Use of metformin has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates. Various factors make metformin an appealing option for repurposing as an anti-cancer therapy. It has been administered along with most cancer treatments without any important interactions. The anti-cancer properties of this drug have been proposed to result from both direct effects on cancer cells, especially through inhibition of the AMPK/mTOR pathway, and indirect effects on the host, by virtue of its blood glucose-lowering properties and anti-inflammatory actions. Both mechanisms are of paramount importance, however, their relative contribution may differ according to the stage of disease. Studies in the past have revealedan anti-proliferative effect in breast cancer and a reduction in precancerous changes in the colorectum. A randomised phase III trial of non-diabetes mellitus patients reported that when compared to placebo, low-dose metformin was effective in the chemoprevention of metachronous colorectal adenomas or polyps. The researchers have also performed a meta-analysis to quantify the adjuvant effect of metformin on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS).Of 7,670 articles screened, 27 eligible studies were identified comprising 24,178 participants, all enrolled in observational studies. In patients with early-stage colorectal cancer, metformin use resulted in a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47-0.85; OS HR 0.69, CI 0.58-0.83; CSS HR 0.58, CI 0.39-0.86]. For males with early-stage prostate cancer, metformin was associated with significant, or borderline significant benefits in all outcomes (RFS HR 0.83, CI 0.69-1.00; OS HR 0.82, CI 0.73-0.93; CSS HR 0.58, CI 0.37-0.93). The findings suggested that metformin could be a valuable adjuvant drug, with the greatest benefits in patients with colorectal and prostate cancer, especially in those receiving radical radiotherapy.

Reference

1. Coyle C, Cafferty FH, Vale C,et al. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann Oncol. 2016 Dec;27(12):2184-2195.