Metformin is associated with survival benefit in cancer patients with concurrent type 2 diabetes: a systematic review and meta-analysis

Abstract

Patients with type 2 diabetes have increased cancer risk and cancer-related mortality, which can be reduced by metformin treatment. However, it is unclear whether metformin can also modulate clinical outcomes in patients with cancer and concurrent type 2 diabetes.

Patients and methods: A meta-analysis of 20 publications that included 13,008 subjects was performed to investigate the association between metformin and overall survival (OS) as well as cancer-specific survival (CSS) in patients with cancer and concurrent type 2 diabetes.

Results: We found that there was a relative survival benefit associated with metformin treatment compared with treatment with other glucose-lowering medications in both OS and CSS (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.55-0.79 and HR = 0.62; 95% CI: 0.46-0.84, respectively). These associations were also observed in subgroups by cancer type and country.

Conclusion: These results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes.

Keywords: Cancer; Diabetes; Meta-Analysis; Metformin; Survival.

Figure 1.

Study flow chart for the process of selecting the final 20 publications. Abbreviations: OS, overall survival.

Figure 2.

Hazard ratios (HRs) of overall survival by metformin versus non-metformin exposure. For each study, the estimates of HR and 95% CI were plotted with a box and a horizontal line. Closed diamond indicates pooled HR and 95% CI. Abbreviations: CI, confidence interval; df, degrees of freedom.

Figure 3.

Funnel plot analysis to detect publication bias. Each circle represents an individual study for the indicated association. Hollow circles indicate original observation studies; solid circles indicate missing studies by trim and fill method. Abbreviation: s.e., standard error.