Combined regimens of cisplatin and metformin in cancer therapy: A systematic review and meta-analysis

Cancer cell resistance to chemotherapy agents is a challenging issue in treating patients with cancer. Findings suggest that a combination of drugs may have synergistic or additive effects. in the present study, we systematically reviewed the combined regimens of metformin with cisplatin in various treating cancers.A comprehensive systematic search was performed in PubMed, Scopus, Embase, and other relevant databases with the following keyword "metformin", "cisplatin", "combination", "using all their equivalents and similar terms. Pooled odds ratio (OR) and 95% confidence intervals of cell viability and tumor volume as primary outcomes were calculated using Der-Simonian and Laird method while random effects meta-analysis was used, taking into account clinical and statistical heterogeneity.Overall, 44 studies were retrieved, Findings of the present meta-analysis showed that combined regimens of metformin plus cisplatin was significantly associated with decreased odds of tumor volume and cell viability for all cancers compared with cisplatin alone (pooled OR: 0.40; 95% CI: 0.27, 0.58) and (pooled OR: 0.49; 95% CI: 0.42, 0.58) respectively. The result was same for cell viability in lung cancer (pooled OR: 0.59; 95% CI: 0.49, 0.70). The tumor size reduction and the response rate were evident in the animal xenografts model.Findings indicated that combining metformin with cisplatin is a practical therapeutic approach to increase treatment efficacy in the case of cell viability and tumor volume and minimize side effects. A combination of metformin with cisplatin could enhance treatment efficacy through synergistic inhibitory effects on the growth of cancer cells.