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Diabetes, antihyperglycemic medications and cancer risk: smoke or fire?

Gallagher, Emily J.; LeRoith, Derek

Current Opinion in Endocrinology, Diabetes and Obesity: October 2013 - Volume 20 - Issue 5 - p 485–494
doi: 10.1097/
Special Commentary

Objective The aim of this review article is to discuss the epidemiological links between diabetes and cancer; the potential biological mechanisms linking diabetes, obesity and cancer; the risk of cancer associated with antidiabetic medications.

Methods The data discussed in this review were obtained from the American Association of Clinical Endocrinologists Consensus Conference on Diabetes and Cancer, held in New York, NY, USA, September 2012.

Results The results of these studies demonstrate a significant association between diabetes and the risk of multiple cancers, including hepatocellular, pancreatic, endometrial, colorectal, breast, kidney, bladder, gastric, and ovarian cancer, non-Hodgkin lymphoma, T cell lymphoma and leukemia. There are multiple potential biological mechanisms that may link type 2 diabetes, obesity and cancer. Insulin resistance and hyperinsulinemia may lead to direct activation of the insulin receptors on tumor cells and promote tumor growth. Other potential mechanisms include increased circulating, local or bioavailable insulin-like growth factor 1, hyperglycemia, dyslipidemia, increased circulating or local estrogen, adipokines and direct and indirect effects of inflammatory cytokines. Epidemiological studies have had conflicting results regarding the associations between various classes of antidiabetic medication and cancer development. Animal studies have demonstrated increased tumor growth with certain medications, but their relevance to humans is uncertain. Metformin may, however, have protective effects on cancer development and may improve survival in patients with cancer.

Conclusion We describe the current understanding of the links among diabetes, antidiabetic medication and cancer risk. We highlight some of the issues that should be addressed in the future to prevent cancer development and death in those with diabetes.

Department of Medicine, Division of Endocrinology, Mt Sinai School of Medicine, New York, New York, USA

Correspondence to Derek LeRoith, MD, PhD, FACP, Division of Endocrinology, Diabetes & Bone Disease, Department of Medicine, Mt Sinai School of Medicine, One Gustave L. Levy Place, Atran 4th floor-36, Box 1055 New York, NY 10029-6574, USA. Tel: +1 212 241 6306; fax: +1 212 241 4159; e-mail:

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins