Top

Published in:

01-06-2013 | Hypertension and Obesity (E Reisin, Section Editor)

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

Authors: Donna H. Ryan, George A. Bray

Published in: Current Hypertension Reports | Issue 3/2013

Abstract

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.

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

Decision Memo for Intensive Behavioral Therapy for Obesity (CAG-00423 N). http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?&NcaName=Intensive%20Behavioral%20Therapy%20for%20Obesity&bc=ACAAAAAAIAAA&NCAId=253.

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].

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

13.

Bray GA. Do we need drugs to treat the patient with obesity? Obesity. 2013 (in press).

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.PubMedCrossRef

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.PubMedCrossRef

16.

FDA briefing information: meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. 2012. (http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM292315.pdf).

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 approval – lorcaserin and phentermine/topiramate (extended release).PubMedCrossRef

18.

Brownell KD. The LEARN manual for weight management. Dallas: American Health Publishing Co; 2000.

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.PubMedCrossRef

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.PubMed

21.

Rothman RB, Baumann MH. Serotonergic drugs and valvular heart disease. Expert Opin Drug Saf. 2009;8:317–29.PubMedCrossRef

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.PubMedCrossRef

23.

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.PubMedCrossRef

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. PubMedCrossRef

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.

Contrave (Naltrexone SR/Bupropion SR Combination) Advisory Committee Briefing Document. NDA 200063. Endocrinologic and Metabolic Drugs Advisory Committee Meeting, December 7, 2010.

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.PubMedCrossRef

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.PubMedCrossRef

30.

http://www.accessdata.fda.gov/drugsaftfda_docs/label/2011/202088s001lbl.pdf.

31.

VI-0521 (QNEXA®) Advisory Committee Briefing Document. NDA 022580. Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2010. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM292317.pdf. Accessed 15 March 2012.

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.CrossRef

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.CrossRef

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.PubMedCrossRef

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.PubMedCrossRef

Title: Pharmacologic Treatment Options for Obesity: What Is Old Is New Again
Authors: Donna H. Ryan
George A. Bray
Publication date: 01-06-2013
Publisher: Current Science Inc.
Published in: Current Hypertension Reports / Issue 3/2013
Print ISSN: 1522-6417
Electronic ISSN: 1534-3111
DOI: https://doi.org/10.1007/s11906-013-0343-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2013

Ambulatory Blood Pressure in Stroke and Cognitive Dysfunction

Evidence of Clinically Relevant Efficacy for Dietary Supplements and Nutraceuticals

High Blood Pressure: The Leading Global Burden of Disease Risk Factor and the Need for Worldwide Prevention Programs

Obstructive Sleep Apnea and Hypertension: Is the Primary Link Simply Volume Overload?

Exercise Training and Cardiometabolic Diseases: Focus on the Vascular System

Obesity and Metabolic Syndrome in Kidney Transplantation

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials