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Behavioral and pharmacologic therapies for obesity

Nature Reviews Endocrinology volume 6, pages 578–588 (2010)Cite this article

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Abstract

This article reviews novel developments in the behavioral and pharmacologic treatment of obesity and explores the potential contribution of genomics research to weight control. A comprehensive program of lifestyle modification, comprised of diet, physical activity and behavior therapy, induces a mean loss of 7–10% of initial weight in individuals with obesity. Two trials demonstrated that weight loss of this magnitude, combined with increased physical activity, substantially reduced the risk of developing type 2 diabetes mellitus in individuals with impaired glucose tolerance. A third trial is now investigating whether lifestyle intervention will reduce cardiovascular morbidity and mortality in overweight individuals who already have diabetes mellitus. Pharmacotherapy is recommended, in some patients, as an adjunct to lifestyle modification. Two medications—orlistat and sibutramine—are currently approved in the US for long-term weight loss. Both are efficacious when combined with lifestyle modification, although health concerns have been raised about the use of sibutramine. Several novel combination therapies, which target multiple hypothalamic pathways that regulate appetite and body weight, are currently under investigation. Genomic studies provide further evidence for the role of these pathways in the regulation of body weight. Identification of new genes controlling satiety and energy expenditure may yield valuable clues for the development of novel pharmacologic treatments.

Key Points

  • Lifestyle modification (behavioral weight management) is the first step to reduce obesity, as recommended by the WHO and the NIH

  • Weight losses of 7–10% of initial weight are typically achieved, but patients regain one-third of lost weight in the first year after treatment

  • Low-carbohydrate, low-fat and low glycemic index diets have all been shown to be effective, but reducing the number of calories ingested is the best predictor of weight loss

  • Sibutramine and orlistat are the only FDA-approved drugs for long-term weight loss, whereas medications such as phentermine are approved for short-term weight loss

  • Monogenic mutations that cause marked obesity, such as mutations in the leptin receptor, are well-established but very rare, indicating that obesity is probably the result of polygenic mutations

  • Genome-wide association studies have so far identified at least three new candidate genes as potential pharmacologic targets—fat mass and obesity associated (FTO), melanocortin receptor 4 (MC4R) and neuroendocrine convertase 1 (PCSK1)

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Figure 1: Neuronal control of energy intake.

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Acknowledgements

T. A. Wadden is supported by grant K24-DK065018 from the National Institute of Diabetes and Digestive and Kidney Diseases.

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  1. Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania School of Medicine, 3535 Market Street, Suite 3026, Philadelphia, 19104, PA, USA

    Marion L. Vetter, Lucy F. Faulconbridge, Victoria L. Webb & Thomas A. Wadden

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  1. Marion L. Vetter
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  2. Lucy F. Faulconbridge
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  3. Victoria L. Webb
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Contributions

All authors researched the data for the article and provided a substantial contribution to discussions of the content. M. L. Vetter, L. F. Faulconbridge and T. A. Wadden contributed to writing the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Thomas A. Wadden.

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Competing interests

T. A. Wadden declares an association with the following companies: Novo Nordisk (consultant, grant/research support), Orexigen Therapeutics (consultant, grant/research support), Vivus (consultant, grant/research support), Wyeth Pharmaceuticals (consultant). The other authors declare no competing interests.

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Vetter, M., Faulconbridge, L., Webb, V. et al. Behavioral and pharmacologic therapies for obesity. Nat Rev Endocrinol 6, 578–588 (2010). https://doi.org/10.1038/nrendo.2010.121

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