The addition of metformin to systemic anticancer therapy in advanced or metastatic cancers: a meta-analysis of randomized controlled trials

Preclinical studies have demonstrated that metformin has anticancer properties and act in additive or synergistic way when combined with anticancer agents. We conducted this meta-analysis of randomized clinical trials to evaluate the effect of metformin added to systemic anticancer therapy in patients with advanced or metastatic cancer. A computerized systematic electronic search was performed using PubMed, PMC, EMBASE, Cochrane Library, and Web of Science databases (up to June 2020). From nine randomized clinical trials, 821 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for overall response rate (ORR) and hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). The concomitant use of metformin with systemic anticancer therapy did not increase tumor response (the pooled OR of ORR = 1.23, 95% CI: 0.89-1.71, p = 0.21), compared with anticancer therapy alone. In terms of survival, metformin added to anticancer agents failed to prolong PFS (HR = 0.95, 95% CI: 0.75-1.21, p = 0.68) and OS (HR = 0.97, 95% CI: 0.80-1.16, p = 0.71). In conclusion, this meta-analysis of randomized clinical trials indicates that the addition of metformin to systemic anticancer therapy has no clinical benefits in patients with advanced or metastatic cancer.