Type II Diabetes, Metformin Use, and Colorectal Neoplasia: Mechanisms of Action and Implications for Future Research

Abstract

Type 2 diabetes mellitus has been associated with increased colorectal cancer incidence and mortality. Recently, metformin, a drug used widely for treatment of type 2 diabetes mellitus, has gained much attention because of its anticancer effect. Several observational and preclinical studies reported that metformin was associated with decreased risk of colorectal cancer and improved colorectal cancer survival. Although the exact mechanisms underlying the anticancer effect of metformin are not known, several mechanisms have been proposed, including AMP-activated protein kinase mediated inhibition of mammalian target of the rapamycin, decreasing insulin-like growth factor 1 levels, anti-inflammatory activity, cell cycle arrest, and cancer stem cell inhibition. In addition, in patients with colorectal cancer, metformin may have potential as a chemopreventive agent and adjuvant drug. Large-scale, well-designed, long-term, and randomized controlled trials are needed to confirm the potential benefit of metformin for both the diabetic population and the nondiabetic population.