Modern drugs for obesity and metabolic syndrome treatment (Review)
Abstract
The article reviews modern anti-obesity drugs to identify new trends in effective and safe risk factors reduction (diabetes, cardiovascular and musculoskeletal diseases, cancer). Some anti-obesity drugs have a high risk of adverse effects on the CNS and cardiovascular system, so they should be used for a short-term therapy only. These drugs are cannabinoid receptor antagonists (Rimonabant), neuronal NE and 5-HT reuptake inhibitors (Sibutramine), neuronal NE, 5-HT, DA reuptake inhibitor (Tesofensine), 5HT2с receptors agonist (Lorcaserin) and other drugs affecting the central and peripheral mediator systems. That is why the treatment of obesity should focus on safe drugs that affected fat absorption (Orlistat), activated energy metabolism (Adipokines), methionine aminopeptidase 2 (MetAP2) inhibitors (Beloranib) etc. The combination of anti-obesity drugs with various mechanisms of action increases the effectiveness and reduces adverse effects (Contrave®, Empatic™, Qsymia etс).
About the Authors
M. L. Maximov
I.M. Sechenov First MSMU
Russian Federation
Russian Federation
Maxim L. Maximov, Professor, the Department of clinical pharmacology and internal diseases propedeutics
13, Nikitsky Boulevard, Moscow, 121019
O. V. Dralova
I.M. Sechenov First MSMU
Russian Federation
Russian Federation
Assistant professor, the Department of clinical pharmacology and internal diseases propedeutics
Moscow
V. G. Kukes
I.M. Sechenov First MSMU
Russian Federation
Russian Federation
Member of RAS, Head of the Department of clinical pharmacology and internal diseases propedeutics
Moscow
V. N. Chubarev
I.M. Sechenov First MSMU
Russian Federation
Russian Federation
Professor, the Department of clinical pharmacology and internal diseases propedeutics
Moscow
V. V. Tarasov
I.M. Sechenov First MSMU
Russian Federation
Russian Federation
Head of the innovative activity department, head of the Department of pharmacology, the Faculty of Pharmacology
Moscow
References
1. Finucane M., Stevens G., Cowan M., Danaei G., Lin J., Paciorek C., Singh G., Gutierrez H., Lu Y., Bahalim A., Farzadfar F., Riley L., Ezzati M. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. The Lancet. 2011; 377(9765); 557–567. DOI: 10.1016/S0140-6736(10)62037-5.
2. Wilson J.D., Foster D.W., Kronenberg H.M., Larsen P.R. (eds). Williams Textbook of Edocrinology. 9th ed. Philadelphia: Saunders; 1998.
3. Isomaa B., Almgren P., Tuomi T., Forsen B., Lahti K., Nissen M., Taskinen M., Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001; 24(4): 683–689. DOI: 10.2337/diacare.24.4.683.
4. OECD Obesity [home page on the Internet]. Update OECD Health Statistics. June 2014. Available at: http://www.oecd.org/health/Obesity-Update-2014.pdf (accessed September 7, 2015).
5. Obesity: guidance on the prevention, identification, assessment and management of overweight and obesity in adults and children : quick reference guide 1: for local authorities, schools and early years providers, workplaces and the public [home page on the Internet]. National Institute for Health and Clinical Excellence. December 2006. Available at: https://www.croydon.gov.uk/sites/default/files/articles/downloads/nicela.PDF (accessed September 7, 2015).
6. Snow V. Pharmacologic and Surgical Management of Obesity in Primary Care: A Clinical Practice Guideline from the American College of Physicians. Annals of Internal Medicine. 2005. 142(7): 525.DOI:10.7326/0003-4819-142-7-200504050-00011.
7. Boelsen-Robinson T., Peeters A., Beauchamp A., Chung A., Gearon E., Backholer K. A systematic review of the effectiveness of whole-of-community interventions by socioeconomic position. Obes. Rev. 2015; 16(9): 806–816. DOI: 10.1111/obr.12297.
8. 10 facts on obesity [home page on the Internet]. WHO. 2014. May. Available at: http://www.who.int/features/factfiles/obesity/ru/ (accessed September 7, 2015).
9. Lau D., Douketis J., Morrison K., Hramiak I., Sharma A., Ur E. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. Canadian Medical Association J. 2007; 176(8): S1–S13. DOI: 10.1503/cmaj.061409.
10. Global Health Risks: mortality and burden of disease attributable to selected major risks 2009 [home page on the Internet]. WHO. November 12, 2011. Available at: http://www.who.int/healthinfo/global_burden_disease/global_health_risks/en/index.html (accessed September 7, 2015).
11. Obesity and overweight Fact sheet № 311 [home page on the Internet]. WHO [cited November 15, 2011]. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/index.html (accessed September 7, 2015).
12. Jensen M., Ryan D., Apovian C., Ard J., Comuzzie A., Donato K., Hu F., Hubbard V., Jakicic J., Kushner R., Loria C., Millen B., Nonas C., Pi-Sunyer F., Stevens J., Stevens V., Wadden T., Wolfe B., Yanovski S. 2013 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. Circulation. 2013; 129(25_suppl_2): S102–S138. Available at: http://dx.doi.org/10.1161/01.cir.0000437739.71477.ee (accessed September 7, 2015).
13. Rydén L., Grant P.J., Anker S.D. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur. Heart J. 34(39): 3035–3087. DOI: 10.1093/eurheartj/eht108. Epub 2013 Aug 30.
14. Mancia G., Bombelli M., Corrao G. et al. Metabolic Syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) Study: Daily Life Blood Pressure, Cardiac Damage, and Prognosis. Hypertension. 2006; 49(1): 40–47. DOI: 10.1161/01.hyp.0000251933.22091.24.
15. Lakka H. The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men. JAMA. 2002; 288(21): 2709. DOI:10.1001/jama.288.21.2709.
16. Garrison R., Kannel W., Stokes J., Castelli W. Incidence and precursors of hypertension in young adults: The Framingham offspring study. Preventive Medicine. 1987; 16(2): 235–251. DOI: 10.1016/0091-7435(87)90087-9.
17. American Medical Association. Policy H-440.842. Recognition of Obesity as a Disease; 2013.
18. McFarlane S., Banerji M., Sowers J. Insulin Resistance and Cardiovascular Disease 1. The J. of Clinical Endocrinology & Metabolism. 2001; 86(2): 713–718. DOI: 10.1210/jcem.86.2.7202.
19. Rahmouni K., Correia M., Haynes W., Mark A. Obesity-Associated Hypertension: New Insights Into Mechanisms. Hypertension. 2004; 45(1): 9–14. DOI: 10.1161/01.hyp.0000151325.83008.b4.
20. Mule G., Nardi E., Cottone S. et al. Influence of metabolic syndrome on hypertension-related target organ damage. J. Intern. Med. 2005; 257(6): 503–513. DOI: 10.1111/j.1365-2796.2005.01493.x.
21. Schillaci G., Pirro M., Vaudo G. et al. Metabolic syndrome is associated with aortic stiffness in untreated essential hypertension. Hypertension. 2005; 45(6): 1078–1082. DOI: 10.1161/01.hyp.0000165313.84007.7d.
22. Cuspidi C., Meani S., Fusi V. et al. Prevalence and correlates of left atrial enlargement in essential hypertension: role of ventricular geometry and the metabolic syndrome. J. of Hypertension. 2005; 23(4): 875-882. DOI: 10.1097/01.hjh.0000163158.14493.23.
23. Kawamoto R., Tomita H., Oka Y., Kodama A., Kamitani A. Metabolic Syndrome Amplifies the LDL-Cholesterol Associated Increases in Carotid Atherosclerosis. Intern Med. 2005; 44(12): 1232–1238. DOI: 10.2169/internalmedicine.44.1232.
24. Cuspidi C., Meani S., Valerio C. et al. Ambulatory blood pressure, target organ damage and left atrial size in never-treated essential hypertensive individuals. J. of Hypertension. 2005; 23(8): 1589–1595. DOI: 10.1097/01.hjh.0000174608.26404.84.
25. Prevention of cardiovascular disease – Guidance on the prevention of cardiovascular disease at the population level. NICE Public Health Guideline. June 2010. Available at: https://www.nice.org.uk/guidance/ph25 (accessed September 7, 2015).
26. Bray G. Treatment and secondary prevention of obesity. Nutrition. 2000; 16(5): 384–385. DOI: 10.1016/s0899-9007(00)00263-x.
27. National Heart, Lung, and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Obes. Res. 1998; 6(suppl): 51– 210.
28. Eckel R., Grundy S., Zimmet P. The metabolic syndrome. The Lancet. 2005; 365(9468): 1415–1428. DOI: 10.1016/s0140-6736(05)66378-7.
29. Snow V., Barry P., Fitterman N., Qaseem A., Weiss K. Pharmacologic and Surgical Management of Obesity in Primary Care: A Clinical Practice Guideline From the American College of Physicians. ACC Current Journal Review. 2005; 14(7): 11. DOI: 10.1016/j.accreview.2005.06.023.
30. Dalton S. et al. (eds). Overweight and weight management The health professional’s guide to understanding and practice. MD: Aspen Publishers; 1997.
31. Laaksonen D., Lindstrom J., Lakka T. et al. Physical Activity in the Prevention of Type 2 Diabetes: The Finnish Diabetes Prevention Study. Diabetes. 2004; 54(1): 158–165. DOI: 10.2337/diabetes.54.1.158.
32. National Heart, Lung, and Blood Institute and North American Association for the Study of Obesity. Practical Guide on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: National Institutes of Health; October 2000. NIH publication № 00-4084.
33. Bray G., Ryan D. Medical Therapy for the Patient With Obesity. Circulation. 2012; 125(13): 1695–1703. DOI: 10.1161/circulationaha.111.026567.
34. Rayner J., Neubauer S., Rider O. The paradox of obesity cardiomyopathy and the potential for weight loss as a therapy. Obes. Rev. 2015; 16(8): 679–690. DOI: 10.1111/obr.12292.
35. Medicinal products used in weight control [home page in the Internet]. Rescrire [cited December 2012]. Available at: http://english.prescrire.org/Docu/DOCSEUROPE/20121231_En_Prescrire_AnswerEMAConsultGuidelineWeightControl.pdf (accessed September 7, 2015).
36. Hainer V., Toplak H., Mitrakou A. Treatment Modalities of Obesity: What fits whom? Diabetes Care. 2008; 31(Supplement 2): S269–S277. DOI: 10.2337/dc08-s265.
37. Padwal R., Majumdar S. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. The Lancet. 2007; 369(9555): 71–77. DOI: 10.1016/s0140-6736(07)60033-6.
38. Grundy S. Clinical Management of Metabolic Syndrome: Report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association Conference on Scientific Issues Related to Management. Circulation. 2004; 109(4): 551–556. DOI: 10.1161/01.cir.0000112379.88385.67.
39. Atkinson R., Blank R., Loper J., Schumacher D., Lutes R. Combined Drug Treatment of Obesity. Obesity Research. 1995; 3(S4): 497S–500S. DOI: 10.1002/j.1550-8528.1995.tb00218.x.
40. Matias I., Di Marzo V. Endocannabinoids and the control of energy balance. Trends in Endocrinology & Metabolism. 2007; 18(1): 27–37. DOI: 10.1016/j.tem.2006.11.006.
41. Maldonado R. Study of cannabinoid dependence in animals. Pharmacology & Therapeutics. 2002; 95(2): 153– 164. DOI: 10.1016/s0163-7258(02)00254-1.
42. Questions and answers on the suspension of medicines containing sibutramine Outcome of a procedure under Article 107 of Directive 2001/83/EC6 August 2010 EMA/808179/2009 rev EMEA/H/A-107/1256 [home page on the Internet] Europeian medicines Agency(EMA) [cited August 2010]. Available at: http:// www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Sibutramine_107/WC500094238.pdf (accessed September 7, 2015).
43. Curfman G., Morrissey S., Drazen J. Sibutramine – Another Flawed Diet Pill. New England J. of Medicine. 2010; 363(10): 972–974. DOI: 10.1056/nejme1007993.
44. Williams G. Withdrawal of sibutramine in Europe. BMJ. 2010; 340(feb09 3): c824–c824. DOI: 10.1136/bmj.c824.
45. Zhi J., Melia A., Eggers H., Joly R., Patel I. Review of Limited Systemic Absorption of Orlistat, a Lipase Inhibitor, in Healthy Human Volunteers. The J. of Clinical Pharmacology. 1995; 35(11): 1103–1108. DOI: 10.1002/j.1552-4604.1995.tb04034.x.
46. Torgerson J., Hauptman J., Boldrin M., Sjostrom 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. 2003; 27(1): 155–161. DOI: 10.2337/diacare.27.1.155.
47. Toplak H., Ziegler O., Keller U. et al. X-PERT: weight reduction with orlistat in obese subjects receiving a mildly or moderately reduced-energy diet. Early response to treatment predicts weight maintenance. Diabetes Obes. Metab. 2005; 7(6): 699–708. DOI: 10.1111/j.1463-1326.2005.00483.x.
48. Wirth A. Reduction of body weight and co-morbidities by orlistat: The XXL – Primary Health Care Trial. Diabetes Obes. Metab. 2005; 7(1): 21–27. DOI: 10.1111/j.1463-1326.2004.00428.x.
49. Biondi B. Thyroid and Obesity: An Intriguing Relationship. The J. of Clinical Endocrinology & Metabolism. 2010; 95(8): 3614–3617. DOI: 10.1210/jc.2010-1245.
50. Pucci E., Chiovato L., Pinchera A. Thyroid and lipid metabolism. Int. J. Obes. Relat. Metab. Disord. 2000; 24: S109–S112. DOI: 10.1038/sj.ijo.0801292.
51. Yanovski S., Yanovski J. Long-term Drug Treatment for Obesity. JAMA. 2014; 311(1): 74. DOI: 10.1001/jama.2013.281361.
52. Astrup A., Meier D., Mikkelsen B., Villumsen J., Larsen T. Weight Loss Produced by Tesofensine in Patients With Parkinsonʼs or Alzheimerʼs Disease. Obesity. 2008; 16(6): 1363–1369. DOI: 10.1038/oby.2008.56.
53. Astrup A., Madsbad S., Breum L., Jensen T., Kroustrup J., Larsen T. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. The Lancet. 2008; 372(9653): 1906–1913. DOI: 10.1016/s0140-6736(08)61525-1.
54. Doggrell S. Tesofensine – a novel potent weight loss medicine. Expert Opinion on Investigational Drugs. 2009; 18(7): 1043–1046. DOI: 10.1517/13543780902967632.
55. Thomsen W., Grottick A., Menzaghi F. et al. Lorcaserin, a Novel Selective Human 5-Hydroxytryptamine2C Agonist: in Vitro and in Vivo Pharmacological Characterization. J. of Pharmacology and Experimental Therapeutics. 2008; 325(2): 577–587. DOI: 10.1124/jpet.107.133348.
56. Arena Pharmaceuticals’ Lorcaserin for Obesity Passes Major Safety Milestone [home page in the Internet] Pipelinereview.com [cited March 2008]. Available at: (accessed September 7, 2015).
57. Smith S., Weissman N., Anderson C. et al. Multicenter, Placebo-Controlled Trial of Lorcaserin for Weight Management. New England J. of Medicine. 2010; 363(3): 245–256. DOI: 10.1056/nejmoa0909809.
58. Larkin M. Controversy over diet to “prevent cancer”. The Lancet. 1998; 352(9142): 1789. DOI: 10.1016/s0140-6736(05)79875-5.
59. Plodkowski R., Nguyen Q., Sundaram U., Nguyen L., Chau D., St Jeor S. Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity. Expert Opinion on Pharmacotherapy. 2009; 10(6): 1069–1081. DOI: 10.1517/14656560902775750.
60. Klein S., Wadden T., Erickson J., Kim D. et al. Naltrexone+bupropion combination causes significant weight loss without worsening psychiatric symptoms. Proceedings of 69th Annual Scientific Sessions of the American Diabetes Association, New Orleans, Louisiana, USA, June 5–9, 2009; 1730.
61. Allison D., Gadde K., Garvey W. et al. Controlled-Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (EQUIP). Obesity. 2011; 20(2): 330–342. DOI: 10.1038/oby.2011.330.
62. Gadde K., Allison D., Ryan D. 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. The Lancet. 2011; 377(9774): 1341–1352. DOI: 10.1016/s0140-6736(11)60205-5.
63. Garvey W., Ryan D., Look M. et al. Two-year sustained weight loss and metabolic benefits with controlledrelease phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebocontrolled, phase 3 extension study. American J. of Clinical Nutrition. 2011; 95(2): 297–308. DOI: 10.3945/ajcn.111.024927.
64. Bluher M. Clinical Relevance of Adipokines. Diabetes & Metabolism Journal. 2012; 36(5): 317. DOI: 10.4093/dmj.2012.36.5.317.
65. Bluher M. Adipokines-removing road blocks to obesity and diabetes therapy. Molecular Metabolism. 2014; 3(3): 230– 240. DOI: 10.1016/j.molmet.2014.01.005.
66. Bauche I., EI Mkadem S., Pottier A. et al. Overexpression of Adiponectin Targeted to Adipose Tissue in Transgenic Mice: Impaired Adipocyte Differentiation. Endocrinology. 2007; 148(4): 1539–1549. DOI: 10.1210/en.2006-0838.
67. Seoane L.M., Lopez M., Tovar S. et al. Agouti-Related Peptide, Neuropeptide Y, and Somatostatin-Producing Neurons Are Targets for Ghrelin Actions in the Rat Hypothalamus. Endocrinology. 2003; 144(2): 544–551. DOI: 10.1210/en.2002-220795.
68. Ahima R.S., Flier J.S. Leptin. Annu. Rev. Physiol. 2000; 62: 413–37.
69. Savage D.B., O’Rahilly S. Leptin: a novel therapeutic role in lipodystrophy. J. of Clinical Investigation. 2002; 109(10): 1285–1286. DOI: 10.1172/jci200215326.
70. Chou K., Perry C. Metreleptin: First Global Approval. Drugs. 2013; 73(9): 989–997. DOI: 10.1007/s40265-013-0074-7.
71. Muller T., Sullivan L., Habegger K. et al. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J. of Peptide Science. 2012; 18(6): 383–393. DOI: 10.1002/psc.2408.
72. Amylin and Takeda Discontinue Development of Pramlintide/Metreleptin combination treatment for obesity following commercial reassessment of the program [home page on the Internet] Amylin Pharmaceuticals, Inc. Takeda Pharmaceutical Company Limited [cited August 5, 2011]. Available at: http://www.takeda.com/news/2011/20110805_3889.html (accessed September 7, 2015).
73. Turer A., Scherer P. Adiponectin: mechanistic insights and clinical implications. Diabetologia. 2012; 55(9): 2319–2326. DOI: 10.1007/s00125-012-2598-x.
74. Kusminski C., Scherer P. The Road From Discovery to Clinic: Adiponectin as a Biomarker of Metabolic Status. Clin. Pharmacol. Ther. 2009; 86(6): 592–595. DOI: 10.1038/clpt.2009.155.
75. Okada-Iwabu M., Yamauchi T., Iwabu M. et al. A smallmolecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013; 503(7477): 493–499. DOI: 10.1038/nature12656.
76. Lotfy M., Singh J., Kalász H., Tekes K., Adeghate E. Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus. The Open Medicinal Chemistry J. 2011; 5(Suppl2): 82–92. DOI: 10.2174/1874104501105010082.
77. Oh-I S., Shimizu H., Satoh T. et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006; 443(7112): 709–712. DOI: 10.1038/nature05162.
78. Klöting N., Kovacs P., Kern M. et al. Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia. 2011; 54(7): 1819–1823. DOI: 10.1007/s00125-011-2137-1.
79. Saito M., Okamatsu-Ogura Y., Matsushita M. et al. High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans: Effects of Cold Exposure and Adiposity. Diabetes. 2009; 58(7): 1526–1531. DOI: 10.2337/db09-0530.
80. Canto C., Auwerx J. PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current Opinion in Lipidology. 2009; 20(2): 98–105. DOI: 10.1097/mol.0b013e328328d0a4.
81. Raschke S., Elsen M., Gassenhuber H. et al. Evidence against a beneficial effect of irisin in humans. PLoS One 2013 September 11; [cited September 11]; 8(9). Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073680 (accessed September 7, 2015).
82. Timmons J., Baar K., Davidsen P., Atherton P. Is irisin a human exercise gene? Nature. 2012; 488(7413): E9-E10. DOI: 10.1038/nature11364.
83. Tsigos C., Hainer V., Basdevant A. et al. Management of Obesity in Adults: European Clinical Practice Guidelines. Obesity Facts. 2008; 1(2): 106–116. DOI: 10.1159/000126822.
84. Aronne L., Wadden T., Peterson C., Winslow D., Odeh S., Gadde K. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity. 2013; 21(11): 2163–2171. DOI: 10.1002/oby.20584.
85. Kiortsis D. A review of the metabolic effects of controlledrelease Phentermine/Topiramate. HJ. 2013; 12(4): 507– 516. DOI: 10.14310/horm.2002.1438.
86. Caixas A., Albert L., Capel I., Rigla M. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. DDDT. 2014: 1419. DOI: 10.2147/dddt.s55587.
87. Greenway F., Whitehouse M., Guttadauria M. et al. Rational Design of a Combination Medication for the Treatment of Obesity. Obesity. 2009; 17(1): 30–39. DOI: 10.1038/oby.2008.461
88. Medication Guide Saxenda [home page on the Internet] Novo Nordisk [cited December 2014]. Available format: http://www.novo-pi.com/saxenda.pdf (accessed September 7, 2015).
89. Marks D., Pae C., Patkar A. Triple Reuptake Inhibitors: The Next Generation of Antidepressants. Current Neuropharmacology. 2008; 6(4): 338–343. DOI: 10.2174/157015908787386078.
90. Rascol O. Tesofensine (NS 2330), a Monoamine Reuptake Inhibitor, in Patients With Advanced Parkinson Disease and Motor Fluctuations. Arch Neurol. 2008; 65(5): 577. DOI: 10.1001/archneur.65.5.577.
91. Schoedel K., Meier D., Chakraborty B., Manniche P., Sellers E. Subjective and Objective Effects of the Novel Triple Reuptake Inhibitor Tesofensine in Recreational Stimulant Users. Clin. Pharmacol. Ther. 2010; 88(1): 69– 78. DOI: 10.1038/clpt.2010.67.
92. Bray G., Hollander P., Klein S. et al. A 6-Month Randomized, Placebo-Controlled, Dose-Ranging Trial of Topiramate for Weight Loss in Obesity. Obesity Research. 2003; 11(6): 722–733. DOI: 10.1038/oby.2003.102.
93. Phase 2 Results on Zafgenʼs Weight-Loss Drug Beloranib Released [home page on the Internet] Drug discovery & development [cited November 15, 2013]. Available at: http://www.dddmag.com/news/2013/11/phase-2-resultszafgens-weight-loss-drug-beloranib-released (accessed September 7, 2015).
Review
Views: 101
Email this article 