Current Hypertension Reports

, Volume 15, Issue 3, pp 182–189 | Cite as

Pharmacologic Treatment Options for Obesity: What Is Old Is New Again

  • Donna H. Ryan
  • George A. BrayEmail author
Hypertension and Obesity (E Reisin, Section Editor)


After a long period of failure in development, two new medications (phentermine/topiramate ER – Qsymia™ and lorcaserin – Belviq®) have been approved by the US Food and Drug Administration for long-term weight management in persons with obesity (BMI ≥ 30 kg/m2) or in overweight persons (BMI ≥ 27 kg/m2) with comorbidities. Another medication, bupropion/naltrexone, is undertaking a cardiovascular outcomes trial and an analysis in 2014 will determine its approval and release. The most widely prescribed drug for obesity, phentermine, used since 1959 for short-term weight management, has been released in a new formulation. This paper reviews these new medications, and other important events in the landscape for management of obesity, with an eye to the interests of physicians who manage hypertension. All the new drugs under discussion are re-fittings of old agents or fresh approaches to old targets; thus, what is old is new again in the pharmacotherapy of obesity.


Obesity Hypertension Pharmacotherapy Obesity treatment Medications for obesity Phentermine Topiramate Topiramate ER Lorcaserin Naltrexone Bupropion Qsymia Belviq Contrave Suprenza 


Conflict of Interest

D.H. Ryan has received research funding from Arena, Vivus, and Orexigen; consulting fees from Arena, Vivus, Esai, and Scientific Intake; travel support from Arena, Vivus, and Esai; payment for serving as a board member from Novo Nordisk, Scientific Intake, and Alere Wellbeing; and stock options from Scientific Intake.

G.A. Bray has received research funding from National Institutes of Health; consulting fees from Takeda Global Development; payment for lectures including service on speakers bureaus from Medifast and Global Direction in Medicine; and royalties from CRC Press.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Look AHEAD Research Group, Pi-Sunyer X, Blackburn G, Brancati FL, Bray GA, Bright R, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the Look AHEAD trial. Diabetes Care. 2007;30(6):1374–83.PubMedCrossRefGoogle Scholar
  2. 2.
    Look AHEAD Research Group, Wing RR, et al. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170(17):1566–75.PubMedCrossRefGoogle Scholar
  3. 3.
    Foster GD, Borradaile KE, Sanders MH, Millman R, Zammit G, Newman AB, et al. A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD Study. Arch Intern Med. 2009;169(17):1619–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Phelan S, Kanaya A, Subak L, Hogan P, Espeland MA, Wing RR, et al. Weight loss prevents urinary incontinence in women with type 2 diabetes: results from the Look AHEAD trial. J Urol. 2012;187(3):939–44.PubMedCrossRefGoogle Scholar
  5. 5.
    Rubin RR, Gaussoin SA, Peyrot M, DiLillo V, Miller K, Wadden TA, et al. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetologia. 2010;53(8):1581–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Rejeski J, Ip E, Bertoni A, Bray G, Evans G, Gregg E, et al. Lifestyle change and mobility in obese adults with type 2 diabetes. N Engl J Med. 2012;366(13):1209–17.PubMedCrossRefGoogle Scholar
  7. 7.
    Redmon JB, Bertoni AG, Connelly S, Feeney PA, Glasser SP, Glick H, et al. Effect of the look AHEAD study intervention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes. Diabetes Care. 2010;33(6):1153–8.PubMedCrossRefGoogle Scholar
  8. 8.
  9. 9.
    Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial: a prospective controlled intervention study of bariatric surgery. J Int Med. 2012. doi: 10.1111/joim.12012 [Epub ahead of print].Google Scholar
  10. 10.
    Schauer PR, Kashyap SR, Wolski K, Brethauer SG, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Mingrone G, Panunzi S, DeGaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366:1577–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Cohen RV, Pnheiro JC, Schiavon CA, Salles JE, Wajchenberg BL, Cummings DE. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care. 2012;35:1420–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Bray GA. Do we need drugs to treat the patient with obesity? Obesity. 2013 (in press).Google Scholar
  14. 14.
    • Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20(2):330–42. This was one of the two pivotal Phase III clinical trials that underpinned the approval of phentermine/topiramte (extended release) by the U.S. Food and Drug Administration.PubMedCrossRefGoogle Scholar
  15. 15.
    • Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, 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. This was the other one of the two pivotal Phase III clinical trials that underpinned the approval of phentermine/topiramate (extended release) by the U.S. Food and Drug Administration.PubMedCrossRefGoogle Scholar
  16. 16.
    FDA briefing information: meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. 2012. (
  17. 17.
    •• Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. 2012;367:1577–9. In this paper, Colman and colleagues provide comparative data on the weight losses for the two drugs that received U.S. Food and Drug Administration approvallorcaserin and phentermine/topiramate (extended release).PubMedCrossRefGoogle Scholar
  18. 18.
    Brownell KD. The LEARN manual for weight management. Dallas: American Health Publishing Co; 2000.Google Scholar
  19. 19.
    •• Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, 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;95:297–308. This paper describes the two-year trial extending the treatment for people who completed the study described in # 15. It provides the two-year weight loss data showing that both the recommended dose and the top dose were associated with maintenance of almost all of their initial weight loss up to 2 years. In addition, there were significant improvements in almost all of the cardiometabolic risk factors.PubMedCrossRefGoogle Scholar
  20. 20.
    Winslow DH, Bowden CH, DiDonato KP, McCullough PA. A randomized, double-blind, placebo-controlled study of an oral, extended-release formulation of phentermine/topiramate for the treatment of obstructive sleep apnea in obese adults. Sleep. 2012;35(11):1529–39.PubMedGoogle Scholar
  21. 21.
    Rothman RB, Baumann MH. Serotonergic drugs and valvular heart disease. Expert Opin Drug Saf. 2009;8:317–29.PubMedCrossRefGoogle Scholar
  22. 22.
    Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE. Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs. 2007;67:27–55.PubMedCrossRefGoogle Scholar
  23. 23.
    FDA briefing information: meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. 2012. (
  24. 24.
    •• Smith SR, Weissman NJ, Anderson CM Sanchez M, Chuang E, Stubbe S, Bays H, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245–56. This is one of the pivotal Phase III studies of lorcaserin that was used to obtain approval from the U.S. FDA.PubMedCrossRefGoogle Scholar
  25. 25.
    • Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. was significantly greater than with placebo. J Clin Endocrinol Metab. 2011;96:3067–77. This is another pivotal Phase III studies of lorcaserin that was used to obtain approval from the U.S. FDA. PubMedCrossRefGoogle Scholar
  26. 26.
    • 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(7):1426–36. doi: 10.1038/oby.2012.66. Epub 2012 Mar 16. This randomized clinical trial shows that lorcaserin significantly reduced body weight and improved cardiometabolic risk factors in patients with diabetes mellitus.
  27. 27.
    Contrave (Naltrexone SR/Bupropion SR Combination) Advisory Committee Briefing Document. NDA 200063. Endocrinologic and Metabolic Drugs Advisory Committee Meeting, December 7, 2010.Google Scholar
  28. 28.
    Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicenter, randomised, double = blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595–605.PubMedCrossRefGoogle Scholar
  29. 29.
    Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O’Neil PM, et al. Weight loss with naltrexoneSR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011;19:110–20.PubMedCrossRefGoogle Scholar
  30. 30.
  31. 31.
    VI-0521 (QNEXA®) Advisory Committee Briefing Document. NDA 022580. Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2010. Accessed 15 March 2012.
  32. 32.
    Ryan D, Peterson C, Troupin B, Najarian T, Tam P, Day W. Weight loss at 6 months with VI-0521 (PHEN/TPM combination) treatment. Obes Facts. 2010;3:139–46.CrossRefGoogle Scholar
  33. 33.
    Kang JG, Park C-Y, Kang JH, Park Y-W, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obesity Metab. 2010;12:876–82.CrossRefGoogle Scholar
  34. 34.
    Addy C, Rosko JP, Li S, Li H, Maes A, Johnson-Levonas AO, et al. Pharmacokinetics, safety, and tolerability of phentermine in healthy participants receiving taranabant, a novel cannabinoid-1 receptor (CB1R) inverse agonist. J Clin Pharmacol. 2009;49(10):1228–38.PubMedCrossRefGoogle Scholar
  35. 35.
    Kim KK, Cho H-J, Kang J-C, Youn B-B, Lee K-R. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people. Yonsei Med J. 2006;47(5):614–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Pennington Biomedical Research CenterBaton RougeUSA

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