Background: Type 2 diabetes mellitus has been associated with an increased cancer risk, which can be modified by specific hypoglycemic drugs. In particular, metformin, the most frequently prescribed biguanide, is now considered a protective agent against cancer incidence and mortality in Type 2 diabetic patients.
Aims: To review the potential associations between metformin use and cancer incidence and mortality and the possible biological links implicated in these associations.
Materials and methods: We searched English-language original investigations published through September 2011.
Results: Metformin could block the mitogenic effects of insulin, but this effect does not entirely explain the reduction in cancer incidence. Metformin also plays a direct inhibition of cancer cell growth via the inhibitory effects of AMP-activated protein kinase on the mTOR pathway, which regulates cell growth and proliferation. Accordingly, many epidemiological studies have shown that metformin use is associated with a lower cancer incidence and mortality through a dose-response relationship, with greater exposure being associated with stronger risk reduction. Randomized clinical trials testing the effects of metformin on both recurrence and survival in early-stage breast cancer are on-going; these trials are based on pilot studies demonstrating an adjuvant effect of this drug in breast cancer.
Conclusions: Metformin is an inexpensive and safe drug, that may modify the increased cancer risk of Type 2 diabetic patients. On-going clinical trials will show whether this drug can enhance the effect of chemotherapy in the treatment of cancer.