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  • Review Article
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Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?

Nature Reviews Clinical Oncology volume 14, pages 85–99 (2017)Cite this article

Subjects

Key Points

  • The incidences of obesity, type 2 diabetes mellitus (T2DM), and many cancers are rapidly increasing worldwide; clinicians are increasingly required to treat patients with both T2DM and cancer, or both obesity and cancer

  • Obesity is a risk factor for some cancers, and obesity at and weight gain after diagnosis are associated with adverse cancer outcomes; the interactions of diabetes and/or its treatments with cancer risk and outcomes are complex and controversial

  • Laboratory findings provide a rationale for clinical trials of the antidiabetic drug metformin for cancer treatment; although the first two studies (in pancreatic cancer) revealed no survival benefit, many additional studies are ongoing

  • Concerns about an increased cancer risk associated with other antidiabetic agents have been raised; in general, follow-up studies have failed to confirm such risks, but data on long-term exposure remain sparse and pharmacovigilance is necessary

  • Certain drugs used in the treatment of cancer lead to metabolic toxicities, chiefly hyperglycaemia, which might be dose-limiting for some patients, especially those with pre-existing diabetes

  • Clarification of the mechanisms underlying the relationships between obesity and neoplasia might provide clues relevant to novel cancer treatments and prevention strategies

Abstract

The prevalence of obesity, of type 2 diabetes mellitus (T2DM), and of cancer are all increasing globally. The relationships between these diseases are complex, and thus difficult to elucidate; nevertheless, evidence supports the hypothesis that obesity increases the risks of both T2DM and certain cancers. Further complexity arises from controversial evidence that specific drugs used in the treatment of T2DM increase or decrease cancer risk or influence cancer prognosis. Herein, we review the current evidence from studies that have addressed these relationships, and summarize the methodological challenges that are frequently encountered in such research. We also outline the physiology that links obesity, T2DM, and neoplasia. Finally, we outline the practical principles relevant to the increasingly common challenge of managing patients who have been diagnosed with both diabetes and cancer.

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Figure 1: Simplified representation of the physiological processes that might link obesity, diabetes, and neoplasia.
Figure 2: Clinical vignette and putative causal relationships between obesity, diabetes, antidiabetic medications, cancer, and cancer treatments.

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Acknowledgements

We thank Rhoda Lim (Cancer Prevention Centre, Jewish General Hospital, Montreal, Quebec, Canada) for excellent editorial assistance.

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  1. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Ste-Catherine Road, Montreal, H3T 1E2, Quebec, Canada

    Adi J. Klil-Drori & Laurent Azoulay

  2. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Purvis Hall, 1020 Pine Avenue West, Montreal, H3A 1A2, Quebec, Canada

    Adi J. Klil-Drori & Laurent Azoulay

  3. Departments of Oncology and Medicine, McGill University, McIntyre Medical Building, 3655 Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada

    Laurent Azoulay & Michael N. Pollak

  4. Segal Cancer Centre, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montreal, H3T 1E2, Quebec, Canada

    Michael N. Pollak

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A.J.K.-D. and M.N.P. researched data for the article and wrote the manuscript. All authors contributed to discussions of content, and reviewed and/or edited the manuscript before submission.

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Correspondence to Michael N. Pollak.

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Klil-Drori, A., Azoulay, L. & Pollak, M. Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?. Nat Rev Clin Oncol 14, 85–99 (2017). https://doi.org/10.1038/nrclinonc.2016.120

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