Dissecting the role of metformin in urogenital malignancies

Metformin has shown great potential for anti-tumor therapy according to laboratory results, but there is currently no consensus on the role it playing in the pathogenesis of urogenital malignancies. Initially, a systematic review was conducted on clinical research examining the association between the use of metformin and the incidence and prognosis of prevalent urogenital malignancies. Then, a retrospective analysis of the participants in NHANES was performed to strengthen the study. Given the distinct methodological advantages of Mendelian randomization (MR) in research design, whereby genetic variations influencing the exposure of interest are independent of potential confounders, available GWAS data were thoroughly collected and utilized in a two-sample MR analysis to assess the causal relationships between metformin use and various urogenital malignancies. The review of literature demonstrated inconsistencies and ambiguities in clinical findings. The retrospective analysis of 20,527 participants in the NHANES did not reveal strong evidence in the four urogenital malignancies. The current MR study indicates that metformin use is unlikely to be a causal factor in the development of five urogenital malignancies (P > 0.05), either does the reverse MR analysis (P > 0.05). Nevertheless, the results were reliable to some extent since neither heterogeneity nor pleiotropy was detected in most cases. This study suggests that metformin use does not demonstrate a protective effect on the studied urogenital malignancies, contradicting the positive results observed in laboratory settings. Additional evidence from clinical studies is required to validate this conclusion.