The effect of metformin administration on cancer-specific survival, overall survival, progression-free survival, and disease progression in renal cell carcinoma patients; a systematic review and meta-analysis

Introduction: The increase in the incidence of renal cell carcinoma (RCC) has been reported worldwide. The anti-cancer impacts of metformin on the various types of cancer have been observed in clinical studies. Therefore, this study aims to survey the effect of metformin use on RCC patients using systematic review and meta-analysis methods. Materials and Methods: In this research, Cochrane, Web of Science, PubMed, Scopus databases, and Google Scholar web browser were searched using standard keywords. Data were analyzed with STATA 14 software. The significance level of tests P<0.05 was considered. Results: The improvement in the progression-free survival (PFS) (HR: 0.72 (95% CI: 0.54, 0.94), P=0.169, I2=37.8%) and cancer-specific survival (CSS) (HR: 0.36 (95% CI: 0.18, 0.75), P=0.339, I2=7.5%) was observed in eight studies with 10404 patients affected by RCC. However, no significant statistical effect was observed on the improvement in the disease progression (OR: 1.10 (95% CI: 0.85, 1.42), P=0.326, I2=0%) and cancer overall survival (OS) (HR: 0.72 (95% CI: 0.51, 1.01), P=0.153, I2=43.1%). Conclusion: This study showed metformin administration improved CSS and PFS in RCC patients. More studies are warranted on the effect of metformin on the improvement in disease progression and OS of cancer. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID= CRD42022369108; https://www.crd.york. ac.uk/prospero/display_record.php?ID=CRD42022369108).