The impact of metformin use on survival in prostate cancer: a systematic review and meta-analysis

Background: Metformin has been implicated to reduce the risk of prostate cancer (PCa) beyond its glucose-lowering effect. However, the influence of metformin on prognosis of PCa is often controversial. Results: A total of 13 cohort studies encompassing 177,490 individuals were included in the meta-analysis. Data on overall survival (OS) and cancer-specific survival (CSS) was extracted from 8 and six studies, respectively. Comparing metformin users with non-metformin users, the pooled hazard ratios (HRs) for OS and CSS were 0.79 (95% confidence interval [CI] 0.63-0.98) and 0.76 (95% CI 0.57-1.02), respectively. Subgroup analyses stratified by baseline charcteristics indicated significant CSS benefits were noted in studies conducted in USA/Canada with prospective, large sample size, multiple-centered study design. Five studies reported the PCa prognosis for recurrence-free survival (RFS) and metformin use was significantly associated with patient RFS (HR 0.74, 95% CI, 0.58-0.95). Methods: Relevant studies were searched and identified using PubMed, Embase and Cochrane databases from inception through January 2017, which investigated associations between the use of metformin and PCa prognosis. Combined HRs with 95% CI were pooled using a random-effects model. The primary outcomes of interest were OS and CSS. Conclusions: Our findings provide indication that metformin therapy has a trend to improve survival for patients with PCa. Further prospective, multi-centered, large sample size cohort studies are warranted to determine the true relationship.