The Obesity Epidemic: Current and Future Pharmacological Treatments

Annual Review of Pharmacology and Toxicology - Tập 47 Số 1 - Trang 565-592 - 2007
Karl G. Hofbauer1, Janet R. Nicholson1, Olivier Boss2
1Applied Pharmacology, Biozentrum/Pharmazentrum, University of Basel, CH 4056 Basel, Switzerland;
2Sirtris Pharmaceuticals Inc., Cambridge, Massachusetts 02139

Tóm tắt

The unabated rise in the prevalence of obesity is a challenge for global health care systems. Efforts to reverse this trend by dietary or behavioral counseling have not been successful, which has stimulated efforts to find a role for pharmacotherapy. Currently only a small number of antiobesity drugs are approved for long-term use and only a few compounds are in clinical development. Despite recent progress in the understanding of the regulation of energy balance, drug discovery has been less productive than expected. In the present review, the clinically available antiobesity agents are discussed. Examples of drug candidates that are currently in development are given and the possible future range of antiobesity agents is illustrated by the targets being addressed in drug discovery. Finally, the efficacy of antiobesity agents and their value in the treatment of obesity are assessed in comparison with other therapeutic approaches, such as surgery and changes in lifestyle.

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Tài liệu tham khảo

10.1001/jama.291.23.2847

10.1016/S0140-6736(05)67483-1

10.1093/ije/dyi272

10.1038/nm0106-62

10.1146/annurev.publhealth.26.021304.144415

10.7326/0003-4819-142-1-200501040-00012

10.7326/0003-4819-142-7-200504050-00012

10.1152/japplphysiol.00137.2005

10.1016/j.ahj.2005.03.005

10.1038/nm0604-563

10.1152/japplphysiol.00757.2003

10.1210/jc.2004-0906

10.1016/S0169-5347(02)02515-6

10.1056/NEJMoa021423

10.1126/science.1104342

10.1161/CIRCULATIONAHA.106.171016

10.1016/j.physbeh.2005.08.050

10.1056/NEJMoa012512

10.1161/01.HYP.0000165680.59733.d4

10.1146/annurev.med.56.082103.104751

10.1161/CIRCULATIONAHA.105.169404

10.2337/diacare.28.9.2289

10.1046/j.1467-789X.2003.00122.x

10.1038/oby.2004.251

10.1046/j.1467-789X.2001.00043.x

10.2165/00002018-199920020-00003

10.1056/NEJMra012586

10.1161/01.CIR.99.1.156

10.1016/j.ahj.2005.03.006

10.1056/NEJMoa040135

10.1016/S0165-6147(00)01664-3

10.2174/1389450043345191

10.1038/oby.2004.151

10.1016/j.phrs.2004.02.004

10.1210/jc.2004-0341

10.1016/S0092-8674(03)01081-X

10.1016/j.ahj.2005.03.007

10.1038/clpt.1994.104

Hauner H. 2004. Orlistat. See Ref. 127, pp.219–43

10.2165/00003495-200464240-00010

10.1001/jama.281.3.235

10.1001/archinte.164.9.994

Ryan DH. 2004. Sibutramine. See Ref. 127, pp.245–66

10.1007/s10286-005-0270-y

10.1038/nn1457

10.1038/sj.bjp.0706406

10.1016/S0140-6736(05)66374-X

10.1001/jama.295.7.761

10.1001/jama.295.7.826

10.1056/NEJMoa044537

10.1161/01.HYP.0000094221.86888.AE

10.1016/S0735-1097(01)01671-0

10.1161/01.CIR.0000143230.23252.D2

10.1016/j.jada.2005.03.010

Dulloo AG. 2004. Dietary supplements and herbal preparations. See Ref. 127, pp.405–19

Greenway FL, 2004, Handbook of Obesity, 329

10.1126/science.1109951

10.1126/science.1104344

10.1126/science.299.5608.849

10.1210/en.2004-1150

10.2337/diabetes.53.suppl_3.S233

10.1016/S1054-3589(05)52006-4

10.1038/372425a0

10.1016/j.physbeh.2004.02.014

10.1001/jama.282.16.1568

10.1038/nm1071

10.1016/j.ejphar.2003.08.089

10.1073/pnas.0509240102

10.1038/nn1455

10.1038/nm0404-351

10.1161/01.HYP.0000048194.97428.1A

10.1016/j.peptides.2005.01.026

10.1016/j.peptides.2004.11.035

10.1038/sj.ijir.3901139

10.1016/j.cell.2005.08.035

10.1677/joe.1.05866

10.1007/s00125-005-0107-1

10.1016/j.regpep.2004.02.006

10.1111/j.1467-789X.2005.00218.x

10.1056/NEJMoa030204

10.1016/j.regpep.2004.08.007

10.2174/1389450053174569

10.1172/JCI27999

Harper ME, Dent R, Tesson F, McPherson R. 2004. Targeting thermogenesis in the development of antiobesity drugs. See Ref. 127, pp.363–83

10.1210/me.2004-0193

10.1620/tjem.192.181

10.2337/diabetes.49.2.143

10.2337/diabetes.53.2007.S136

10.1038/oby.2003.192

10.1146/annurev.pharmtox.45.120403.095843

10.1016/S1359-6446(05)03569-5

10.1517/14728222.10.1.119

10.1038/ncpcardio0380

10.1038/sj.ijo.0802908

10.1007/s00125-005-1956-3

10.1093/jn/134.9.2455S

10.1161/01.ATV.0000151874.81059.ad

10.1210/en.142.12.5182

10.1038/nm1048

10.1210/en.2003-0580

10.7326/0003-4819-142-7-200504050-00013

10.1001/jama.294.15.1960

10.1210/jc.2004-0433

10.1056/NEJM199503093321001

10.1073/pnas.061034298

10.1001/jama.289.14.1826

10.1126/science.1115360

10.1038/nn1453

10.1113/expphysiol.2003.026740

10.1097/00000441-198804000-00018

10.1210/en.2002-221045

10.1126/science.1069881

10.1056/NEJMoa050156

10.1038/sj.ijo.0803290

Summerbell CD, Waters E, Edmunds LD, Kelly S, Brown T, Campbell KJ. 2005. Interventions for preventing obesity in children. Cochrane Database Syst. Rev. 3:CD001871.pub2.DOI:10.1002/14651858.CD001871.pub2

10.1038/oby.2004.282

Hofbauer KG, Nicholson JR. 2006. Pharmacotherapy of obesity. J. Exp. Clin. Endocrinol. Diabetes. In press

10.1001/jama.295.13.1539

10.1093/toxsci/52.2.56

10.1210/jc.2002-020405

10.1111/j.1365-201X.2005.01466.x

10.1196/annals.1297.074

10.1038/nrm1616

10.1038/scientificamerican0306-48

10.1038/nature02789

10.1101/gad.1164804

10.1201/9780203508756