Abstract
BackgroundMetformin 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.ResultsA 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).MethodsRelevant 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.ConclusionsOur 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.
Highlights
Biguanides, commonly known as metformin, are one type of the most widely prescribed drugs mainly to lower blood glucose for patients with type 2 diabetes
A total of 561 citations were identified for eligibility through the systematic literature search
Five studies investigated the association between metformin use and recurrence-free survival (RFS), we found that metformin use was significant associated with improved RFS for prostate cancer (PCa) Patients (n = 5, hazard ratios (HRs) 0.74, 95% CI 0.58–0.95)
Summary
Biguanides, commonly known as metformin, are one type of the most widely prescribed drugs mainly to lower blood glucose for patients with type 2 diabetes. Experimental studies have shown that metformin has antineoplastic effects in several malignant tumors, including breast cancer, pancreatic cancer, and prostate cancer (PCa) [1,2,3]. In breast cancer xenograft models, metformin has been shown to enhance the effect of chemotherpy and prolong remission in breast cance cell line. In colon cancer cell lines, metformin www.impactjournals.com/oncotarget can enhance the chemosensitivity of 5-fluorouracil and oxaliplatin [5, 6]. Metformin has been shown to improve survival in diabetic patients with advanced endometrial cancer and non-small cell lung cancer [7, 8]. Metformin has been implicated to reduce the risk of prostate cancer (PCa) beyond its glucose-lowering effect. The influence of metformin on prognosis of PCa is often controversial
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