J Korean Med Assoc.  2015 May;58(5):452-457. 10.5124/jkma.2015.58.5.452.

New and emerging drugs for the treatment of obesity

• Roh E
• Kim MS

• KMID: 2195041
• DOI: http://doi.org/10.5124/jkma.2015.58.5.452

Abstract

Obesity has become a global public health problem. The importance of obesity is highlighted by the fact that obesity-related comorbidities, such as type 2 diabetes, cardiovascular disease, and cancer, are a leading cause of death in Westernized countries. As endorsement of lifestyle modifications has proven to be inadequate to combat obesity, pharmacological treatment has become more critical for weight reduction as well as for the treatment of obesity-related morbidity and mortality. However, safety issues dampened the success of the development of anti-obesity drugs, leaving orlistat as the single approved drug for long-term weight management until 2012, when two new anti-obesity drugs were approved by the FDA: lorcaserin and phentermine/topiramate. In 2014, another two drugs were approved by the US FDA for the treatment of obesity: naltrexone/bupropion and liraglutide. In this review, we describe the new FDA-approved anti-obesity drugs and briefly introduce other anti-obesity drugs still under development.

Keyword

Obesity; Drug; Development

MeSH Terms

Anti-Obesity Agents
Cardiovascular Diseases
Cause of Death
Comorbidity
Life Style
Liraglutide
Mortality
Obesity*
Public Health
Weight Loss
Anti-Obesity Agents

Reference

1. World Health Organization. Obesity: preventing and managing the global epidemic: report of a WHO consultation. Geneva: World Health Organization;2000.

2. Kim CS, Ko SH, Kwon HS, Kim NH, Kim JH, Lim S, Choi SH, Song KH, Won JC, Kim DJ, Cha BY. Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Prevalence, awareness, and management of obesity in Korea: data from the Korea national health and nutrition examination survey (1998-2011). Diabetes Metab J. 2014; 38:35–43.

3. Tsigos C, Hainer V, Basdevant A, Finer N, Fried M, Mathus-Vliegen E, Micic D, Maislos M, Roman G, Schutz Y, Toplak H, Zahorska-Markiewicz B. Obesity Management Task Force of the European Association for the Study of Obesity. Management of obesity in adults: European clinical practice guidelines. Obes Facts. 2008; 1:106–116.

4. James WP. The epidemiology of obesity: the size of the problem. J Intern Med. 2008; 263:336–352.

5. Plodkowski RA, St Jeor ST. Medical nutrition therapy for the treatment of obesity. Endocrinol Metab Clin North Am. 2003; 32:935–965.

6. Hensrud DD. Pharmacotherapy for obesity. Med Clin North Am. 2000; 84:463–476.

7. Bassett J. International Diabetes Institute. World Health Organization. Regional Office for the Western Pacific. International Association for the Study of Obesity. International Obesity Task Force. The Asia-Pacific perspective: redefining obesity and its treatment. Australia: Health Communications Australia;2000.

8. 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.

9. 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.

10. Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, Whelan K, Martin M, Morgan M, Chen W, Al-Shamma H, Smith B, Chalmers D, Behan D. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther. 2008; 325:577–587.

11. 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. BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010; 363:245–256.

12. O'Neil PM, Smith SR, Weissman NJ, Fidler MC, Sanchez M, Zhang J, Raether B, Anderson CM, Shanahan WR. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring). 2012; 20:1426–1436.

13. Astrup A, Toubro S. Topiramate: a new potential pharmacological treatment for obesity. Obes Res. 2004; 12:Suppl. 167S–173S.

14. Gadde KM, Allison DB. Combination pharmaceutical therapies for obesity. Expert Opin Pharmacother. 2009; 10:921–925.

15. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, Day WW. 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; 377:1341–1352.

16. Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, Schwiers M, Day WW, Bowden CH. 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; 95:297–308.

17. Ornellas T, Chavez B. Naltrexone SR/Bupropion SR (Contrave): a new approach to weight loss in obese adults. P T. 2011; 36:255–262.

18. 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.

19. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998; 101:515–520.

20. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996; 379:69–72.

21. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rossner S, Savolainen MJ, Van Gaal L. NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012; 36:843–854.

22. Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, Aronne L. NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after lowcalorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013; 37:1443–1451.

23. Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther. 2011; 90:40–51.

24. 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.

25. Sjodin A, Gasteyger C, Nielsen AL, Raben A, Mikkelsen JD, Jensen JK, Meier D, Astrup A. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes (Lond). 2010; 34:1634–1643.

26. 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.

27. Hughes TE, Kim DD, Marjason J, Proietto J, Whitehead JP, Vath JE. Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women. Obesity (Silver Spring). 2013; 21:1782–1788.