Exploring the role of metformin in anticancer treatments: A systematic review

Abstract

Many clinical and preclinical studies suggest that metformin has antitumor activity. There are two main mechanisms that justify this effect: its ability to activate AMPK, preventing the gluconeogenesis in the liver and stimulating glucose uptake in muscle (insulin-independent), and its potential to negatively regulate mTOR activity (insulin- dependent). Thus, numerous studies have evaluated its role in cancer risk, prognosis and as an antitumor therapy in different malignancies. The following is a systematic review on the clinical evidence about the effects of metformin in cancer. Uncontrolled studies suggest that metformin is associated with reduced risk of different types of cancers among patients with hyperinsulinemia conditions, such as diabetes and obesity. However, among cancer patients, the literature is conflicting about the real impact of metformin on survival and outcomes of cancer treatments. The effects of metformin in nondiabetic patients remain unknown. Ongoing randomized trials are awaited to prove the true antineoplastic activity of metformin.