Metformin has no Significant Anticancer Effect on Patients with Advanced or Unresectable Cancer: A Systematic Review and Meta-analysis

Abstract

Background: At present, the antitumor effect of metformin is controversial. Previous meta-analyses included observational studies, of which the results can be influenced by many confounders, affecting the result of meta-analyses and weakening the strength of evidence. Therefore, we conducted a meta-analysis to confirm the effect of metformin use on patients with advanced or unresectable cancers, including randomized clinical trials (RCTs). Methods: We searched for RCTs in accordance with the inclusion and exclusion criteria. A meta-analysis was conducted to combine hazard ratios (HRs) or risk ratios (RRs) and their 95% confidence intervals (CIs) using a random-effects model. Results: Finally, 7 eligible RCTs were included in the meta-analysis. Overall, the combined results revealed that treatment with metformin did not improve the overall survival (OS) of patients (HR, 1.12; 95% CI, 0.91-1.37, p>0.05), and there was no clear evidence that metformin use was related to improved progression-free survival (PFS) (HR, 1.17; 95% CI, 0.97-1.40; p>0.05). The pooled RR for grade III or IV adverse events was 0.92 (95% CI, 0.52- 1.60; p>0.05), indicating that the use of metformin was not significantly related to increased toxicity. Conclusion: Metformin does not significantly improve the survival of patients with advanced or unresectable cancer, regardless of cancer type and region. Open Science Framework: DOI 10.17605/OSF.IO/SPKE8.