3-14.
78. Bhat SP, Sharma A. Current drug targets in obesity pharma-cotherapy: a review. Curr Drug Targets 2017; 18(8):983-993.
79. Srivastava G, Apovian C. Future pharmacotherapy for obesity: new anti-obesity drugs on the horizon. Curr Obes Rep. 2018 Jun;7(2):147-161. Doi: 10.1007/s13679-018-0300-4.




PHARMACOLOGICAL TREATMENT OF OBESITY

SUMMARY

Pharmacological therapy is an outstanding issue in the treatment of obesity. For this reason, this review studies, with medical criterion, the drugs currently available for its proper approach, always carried out by a qualifed professional. In addition it proposes the characteristics of an ideal drug that could be developed in the future, which, according to the deep understanding of the pathology, could help the patient transit the chronic disease, coupled with the necessary tools of lifestyle changes, personalized food plan, exercise routines, cognitive behavioral treatment and in those cases that require it, bariatric surgery.

Key words: obesity; drugs; treatment.



DESCARGAR TEXTO COMPLETO EN PDF