Metformin: current clinical applications in nondiabetic patients with cancer

Metformin is one of the most commonly used first-line oral medications for type 2 diabetes mellitus. Multiple observational studies, reviewed in numerous systematic reviews, have shown that metformin treatment may not only reduce the risk of cancer but may also improve the efficacy of cancer treatment in diabetic patients. Recent studies have been conducted to determine whether a similar protective effect can be demonstrated in nondiabetic cancer patients. However, the results are controversial. The potential optimal dose, schedule, and duration of metformin treatment and the heterogeneity of histological subtypes and genotypes among cancer patients might contribute to the different clinical benefits. In addition, as the immune property of metformin was investigated, further studies of the immunomodulatory effect of metformin on cancer cells should also be taken into account to optimize its clinical use. In this review, we present and discuss the latest findings regarding the anticancer potential of metformin in nondiabetic patients with cancer.