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#Diabetes and Endocrinology
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.
- 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.