The Relationship between Metformin Consumption and Cancer Risk: An Updated Umbrella Review of Systematic Reviews and Meta-Analyses.

Background: Considering that metformin is widely used in the treatment of diabetes, and its protective role against various malignancies, the strength and validity of the available evidence from related systematic reviews and meta-analysis were evaluated. Methods: Scopus, PubMed, Embase, Cochrane, Web of science databases, and Google Scholar and manual screening of retrieved references were systematically searched from their inception dates to 24 March 2020 by extracting the effect size (Odds ratios (OR) and relative risk (RR) in each study. To present the forest plot of effect of metformin on each cancer, Stata version 14.2 was used. Results: This study included 36 meta-analysis studies and 620 original research studies (26 randomized control trials studies and 594 observational studies (cohort, case-control)) covering 15 different cancers. Overall, metformin medication prevented different cancers, including ovarian cancer (OR = 0.76, 95% CI: 0.62,0.93), cervical cancer (OR = 0.60, 95% CI: 0.43, 0.83), endometrial cancer (OR = 1.05, 95% CI: 0.82,1.35), liver cancer (OR = 0.59, 95% CI: 0.47,0.74), pancreatic cancer (OR = 0.59, 95%CI 0.50,0.69), head and neck cancer (OR = 0.71, 95% CI: 0.61,0.83), stomach cancer (OR = 0.72, 95% CI: 0.26,1.99), colorectal cancer (OR = 0.73, 95% CI: 0.59,0.91), colorectal adenoma cancer (OR = 0.75, 95% CI: 0.65,0.86), colon cancer (OR = 0.79, 95% CI: 0.69,0.91), esophagus cancer (OR = 0.90, 95% CI: 0.83,0.98), lung cancer (OR = 0.92, CI95%:0.85,0.99), breast cancer (OR = 0.93, 95% CI: 0.84,1.02), prostate cancer (OR = 0.94, 95% CI: 0.85-1.04), and bladder cancer (OR = 0.94 95% CI: 0.64,1.38). Conclusions: Treatment with metformin can significantly decrease the chance of all cancers with larger preventive effect on hepatocellular carcinoma and smaller preventive effect on lung and breast cancers.