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New pharmacological approaches for obesity management

Nature Reviews Endocrinology volume 9, pages 467–478 (2013)Cite this article

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Abstract

Obesity, which results from an imbalance between calorie intake and expenditure, now affects over 500 million individuals worldwide. Lifestyle and behavioural interventions aimed at reducing calorie intake and/or increasing energy expenditure have limited long-term effectiveness due to complex and persistent hormonal, metabolic and neurochemical adaptations that defend against weight loss and promote weight regain. Surgical treatments for obesity, although highly effective, are unavailable or unsuitable for the majority of individuals with excess adiposity. Accordingly, few effective treatment options are available to most individuals with obesity. In the past, the use of antiobesity drugs, seemingly the logical choice to fill this therapeutic gap, has been limited because of a lack of efficacy, poor long-term adherence rates and serious adverse effects. In 2012, the FDA approved two new medications—lorcaserin and phentermine–topiramate controlled release—and is currently reviewing the resubmission of naltrexone sustained release–bupropion sustained release. This Review presents the available data on the efficacy and safety of these three medications and discusses future perspectives and challenges related to pharmacological weight management.

Key Points

  • Lifestyle interventions for obesity rarely result in sustained weight loss and are generally characterized by high rates of recidivism or weight regain

  • The primary aim of pharmacological treatments for obesity is to suppress the biological drivers of weight gain and dampen the biological counter-response to weight loss

  • Emerging medications show promise for obtaining clinically relevant weight loss as well as improvements in comorbidities

  • Further studies are needed to assess the long-term benefits and cost-effectiveness of these new agents

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Figure 1: Absolute and placebo-adjusted weight loss after 1 year of treatment with lorcaserin, naltrexone SR–bupropion SR or phentermine–topiramate CR in phase III clinical trials.

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Acknowledgements

C. F. Rueda-Clausen's research is supported by the Canadian Institute of Health Research and Alberta Innovates Health Solutions. A. M. Sharma's and R. S. Padwal's research is supported by an alternative funding plan from the Government of Alberta, Canada, and the University of Alberta, Canada. A. M. Sharma is the Alberta Health Services Chair in Obesity Research and Management.

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Authors and Affiliations

  1. Department of Medicine, Obesity Research & Management, Alberta Diabetes Institute, Faculty of Medicine & Dentistry, University of Alberta, Li Ka Shing Building, 87th Avenue and, 112th Street, Edmonton, T6G 2E1, AB, Canada

    Christian F. Rueda-Clausen, Raj S. Padwal & Arya M. Sharma

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Contributions

C. F. Rueda-Clausen researched the data for the article. C. F. Rueda-Clausen, R. S. Padwal and A. M. Sharma contributed substantially to discussions of content, writing, review and/or editing the manuscript before submission.

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Correspondence to Arya M. Sharma.

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Competing interests

R. S. Padwal has acted as a consultant for VIVUS Pharmaceutical. A. M. Sharma has acted as a consultant for Arena Pharmaceutical, Orexigen Therapeutics and VIVUS Pharmaceutical in relation to their antiobesity drug programs. C. F. Rueda-Clausen declares no competing interests.

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Rueda-Clausen, C., Padwal, R. & Sharma, A. New pharmacological approaches for obesity management. Nat Rev Endocrinol 9, 467–478 (2013). https://doi.org/10.1038/nrendo.2013.113

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