Metformin Use and Mortality in Women with Ovarian Cancer: An Updated Meta-Analysis

BACKGROUND: Previous observational studies and meta-analysis suggested a possible association between metformin use and reduced mortality in women with ovarian cancer (OC). However, clinical factors that may influence the relationship remain poorly evaluated. We performed an updated meta-analysis to systematically evaluate the above association and to observe the potential influences of study characteristics on the association. METHODS: Relevant studies reporting the association between metformin use and mortality in women with OC in the multivariate adjusted model were identified by search of electronic databases that included PubMed, Embase, and Web of Science. The random-effects model was adopted to combine the results. RESULTS: Nine studies including 10030 women with OC were included. Overall, metformin use was independently associated with reduced overall mortality (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55–0.93, P=0.01; I(2) = 62%). Consistent results were observed for studies comparing metformin users with nondiabetic women and studies comparing metformin users with diabetic women who did not use metformin (P for subgroup analysis = 0.70). Further subgroup analyses showed consistent results in studies with metformin use before or after the diagnosis of OC, with or without adjustment of body mass index (BMI) and with or without adjustment of concurrent medications (P for subgroup analyses all >0.10). CONCLUSION: Metformin use is associated with reduced mortality in women with OC, which may be independent of the diabetic status of the controls, timing of metformin use, or adjustment of BMI and concurrent medications. Clinical trials are needed to validate the potential benefits of metformin on survival of OC.