CB1 antagonists for obesity—what lessons have we learned from rimonabant? (original) (raw)

Nature Reviews Endocrinology volume 5, pages 633–638 (2009)Cite this article

Abstract

When compared with other modifiable cardiovascular risk factors, such as hypertension, dyslipidemia and smoking, obesity remains a surprisingly puzzling condition to prevent and treat. The history of the development of anti-obesity drugs has known more defeats than even partial victories. With very few drugs on the market, and bad publicity related to adverse events, obesity remains an almost completely unmet challenge for the pharmaceutical industry. In light of past experience with endocannabinoid-system antagonists, such as rimonabant, we propose that a major paradigm shift in clinical practice might be necessary to justify the use of pharmacotherapy for obesity. Furthermore, we suggest that the criteria currently used by regulatory authorities to evaluate and approve anti-obesity drugs should be rigorously re-examined. Finally, we discuss how pharmacological approaches that aim to counteract overactivity of the endocannabinoid system should be revisited in the future to treat visceral (intra-abdominal) obesity and its metabolic consequences.

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Figure 1: Endocannabinoid biosynthesis, action and inactivation.

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Acknowledgements

The authors thank Isabelle Lemieux (Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada) for valuable help during preparation of the manuscript.

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Authors and Affiliations

  1. Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Pozzuoli, Italy
    Vincenzo Di Marzo
  2. Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada
    Jean-Pierre Després

Authors

  1. Vincenzo Di Marzo
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  2. Jean-Pierre Després
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Correspondence toVincenzo Di Marzo.

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Competing interests

Vincenzo Di Marzo has declared associations with the following companies: GW Pharmaceuticals (consultant and research support) and Sanofi-Aventis (speakers bureau and research support).

Jean-Pierre Després has declared associations with the following companies: Abbott Laboratories (speakers bureau), AstraZeneca (speakers bureau), Eli Lilly (research support), GlaxoSmithKline (speakers bureau and research support), INNODIA (consultant), Merck Sharp & Dohme (consultant), Novartis (consultant), Pfizer Canada (speakers bureau), Sanofi-Aventis (consultant, speakers bureau and research support) and Solvay (speakers bureau).

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Di Marzo, V., Després, JP. CB1 antagonists for obesity—what lessons have we learned from rimonabant?.Nat Rev Endocrinol 5, 633–638 (2009). https://doi.org/10.1038/nrendo.2009.197

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