Diabetes Metab J.  2012 Feb;36(1):13-25. 10.4093/dmj.2012.36.1.13.

Anti-Obesity Drugs: A Review about Their Effects and Safety

Affiliations
  • 1Department of Endocrinology and Metabolism, Hallym University Sacred Heart Hospital, Hallym University School of Medicine, Anyang, Korea.
  • 2Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. cydoctor@chol.com

Abstract

The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

Keyword

Anti-obesity agents; Obesity; Safety

MeSH Terms

Amphetamine
Anti-Obesity Agents
Appetite
Body Weight
Cyclobutanes
Lactones
Licensure
Motor Activity
Myocardial Infarction
Obesity
Piperidines
Pyrazoles
Stroke
Amphetamine
Anti-Obesity Agents
Cyclobutanes
Lactones
Piperidines
Pyrazoles

Cited by  2 articles

A Case of Phendimetrazine Induced-Psychotic Disorder and Dependence
Ji-Ae Yun, Wu-Ri Park, Je-Chun Yu, Kyeong-Sook Choi
J Korean Neuropsychiatr Assoc. 2013;52(5):402-405.    doi: 10.4306/jknpa.2013.52.5.402.

Effects of anti-obesity drugs, phentermine and mahuang, on the behavioral patterns in Sprague-Dawley rat model
Ryeo-Eun Go, Kyung-A Hwang, Seung-Hee Kim, Min-Young Lee, Cho-Won Kim, So-Ye Jeon, Yun-Bae Kim, Kyung-Chul Choi
Lab Anim Res. 2014;30(2):73-78.    doi: 10.5625/lar.2014.30.2.73.


Reference

1. James WP. The epidemiology of obesity: the size of the problem. J Intern Med. 2008. 263:336–352.
2. Park HS, Park CY, Oh SW, Yoo HJ. Prevalence of obesity and metabolic syndrome in Korean adults. Obes Rev. 2008. 9:104–107.
3. National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med. 2000. 160:898–904.
4. 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:Suppl 2. 51S–209S.
5. Kaukua J, Pekkarinen T, Sane T, Mustajoki P. Health-related quality of life in obese outpatients losing weight with very-low-energy diet and behaviour modification: a 2-y follow-up study. Int J Obes Relat Metab Disord. 2003. 27:1072–1080.
6. Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, Schaff HV. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997. 337:581–588.
7. Glazer G. Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety. Arch Intern Med. 2001. 161:1814–1824.
8. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007. 370:1706–1713.
9. Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther. 2011. 90:40–51.
10. Ioannides-Demos LL, Proietto J, Tonkin AM, McNeil JJ. Safety of drug therapies used for weight loss and treatment of obesity. Drug Saf. 2006. 29:277–302.
11. James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL. SCOUT Investigators. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010. 363:905–917.
12. Vetter ML, Faulconbridge LF, Webb VL, Wadden TA. Behavioral and pharmacologic therapies for obesity. Nat Rev Endocrinol. 2010. 6:578–588.
13. Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, Hilton L, Suttorp M, Solomon V, Shekelle PG, Morton SC. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005. 142:532–546.
14. Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord. 2002. 26:262–273.
15. 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. 12:876–882.
16. Cercato C, Roizenblatt VA, Leanca CC, Segal A, Lopes Filho AP, Mancini MC, Halpern A. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects. Int J Obes (Lond). 2009. 33:857–865.
17. Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. 2004. 3:771–784.
18. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005. 365:1389–1397.
19. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J. RIO-North America Study Group. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006. 295:761–775.
20. Despres JP, Golay A, Sjostrom L. Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005. 353:2121–2134.
21. Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF. RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006. 368:1660–1672.
22. Samat A, Tomlinson B, Taheri S, Thomas GN. Rimonabant for the treatment of obesity. Recent Pat Cardiovasc Drug Discov. 2008. 3:187–193.
23. Aronne LJ, Tonstad S, Moreno M, Gantz I, Erondu N, Suryawanshi S, Molony C, Sieberts S, Nayee J, Meehan AG, Shapiro D, Heymsfield SB, Kaufman KD, Amatruda JM. A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study. Int J Obes (Lond). 2010. 34:919–935.
24. Addy C, Wright H, Van Laere K, Gantz I, Erondu N, Musser BJ, Lu K, Yuan J, Sanabria-Bohorquez SM, Stoch A, Stevens C, Fong TM, De Lepeleire I, Cilissen C, Cote J, Rosko K, Gendrano IN 3rd, Nguyen AM, Gumbiner B, Rothenberg P, de Hoon J, Bormans G, Depre M, Eng WS, Ravussin E, Klein S, Blundell J, Herman GA, Burns HD, Hargreaves RJ, Wagner J, Gottesdiener K, Amatruda JM, Heymsfield SB. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab. 2008. 7:68–78.
25. Proietto J, Rissanen A, Harp JB, Erondu N, Yu Q, Suryawanshi S, Jones ME, Johnson-Levonas AO, Heymsfield SB, Kaufman KD, Amatruda JM. A clinical trial assessing the safety and efficacy of the CB1R inverse agonist taranabant in obese and overweight patients: low-dose study. Int J Obes (Lond). 2010. 34:1243–1254.
26. Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007. 335:1194–1199.
27. Park CY, Kim YS, Ryu MS, Nam SY, Park HS, Kim SM. A phase 3 double-blind, parallel-group, placebo-controlled trial of the efficacy and safety of sibutramine (Reductil) in the treatment of obese patients. J Korean Soc Study Obes. 2001. 10:336–347.
28. Nisoli E, Carruba MO. An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action. Obes Rev. 2000. 1:127–139.
29. Mannucci E, Dicembrini I, Rotella F, Rotella CM. Orlistat and sibutramine beyond weight loss. Nutr Metab Cardiovasc Dis. 2008. 18:342–348.
30. Bosello O, Carruba MO, Ferrannini E, Rotella CM. Sibutramine lost and found. Eat Weight Disord. 2002. 7:161–167.
31. Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, Maggioni A, Sharma A, Brisco W, Deaton R, Shepherd G, James P. SCOUT Investigators. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial. Eur Heart J. 2007. 28:2915–2923.
32. Astrup A. Drug management of obesity: efficacy versus safety. N Engl J Med. 2010. 363:288–290.
33. Harrison-Woolrych M, Ashton J, Herbison P. Fatal and non-fatal cardiovascular events in a general population prescribed sibutramine in New Zealand: a prospective cohort study. Drug Saf. 2010. 33:605–613.
34. Rossner S, Sjostrom L, Noack R, Meinders AE, Noseda G. European Orlistat Obesity Study Group. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res. 2000. 8:49–61.
35. Torgerson JS, Hauptman J, Boldrin MN, 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. 2004. 27:155–161.
36. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999. 281:235–242.
37. Chon S, Park C, Koh G, Oh S, Woo JT, Kim SW, Kim JW, Kim YS, Son HY, Cha BY, Yoon KH, Kwon HS, Cha BS, Lee HC. The effect of orlistat in obese patients with type 2 diabetes: benefit on abdominal obesity and glycemic control. J Korean Soc Study Obes. 2004. 13:281–292.
38. Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev. 2004. CD004094.
39. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, Bays H, Shanahan WR. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010. 363:245–256.
40. Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, Anderson CM. BLOSSOM Clinical Trial Group. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011. 96:3067–3077.
41. Briefing information for the September 16, 2010 meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. U.S. Food and Drug Administration. updated 2010 Sep 14. Available from: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/ucm225628.htm.
42. Arena and Eisai complete end-of-review meeting with FDA for Lorcaserin new drug application. Arena Pharmaceuticals. updated 2010 Dec 22. Available from: http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=538430.
43. Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, Taylor KL, Trautmann ME, Kim DD, Kendall DM. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006. 8:436–447.
44. Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR. LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009. 32:84–90.
45. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007. 298:194–206.
46. Meade LT, Tackett KL, McKeever AL. Practical use of exenatide and pramlintide for the treatment of type 2 diabetes. J Pharm Pract. 2009. 22:540–545.
47. Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME. NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009. 374:1606–1616.
48. Significant weight loss sustained in obese people treated with liraglutide for one year. Novo Nordisk. updated 2008 Jun 16. Available from: http://www.novonordisk.com/investors/sea/sea.asp?sShowNewsItemGuID=34d7e084-1d6b-4b78-bb9e-f0bf70920b0a&sShowLanguageCode=en-GB&sSearchText=Liraglutide+AND+obesity.
49. Astrup A, Meier DH, Mikkelsen BO, Villumsen JS, Larsen TM. Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease. Obesity (Silver Spring). 2008. 16:1363–1369.
50. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008. 372:1906–1913.
51. NeuroSearch successfully completes End of Phase II meeting with the FDA for tesofensine, a treatment for obesity. NeuroSearch. updated 2009 Jun 8. Available from: https://newsclient.omxgroup.com/cdsPublic/viewDisclosure.action?disclosureId=329924&messageId=396203.
52. Kopelman P, Groot Gde H, Rissanen A, Rossner S, Toubro S, Palmer R, Hallam R, Bryson A, Hickling RI. 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. 18:108–115.
53. Glandt M, Raz I. Present and future: pharmacologic treatment of obesity. J Obes. 2011. 2011:636181.
54. Kaya A, Aydin N, Topsever P, Filiz M, Ozturk A, Dagar A, Kilinc E, Ekmekcioglu C. Efficacy of sibutramine, orlistat and combination therapy on short-term weight management in obese patients. Biomed Pharmacother. 2004. 58:582–587.
55. Qnexa meets primary endpoint by demonstrating superior weight loss over components and placebo in the 28-week equate study (OB-301). Vivus. updated 2008 Dec 11. Available from: http://ir.vivus.com/releasedetail.cfm?ReleaseID=353965.
56. Vivus announces positive results from two phase 3 studies; obese patients on Qnexa achieve average weight loss up to 14.7% and significant improvements in co-morbidities. Vivus. cited 2009 Sep 9. Available from: http://ir.vivus.com/releasedetail.cfm?ReleaseID=407933.
57. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E. COR-I Study Group. 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. 376:595–605.
58. Orexigen (R) therapeutics presents new data showing contrave (R) significantly lowers weight, improves blood glucose control in obese patients with type 2 diabetes. Orexigen Therapeutics Inc. cited 2010 Jun 25. Available from: http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle_print&ID=1441827&highlight=.
59. Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O'Neil PM, Perri MG, Pi-Sunyer FX, Rock CL, Erickson JS, Maier HN, Kim DD, Dunayevich E. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011. 19:110–120.
Full Text Links
  • DMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr