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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Current Options for the Pharmacotherapy of Obesity

Author(s): Ioanna Gouni-Berthold* and Heiner K. Berthold

Volume 25, Issue 18, 2019

Page: [2019 - 2032] Pages: 14

DOI: 10.2174/1381612825666190708192630

Price: $65

Abstract

650 millions of adults are obese worldwide - in the US alone, forty percent of the adults are obese. Although the obesity pandemic is constantly expanding at very high costs for health care systems, the currently available options of pharmacotherapy for obesity are rather limited. Despite intensive research efforts, the vast majority of the anti-obesity drugs developed up to now have a rather limited efficacy and/or safety profile. In the last fifty years, various drugs reached advanced states of clinical development but were either never marketed or were initially approved but withdrawn later due to safety issues. However, the understanding of the pathophysiology of obesity has been steadily improving and new, promising drugs targeting various selective obesityassociated and energy-homeostasis-related pathways are now available. When lifestyle changes alone fail to combat, then additional pharmacotherapy with an acceptable efficacy and safety profile could provide a useful therapeutic option.

Keywords: Obesity, anti-obesity drugs, weight loss, body mass index, pharmacotherapy, energy-homeostasis-related pathways.

[1]
Gregg EW, Shaw JE. Global health effects of overweight and obesity. N Engl J Med 2017; 377(1): 80-1.
[http://dx.doi.org/10.1056/NEJMe1706095] [PMID: 28604226]
[2]
Afshin A, Forouzanfar MH, Reitsma MB, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017; 377(1): 13-27.
[http://dx.doi.org/10.1056/NEJMoa1614362] [PMID: 28604169]
[3]
Pilitsi E, Farr OM, Polyzos SA, et al. Pharmacotherapy of obesity: Available medications and drugs under investigation. Metabolism 2018.
[http://dx.doi.org/10.1016/j.metabol.2018.10.010] [PMID: 30391259]
[4]
Sassi F. Obesity and the economics of prevention: Fit not fat. Paris: OECD Publishing 2010.
[http://dx.doi.org/10.4337/9781849808620]
[5]
Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 2011; 378(9793): 815-25.
[http://dx.doi.org/10.1016/S0140-6736(11)60814-3] [PMID: 21872750]
[6]
Watts G. The future of obesity treatment: What can drugs and surgery offer? BMJ 2012; 344: e1011.
[http://dx.doi.org/10.1136/bmj.e1011] [PMID: 22334541]
[7]
Jensen MD, Ryan DH, Apovian CM, et al. 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. J Am Coll Cardiol 2014; 63(25 Pt B): 2985-3023.
[http://dx.doi.org/10.1016/j.jacc.2013.11.004] [PMID: 24239920]
[8]
Srivastava G, Apovian C. Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon. Curr Obes Rep 2018; 7(2): 147-61.
[http://dx.doi.org/10.1007/s13679-018-0300-4] [PMID: 29504049]
[9]
Kotsis V, Jordan J, Micic D, et al. Obesity and cardiovascular risk: A call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part A: mechanisms of obesity induced hypertension, diabetes and dyslipidemia and practice guidelines for treatment. J Hypertens 2018; 36(7): 1427-40.
[http://dx.doi.org/10.1097/HJH.0000000000001730] [PMID: 29634663]
[10]
Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther 2011; 90(1): 40-51.
[http://dx.doi.org/10.1038/clpt.2011.82] [PMID: 21654742]
[11]
Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. BMC Med 2016; 14(1): 191.
[http://dx.doi.org/10.1186/s12916-016-0735-y] [PMID: 27894343]
[12]
Kushner RF. Weight loss strategies for treatment of obesity: Lifestyle management and pharmacotherapy. Prog Cardiovasc Dis 2018; 61(2): 246-52.
[http://dx.doi.org/10.1016/j.pcad.2018.06.001] [PMID: 29890171]
[13]
Lim S, Rogers LK, Tessler O, Mundinger GS, Rogers C, Lau FH. Phentermine: A Systematic Review for Plastic and Reconstructive Surgeons. Ann Plast Surg 2018; 81(4): 503-7.
[http://dx.doi.org/10.1097/SAP.0000000000001478] [PMID: 30204622]
[14]
Coulter AA, Rebello CJ, Greenway FL. Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs 2018; 78(11): 1113-32.
[http://dx.doi.org/10.1007/s40265-018-0946-y] [PMID: 30014268]
[15]
Rothman RB, Baumann MH. Appetite suppressants, cardiac valve disease and combination pharmacotherapy. Am J Ther 2009; 16(4): 354-64.
[http://dx.doi.org/10.1097/MJT.0b013e31817fde95] [PMID: 19092640]
[16]
Rothman RB, Baumann MH, Dersch CM, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001; 39(1): 32-41.
[http://dx.doi.org/10.1002/1098-2396(20010101)39:1<32:AID-SYN5>3.0.CO;2-3] [PMID: 11071707]
[17]
Velazquez A, Apovian CM. Updates on obesity pharmacotherapy. Ann N Y Acad Sci 2018; 1411(1): 106-19.
[http://dx.doi.org/10.1111/nyas.13542] [PMID: 29377198]
[18]
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.
[http://dx.doi.org/10.3349/ymj.2006.47.5.614] [PMID: 17066505]
[19]
Munro JF, MacCuish AC, Wilson EM, Duncan LJ. Comparison of continuous and intermittent anorectic therapy in obesity. BMJ 1968; 1(5588): 352-4.
[http://dx.doi.org/10.1136/bmj.1.5588.352] [PMID: 15508204]
[20]
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.
[http://dx.doi.org/10.1111/j.1463-1326.2010.01242.x] [PMID: 20920040]
[21]
Moldovan CP, Weldon AJ, Daher NS, et al. Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings. Obesity (Silver Spring) 2016; 24(11): 2344-50.
[http://dx.doi.org/10.1002/oby.21649] [PMID: 27664021]
[22]
Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy 2000; 20(3): 270-9.
[http://dx.doi.org/10.1592/phco.20.4.270.34882] [PMID: 10730683]
[23]
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(1): 155-61.
[http://dx.doi.org/10.2337/diacare.27.1.155] [PMID: 14693982]
[24]
Weir MA, Beyea MM, Gomes T, et al. Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med 2011; 171(7): 703-4.
[http://dx.doi.org/10.1001/archinternmed.2011.103] [PMID: 21482850]
[25]
Dossabhoy NR, McRight S, Sangha B, Khan S, Adgeh C. Orlistat-induced oxalate nephropathy may be dose-independent and present as a late manifestation. J La State Med Soc 2013; 165(5): 283-5.
[PMID: 24350530]
[26]
Garvey WT, Mechanick JI, Brett EM, et al. American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity Endocr Pract 2016; 22(Supply 3): 1-203.
[http://dx.doi.org/10.4158/EP161365.GL]
[27]
Patel DK, Stanford FC. Safety and tolerability of new-generation anti-obesity medications: a narrative review. Postgrad Med 2018; 130(2): 173-82.
[http://dx.doi.org/10.1080/00325481.2018.1435129] [PMID: 29388462]
[28]
Chao AM, Wadden TA, Berkowitz RI. The safety of pharmacologic treatment for pediatric obesity. Expert Opin Drug Saf 2018; 17(4): 379-85.
[http://dx.doi.org/10.1080/14740338.2018.1437143] [PMID: 29411652]
[29]
Padwal R. Cetilistat, a new lipase inhibitor for the treatment of obesity. Curr Opin Investig Drugs 2008; 9(4): 414-21.
[PMID: 18393108]
[30]
Kopelman P, Bryson A, Hickling R, et al. Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients. Int J Obes 2007; 31(3): 494-9.
[http://dx.doi.org/10.1038/sj.ijo.0803446] [PMID: 16953261]
[31]
Kopelman P, Groot Gde H, Rissanen A, et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity (Silver Spring) 2010; 18(1): 108-15.
[http://dx.doi.org/10.1038/oby.2009.155] [PMID: 19461584]
[32]
Aronne LJ, Powell AG, Apovian CM. Emerging pharmacotherapy for obesity. Expert Opin Emerg Drugs 2011; 16(3): 587-96.
[http://dx.doi.org/10.1517/14728214.2011.609168] [PMID: 21834735]
[33]
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[34]
DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005; 28(5): 1092-100.
[http://dx.doi.org/10.2337/diacare.28.5.1092] [PMID: 15855572]
[35]
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(9701): 1606-16.
[http://dx.doi.org/10.1016/S0140-6736(09)61375-1] [PMID: 19853906]
[36]
Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes 2012; 36(6): 843-54.
[http://dx.doi.org/10.1038/ijo.2011.158] [PMID: 21844879]
[37]
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. Int J Obes 2013; 37(11): 1443-51.
[http://dx.doi.org/10.1038/ijo.2013.120] [PMID: 23812094]
[38]
Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA 2015; 314(7): 687-99.
[http://dx.doi.org/10.1001/jama.2015.9676] [PMID: 26284720]
[39]
Blackman A, Foster GD, Zammit G, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes 2016; 40(8): 1310-9.
[http://dx.doi.org/10.1038/ijo.2016.52] [PMID: 27005405]
[40]
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(1): 11-22.
[http://dx.doi.org/10.1056/NEJMoa1411892] [PMID: 26132939]
[41]
le Roux CW, Astrup A, Fujioka K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 2017; 389(10077): 1399-409.
[http://dx.doi.org/10.1016/S0140-6736(17)30069-7] [PMID: 28237263]
[42]
Ard J, Cannon A, Lewis CE, et al. Efficacy and safety of liraglutide 3.0 mg for weight management are similar across races: subgroup analysis across the SCALE and phase II randomized trials. Diabetes Obes Metab 2016; 18(4): 430-5.
[http://dx.doi.org/10.1111/dom.12632] [PMID: 26744025]
[43]
Davies MJ, Aronne LJ, Caterson ID, Thomsen AB, Jacobsen PB, Marso SP. Liraglutide and cardiovascular outcomes in adults with overweight or obesity: A post hoc analysis from SCALE randomized controlled trials. Diabetes Obes Metab 2018; 20(3): 734-9.
[http://dx.doi.org/10.1111/dom.13125] [PMID: 28950422]
[44]
Drucker DJ, Sherman SI, Bergenstal RM, Buse JB. The safety of incretin-based therapies-review of the scientific evidence. J Clin Endocrinol Metab 2011; 96(7): 2027-31.
[http://dx.doi.org/10.1210/jc.2011-0599] [PMID: 21734003]
[45]
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375(19): 1834-44.
[http://dx.doi.org/10.1056/NEJMoa1607141] [PMID: 27633186]
[46]
O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet 2018; 392(10148): 637-49.
[http://dx.doi.org/10.1016/S0140-6736(18)31773-2] [PMID: 30122305]
[47]
Lam DD, Przydzial MJ, Ridley SH, et al. Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology 2008; 149(3): 1323-8.
[http://dx.doi.org/10.1210/en.2007-1321] [PMID: 18039773]
[48]
Smith BM, Smith JM, Tsai JH, et al. Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J Med Chem 2008; 51(2): 305-13.
[http://dx.doi.org/10.1021/jm0709034] [PMID: 18095642]
[49]
Rothman RB, Baumann MH, Savage JE, et al. Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 2000; 102(23): 2836-41.
[http://dx.doi.org/10.1161/01.CIR.102.23.2836] [PMID: 11104741]
[50]
Launay JM, Hervé P, Peoc’h K, et al. Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med 2002; 8(10): 1129-35.
[http://dx.doi.org/10.1038/nm764] [PMID: 12244304]
[51]
Smith SR, Prosser WA, Donahue DJ, Morgan ME, Anderson CM, Shanahan WR. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity (Silver Spring) 2009; 17(3): 494-503.
[http://dx.doi.org/10.1038/oby.2008.537] [PMID: 19057523]
[52]
Martin CK, Redman LM, Zhang J, et al. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab 2011; 96(3): 837-45.
[http://dx.doi.org/10.1210/jc.2010-1848] [PMID: 21190985]
[53]
Thomsen WJ, Grottick AJ, Menzaghi F, 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.
[http://dx.doi.org/10.1124/jpet.107.133348] [PMID: 18252809]
[54]
Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363(3): 245-56.
[http://dx.doi.org/10.1056/NEJMoa0909809] [PMID: 20647200]
[55]
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(10): 3067-77.
[http://dx.doi.org/10.1210/jc.2011-1256] [PMID: 21795446]
[56]
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(7): 1426-36.
[http://dx.doi.org/10.1038/oby.2012.66] [PMID: 22421927]
[57]
Bohula EA, Wiviott SD, McGuire DK, et al. Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med 2018; 379(12): 1107-17.
[http://dx.doi.org/10.1056/NEJMoa1808721] [PMID: 30145941]
[58]
Bohula EA, Scirica BM, Inzucchi SE, et al. Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial. Lancet 2018; 392(10161): 2269-79.
[http://dx.doi.org/10.1016/S0140-6736(18)32328-6] [PMID: 30293771]
[59]
Unamuno X, Frühbeck G. Lorcaserin: balancing efficacy with potential risks. Lancet 2018; 392(10161): 2239-40.
[http://dx.doi.org/10.1016/S0140-6736(18)32460-7] [PMID: 30293772]
[60]
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(12): 4898-906.
[http://dx.doi.org/10.1210/jc.2009-1350] [PMID: 19846734]
[61]
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(9741): 595-605.
[http://dx.doi.org/10.1016/S0140-6736(10)60888-4] [PMID: 20673995]
[62]
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(1): 110-20.
[http://dx.doi.org/10.1038/oby.2010.147] [PMID: 20559296]
[63]
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(5): 935-43.
[http://dx.doi.org/10.1002/oby.20309] [PMID: 23408728]
[64]
Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 2013; 36(12): 4022-9.
[http://dx.doi.org/10.2337/dc13-0234] [PMID: 24144653]
[65]
Davidson J. Seizures and bupropion: a review. J Clin Psychiatry 1989; 50(7): 256-61.
[PMID: 2500425]
[66]
Beyens MN, Guy C, Mounier G, Laporte S, Ollagnier M. Serious adverse reactions of bupropion for smoking cessation: analysis of the French Pharmacovigilance Database from 2001 to 2004. Drug Saf 2008; 31(11): 1017-26.
[http://dx.doi.org/10.2165/00002018-200831110-00006] [PMID: 18840021]
[67]
Thase ME, Haight BR, Johnson MC, et al. A randomized, double-blind, placebo-controlled study of the effect of sustained-release bupropion on blood pressure in individuals with mild untreated hypertension. J Clin Psychopharmacol 2008; 28(3): 302-7.
[http://dx.doi.org/10.1097/JCP.0b013e318172424e] [PMID: 18480687]
[68]
Astrup A. Is cardiometabolic risk improved by weight-loss drugs? Lancet 2010; 376(9741): 567-8.
[http://dx.doi.org/10.1016/S0140-6736(10)60999-3] [PMID: 20673996]
[69]
McCubbin JA, Bruehl S, Wilson JF, Sherman JJ, Norton JA, Colclough G. Endogenous opioids inhibit ambulatory blood pressure during naturally occurring stress. Psychosom Med 1998; 60(2): 227-31.
[http://dx.doi.org/10.1097/00006842-199803000-00020] [PMID: 9560874]
[70]
Katsiki N, Hatzitolios AI, Mikhailidis DP. Naltrexone sustained-release (SR) + bupropion SR combination therapy for the treatment of obesity: ‘a new kid on the block’? Ann Med 2011; 43(4): 249-58.
[http://dx.doi.org/10.3109/07853890.2010.541490] [PMID: 21254901]
[71]
Billes SK, Greenway FL. Combination therapy with naltrexone and bupropion for obesity. Expert Opin Pharmacother 2011; 12(11): 1813-26.
[http://dx.doi.org/10.1517/14656566.2011.591382] [PMID: 21689063]
[72]
Saleh AA, El-Magd MA. Beneficial effects of dietary silver nanoparticles and silver nitrate on broiler nutrition. Environ Sci Pollut Res Int 2018; 25(27): 27031-8.
[http://dx.doi.org/10.1007/s11356-018-2730-7] [PMID: 30014368]
[73]
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(10): 990-1004.
[http://dx.doi.org/10.1001/jama.2016.1558] [PMID: 26954408]
[74]
Bray GA, Ryan DH. Drug treatment of obesity. Psychiatr Clin North Am 2011; 34(4): 871-80.
[http://dx.doi.org/10.1016/j.psc.2011.08.013] [PMID: 22098810]
[75]
Müller TD, Clemmensen C, Finan B, DiMarchi RD, Tschöp MH. Anti-obesity therapy: From rainbow pills to polyagonists. Pharmacol Rev 2018; 70(4): 712-46.
[http://dx.doi.org/10.1124/pr.117.014803] [PMID: 30087160]
[76]
Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring) 2013; 21(11): 2163-71.
[http://dx.doi.org/10.1002/oby.20584] [PMID: 24136928]
[77]
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(6): 722-33.
[http://dx.doi.org/10.1038/oby.2003.102] [PMID: 12805393]
[78]
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 2004; 28(11): 1399-410.
[http://dx.doi.org/10.1038/sj.ijo.0802783] [PMID: 15486569]
[79]
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(9774): 1341-52.
[http://dx.doi.org/10.1016/S0140-6736(11)60205-5] [PMID: 21481449]
[80]
Garvey WT, Ryan DH, Henry R, et al. Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care 2014; 37(4): 912-21.
[http://dx.doi.org/10.2337/dc13-1518] [PMID: 24103901]
[81]
Garvey WT, Ryan DH, Bohannon NJ, et al. Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended release. Diabetes Care 2014; 37(12): 3309-16.
[http://dx.doi.org/10.2337/dc14-0930] [PMID: 25249652]
[82]
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(2): 330-42.
[http://dx.doi.org/10.1038/oby.2011.330] [PMID: 22051941]
[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(2): 297-308.
[http://dx.doi.org/10.3945/ajcn.111.024927] [PMID: 22158731]
[84]
Mullard A. Panel meeting prompts excitement for antiobesity drug. Lancet 2012; 379(9819): 882.
[http://dx.doi.org/10.1016/S0140-6736(12)60379-1] [PMID: 22413140]
[85]
Dong Z, Xu L, Liu H, Lv Y, Zheng Q, Li L. Comparative efficacy of five long-term weight loss drugs: Quantitative information for medication guidelines. Obes Rev 2017; 18(12): 1377-85.
[http://dx.doi.org/10.1111/obr.12606] [PMID: 29024559]
[86]
Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA 2016; 315(22): 2424-34.
[http://dx.doi.org/10.1001/jama.2016.7602] [PMID: 27299618]
[87]
Wise J. Weight loss drugs are compared for effectiveness. BMJ 2016; 353: i3330.
[http://dx.doi.org/10.1136/bmj.i3330] [PMID: 27307315]

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