Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients: A systematic review and meta-analysis

Background:Recent clinical trials indicated that metformin intake might play a protective role in the incidence and oncologic outcomes of various cancers. However, its protective effect on bladder cancer remains uncertain.Methods:We performed a meta-analysis to investigate the association between metformin intake and bladder cancer risk as well as oncologic outcomes in diabetes mellitus (DM) patients. A comprehensive literature search was performed using PubMed, Embase, and the Cochrane Central Search Library in December 2017. Hazard ratio (HR) with 95% confidence interval (CI) was pooled.Results:A total of 9 retrospective cohort studies with 1,270,179 patients were included. A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR=0.55, 95% confidence interval [CI]=0.35-0.88; P=.01; I-2=64%), improved progression-free survival (HR=0.70, 95% CI=0.51-0.96; P=.03; I-2=33%), and prolonged cancer-specific survival (HR=0.57, 95% CI=0.40-0.81; P=.002; I-2=0%). However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HR=0.82, 95% CI=0.61-1.09; P=.17; I-2=85%) or an increased overall survival in bladder cancer patients (HR=0.83, 95% CI=0.47-1.44; P=.50; I-2=64%).Conclusion:The present meta-analysis indicated that metformin intake could improve the prognosis of bladder cancer patients. Further prospective cohort studies and mechanistic studies are still required to determine the precise role of metformin in the initiation and progression of bladder cancer.