OBJECTIVES: Type 2 diabetes mellitus (T2DM) patients have higher risk of developing various types of cancer including bladder cancer. Metformin is the first line agent used to treat T2DM. Evidence from the epidemiological studies found variable results for the association between metformin use and bladder cancer risk. So, this meta-analysis is aimed to confirm the association between metformin use and bladder cancer risk.

METHODS: PubMed and Embase databases were searched for the relevant article using suitable keywords. Literature search was performed by two independent reviewers. Quality of the included studies was determined using Newcastle-Ottawa scale. Incidence of bladder cancer among metformin user was the primary outcomes of interest. Subgroup and sensitivity analysis was also performed. Based on heterogeneity random or fixed effect model was chosen. All the analysis was performed using Review Manager version 5.3.

RESULTS: This meta-analysis was based on five articles including 1,269,642 patients of which 666,328 were on metformin and the remaining were non-metformin user. All the included studies were of high quality based on the score attainment on NOS scale. Pooled analysis revealed that metformin use was not associated with the bladder cancer risk with a relative risk (RR) of 0.82 [(95% CI: 0.61 to 1.09), p= 0.17, I²= 85%]. Random effect model was applied due to the presence of significant heterogeneity. Subgroup analysis based on geographical region revealed significant association between bladder cancer risk and metformin use in Asian patients RR 0.62 (95% CI:0.48 to 0.81), p <0.01.

CONCLUSIONS: We found no significant association between metformin use and urinary bladder cancer risk.