Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity
- 707 Downloads
Obesity is a growing epidemic in the USA with over one third of adults presently classified as obese. Obesity-related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and certain types of cancer. Modest weight loss of 5–10 % of body weight is sufficient to produce clinically relevant improvements in cardiovascular disease risk factors among patients with overweight and obesity. Until recently, there were limited pharmacologic options approved by the Food and Drug Administration to treat obesity. Phentermine/topiramate ER and lorcaserin were approved in 2012, and naltrexone SR/bupropion SR and liraglutide 3.0 mg were approved in 2014. This article reviews recent literature in the field of Obesity Medicine and highlights important findings from clinical trials. Future directions in the pharmacologic management of obesity are presented along with new diabetes medications that promote weight loss and reduce cardiovascular mortality.
KeywordsObesity Weight loss Weight management Pharmacotherapy Clinical trials Type 2 diabetes
Compliance with Ethical Standards
Conflict of Interest
Katherine H. Saunders and Leon I. Igel declare that they have no conflict of interest.
Rekha B. Kumar declares personal fees for being a speaker for Jansen Pharmaceuticals and is a shareholder in Zafgen and Myos Corporation.
Louis J. Aronne declares consultant/advisory board work with Jamieson Labs, Pfizer Inc, Novo Nordisk A/S, Eisai, VIVUS, GI Dynamics, JOVIA Health, and Gelesis. He is a shareholder of Zafgen, Gelesis, Myos Corporation, and Jamieson Labs, and he is on the Board of Directors of MYOS Corporation and Jamieson Labs. He has received research funding from Aspire Bariatrics and Eisai.
Human and Animal Rights and Informed Consent
All studies by Louis J. Aronne involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written, informed consent was obtained from all participants.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.Magkos F, Fraterrigo G, Yoshino J. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;S1550-4131(16):30053–5.Google Scholar
- 15.••Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63((25 Pt B)):2985–3023. This publication denotes the first clinical practice guidelines for the management of adults with overweight and obesity. These guidelines were drafted by a task force of experts from the American College of Cardiology, American Heart Association and The Obesity Society.CrossRefPubMedGoogle Scholar
- 16.••Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342–62. This publication denotes the first clinical practice guidelines for the pharmacologic management of obesity. These guidelines were drafted by an Endocrine Society-appointed task force of experts, and were co-sponsored by the European Society of Endocrinology and The Obesity Society.CrossRefPubMedGoogle Scholar
- 17.American Medical Association. Policy H-440.842. Recognition of Obesity as a Disease. 2013.Google Scholar
- 19.Gadde KM, Allison DB, Ryan DH, 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.CrossRefPubMedGoogle Scholar
- 27.Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36(12):4022–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Nauck M, Frid A, Hermansen K, et al. 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(1):84–90.CrossRefPubMedPubMedCentralGoogle Scholar
- 36.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(9):1782–8.Google Scholar
- 38.Zafgen Inc. Zafgen’s pivotal phase 3 trial of beloranib in Prader-Willi syndrome achieves co-primary efficacy endpoints. http://ir.zafgen.com/releasedetail.cfm?ReleaseID=950876. Accessed February 26, 2016.
- 39.Zafgen Inc. Zafgen announces positive results from phase 2 clinical trial of beloranib in hypothalamic injury associated obesity. http://ir.zafgen.com/releasedetail.cfm?releaseid=889999. Accessed March 8, 2016.
- 40.Zafgen, Inc. Zafgen provides clinical update on Beloranib. http://ir.zafgen.com/releasedetail.cfm?releaseid=945102. Accessed February 26, 2016.
- 41.Lomaira KVK Tech, Inc. http://kvktech.com/lomaira/ Accessed Feburary 27, 2016.
- 42.Smith SR, Garvey WT, Greenway F, et al. Combination Weight Management (WM) Pharmacotherapy with Lorcaserin (LOR) and Immediate Release (IR) Phentermine (phen) [abstract]. Poster presented at Obesity Week. Boston; 2014.Google Scholar
- 43.Aronne LJ. A practical guide to drug-induced weight gain. Minneapolis: McGraw-Hill; 2002.Google Scholar
- 44.Top-Line Data Show CV Benefit for Liraglutide in Type 2 Diabetes. Miriam E Tucker. Medscape Medical News. WebMD LLC. http://www.medscape.com/viewarticle/859905. Accessed March 8, 2016.
- 45.•Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. EMPA-REG OUTCOME is the first trial investigating a medication for type 2 diabetes which demonstrates both weight loss and improved cardiovascular outcomes in high-risk patients.CrossRefPubMedGoogle Scholar
- 49.Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–9.CrossRefPubMedGoogle Scholar