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EDITORIAL
Year : 2020  |  Volume : 10  |  Issue : 3  |  Page : 147-148  

Obesity treatment – Is pharmacotherapy the answer?


Obesity Medicine Specialist, Ascension Medical Group, Appleton, WI, USA

Date of Submission09-Mar-2020
Date of Decision23-Mar-2020
Date of Acceptance02-Jun-2020
Date of Web Publication11-Jul-2020

Correspondence Address:
Aditya Kumar Rangbulla
Ascension Medical Group, 1501 S Madison Street, Appleton 54915, WI
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijabmr.IJABMR_113_20

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How to cite this article:
Rangbulla AK. Obesity treatment – Is pharmacotherapy the answer?. Int J App Basic Med Res 2020;10:147-8

How to cite this URL:
Rangbulla AK. Obesity treatment – Is pharmacotherapy the answer?. Int J App Basic Med Res [serial online] 2020 [cited 2020 Sep 21];10:147-8. Available from: http://www.ijabmr.org/text.asp?2020/10/3/147/289466



More than 2 billion adults worldwide (39%) are overweight; of these adults, more than 650 million (13%) are obese, according to the World Health Organization. In the United States alone, recent studies suggest that more than 40% of adults are obese.[1] Exercise, diet, and behavior modification remain the cornerstone of treatment.[2] However, many affected patients cannot lose weight or maintain weight loss with that approach. Hence, medical and surgical options (e.g., bariatric surgery) have been developed to reduce and maintain weight loss. Among the patients who are considering their options, the long-term safety of any weight-loss regimen is critical to its widespread acceptance and adherence.

Clinical experience with the first generation of anti-obesity drugs was not encouraging, despite successful weight loss, because of side effects. In particular, agents such as dexfenfluramine and fenfluramine stimulated 5-hydroxytryptamine 2B (5-HT2B) serotonin receptors, which led to pulmonary hypertension and heart valve problems. Other medications such as orlistat, liraglutide, naltrexone-sustained release with bupropion-sustained release, and lorcaserin have provided additional options, but questions persist about their long-term safety.[3]

In obesity, a weight loss of 5%–10% can significantly improve risk factors for obesity-related diseases[4] and delay or prevent type 2 diabetes in persons at high risk.[5] Behavioral treatments can result in a weight loss sufficient to improve health for many patients, but often, the weight is regained over time. For many people, reduction in weight is difficult to achieve; however, maintaining the weight loss is even harder. Hence, there is a need for adjunctive treatments that can assist patients with carrying out the changes in lifestyle needed to produce and sustain weight loss. Weight-loss medications are available and many medications are approved by the Food and Drug Administration for weight loss.

The history of weight-loss medications is checkered. When amphetamines were approved for the treatment of obesity in the 1960s, obesity drugs were labeled only for short-term use. In 1992, a series of seminal articles by Weintraub showed the feasibility of treating obesity with long-term forms of core therapy similar to treatments for other diseases. The usefulness of such an approach was apparent to those who had long noted that weight loss was rarely sustained after weight-loss drugs were withdrawn. The two drugs, used in combination were fenfluramine and phentermine, effectively known as Fen/Phen, had been on the market for years and were believed to be safe and effective. Not long afterward, dexfenfluramine, which had been in use in Europe for more than a decade, became the first drug approved for long-term treatment of obesity in the United States.[6] The use of Fen/Phen and dexfenfluramine exploded despite nagging concerns about the adverse effect of pulmonary hypertension with approximately 14 million prescriptions written for either fenfluramine or dexfenfluramine from 1995 until the withdrawal of these drugs from the market in 1997.[7]

Drugs used to treat obesity differ from medications for other chronic diseases in how they are used. Obesity is a visible and stigmatizing condition. Few people want to be obese, and obese persons often have tried numerous times and with a variety of methods to lose weight. Because of the social emphasis on thinness, weight loss is also frequently attempted by people whose weight is normal or only slightly above normal. Therefore, a drug that appears to be efficacious in reducing body weight will undoubtedly be used not only to reduce medical risk among those who are obese but also to improve appearance among those less likely to have a medical benefit from weight loss. Thus, as Bray has suggested,[8] a careful assessment of safety of anti-obesity medications may be even more important than for drugs used to treat other conditions, in which the drugs are less liable to be misused. In addition, although weight loss in the obese persons is known to improve risk factors and might be anticipated to reduce cardiovascular morbidity and mortality, no study has yet demonstrated conclusively that any weight-loss medication treatment has such an effect. Research on this critical issue is ongoing.[6],[9],[10] Whether those who lose weight with anti-obesity medications have health outcomes similar to those who lose weight through lifestyle changes alone also remains uncertain.

How health-care professionals are going to make decisions with regard to use of anti-obesity medications in clinical practice? Overweight and obese patients should be carefully evaluated to assess their medical risk as well as their readiness to attempt weight loss. Although nondrug treatments should be the primary intervention, for many patients, attempts to lose weight or maintain weight loss through diet and exercise alone will not be sufficient. For patients whose weight and risk factors put them at high risk for obesity-related disease, physicians and patients may choose to initiate adjunctive treatment with anti-obesity medications. Weight-independent effects on such risk factors may be considered when choosing the appropriate medication as well as adverse effects, patient's preferences, and response to treatment. As Wadden made it clear,[11] the efficacy of drug therapy is markedly improved with the concomitant use of behavioral treatment. This finding is consistent with the National Institute of Health guidelines,[12] which recommend that weight-loss medications be used as a part of a comprehensive program that includes diet therapy and physical activity.

Improved therapeutic approaches are needed to promote and sustain weight loss safely and effectively in obese patients to treat and prevent many obesity-related conditions. Advances in our understanding of the complex systems regulating energy balance, the genetic determinants of obesity, and environmental factors that promote obesity should lead to not only the development of more effective and tolerated treatment options but also for primary prevention of obesity.



 
   References Top

1.
Obesity and Overweight. Geneva: World Health Organization; 2018. Available from: http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. [Last accessed 2020 Mar 09].  Back to cited text no. 1
    
2.
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, 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;63:2985-3023.  Back to cited text no. 2
    
3.
Saunders KH, Umashanker D, Igel LI, Kumar RB, Aronne LJ. Obesity Pharmacotherapy. Med Clin North Am 2018;102:135-48.  Back to cited text no. 3
    
4.
Clinical Guidelines on the Identification, Evaluation, and treatment of overweight and obesity in adults – The evidence report. National Institutes of Health. Obes Res 1998;6 Suppl 2:51S-209S.  Back to cited text no. 4
    
5.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.  Back to cited text no. 5
    
6.
Colman E. Anorectics on trial: A half century of federal regulation of prescription appetite suppressants. Ann Intern Med 2005;143:380-5.  Back to cited text no. 6
    
7.
Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health agnd Human Services interim public health recommendations; November 1997. MMWR Morb Mortal Wkly Rep 1997;46:1061-6.  Back to cited text no. 7
    
8.
Bray GA. Uses and misuses of the new pharmacotherapy of obesity. Ann Med 1999;31:1-3.  Back to cited text no. 8
    
9.
Sjöström CD. Surgery as an intervention for obesity. Results from the Swedish obese subjects study. Growth Horm IGF Res 2003;13 Suppl A:S22-6.  Back to cited text no. 9
    
10.
Ryan DH, Espeland MA, Foster GD, Haffner SM, Hubbard VS, Johnson KC, et al. Look AHEAD (Action for Health in Diabetes): Design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes. Control Clin Trials 2003;24:610-28.  Back to cited text no. 10
    
11.
Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005;353:2111-20.  Back to cited text no. 11
    
12.
Clinical Guidelines on the Identification, Evaluation, and treatment of overweight and obesity in adults – The evidence report. National Institutes of Health. Obes Res 1998;6 Suppl 2:51S-209S. In Erratum: Obes Res 1998;6:464.  Back to cited text no. 12
    




 

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