OBJECTIVES: Metformin has anticancer properties and has been associated with decreased incidence and improved survival among patients with several cancers. Inconsistent evidence exists regarding the beneficial effects of metformin in women with ovarian cancer. We updated the evidence by performing a systematic review and meta-analysis to examine the effect of metformin on all-cause mortality among ovarian cancer patients with comorbid diabetes.

METHODS: Original articles published in English until December 2018 were searched in Medline-Ovid, PubMed, The Cochrane Library, and also searched the conference abstracts presented at the conferences at the International Society for Pharmacoeconomics and Outcomes Research, National Comprehensive Cancer Network and American Society of Clinical Oncology, for studies on metformin use in ovarian cancer with comorbid diabetes. Meta-analysis was performed using RevMan to determine the pooled hazard ratio (pHR) and its 95% confidence interval (CI). I² statistics was examined to evaluate heterogeneity between the studies. Study quality assessment was conducted using the Cochrane Risk of Bias tool for the randomized controlled trial (RCT) and Newcastle-Ottawa Quality Assessment Scale for cohort studies.

RESULTS: Four studies, one RCT and three retrospective cohort studies, met the inclusion criteria and were included in the meta-analysis. Compared to women who had no metformin use, those who used metformin had lower all-cause mortality, however the association was not significant (pHR=0.47, 95% CI=0.21-1.09, p=0.08, I²=79%). A subgroup analysis of retrospective cohort studies also did not change the findings.

CONCLUSIONS: Metformin has a marginal yet nonsignificant beneficial effect on overall survival in women with ovarian cancer with comorbid diabetes. Due to the possible selection bias in the observational studies, RCTs should be designed to evaluate the efficacy of metformin use in ovarian cancer.