2021 - The Addition of Metformin to Systemic Anticancer Therapy

Background

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, controlled trials to evaluate the effect of metformin added to systemic anticancer therapy in patients with advanced or metastatic cancer.

Methods

A computerized systematic electronic search was performed using PubMed, PMC, EMBASE, Cochrane Library, and Web of Science databases (up to March 2019). From six randomized, controlled trials, 418 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).

Results

The studies enrolled patients with advanced or metastatic pancreatic cancer (PC), non-bmall-cell lung cancer (NSCLC), and breast cancer (BC). The dose of metformin used was from 500 mg/d to 2 g/d. Jadad score was more than 3 in all the studies, indicating a good quality of each study.The combination of metformin with anticancer therapy did not improve tumor response (the pooled OR of ORR = 1.20, 95% CI: 0.72-1.99, p = 0.48), compared with anticancer therapy alone. In terms of survival, metformin added to anticancer agents failed to prolong PFS (HR = 0.98, 95% CI: 0.71-1.35, p = 0.90) and OS (HR = 0.95, 95% CI: 0.75-1.21, p = 0.67).

Conclusions

In conclusion, this meta-analysis of randomized, controlled phase II trials do not support clinical benefits of metformin added to systemic anticancer therapy in patients with advanced or metastatic cancer. However, further investigations including well-designed phase III trials are needed to resolve the issues (dose of metformin, treatment setting, particular cancer type, or immunomodulatory effect) on the addition of metformin to systemic anticancer therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Jung Han Kim.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.