Effect of metformin on the prognosis of chemoradiotherapy cancer patients: a systematic review and meta-analysis of randomized controlled trials and cohort studies

Abstract

Abstract Background Metformin is a well-known drug used in the treatment of type-2 diabetes; nevertheless, the efficacy of metformin as an adjuvant in cancer therapy is still up for debate. We analyzed data from randomized trials and cohort studies to assess metformin's potential in chemoradiotherapy for cancer patients. Method A systematic search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted up to December 01, 2022; 16 randomized trials and 29 cohort studies were identified. The primary outcome was OS, followed by PFS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were created using random-effects meta-analysis models. Meta-regression and subgroup analysis were used to investigate heterogeneity. Publication bias assessment was performed. Result Metformin usage was mainly shown to be substantially linked to OS (HR = 0.88, 95% CI = 0.80–0.97). Subgroup analysis revealed that diabetic individuals on metformin had a substantially decreased risk of mortality when grouped by whether the study population was diabetic or not (HR = 0.62, 95% CI: 0.50–0.76). Patients receiving just chemotherapy had a longer OS when grouped by radiation status (HR = 0.75, 95% CI: 0.63–0.89). Further stratified analysis found that in the diabetic population, metformin improves prognosis in all cases (chemoradiotherapy, HR = 0.64, 95% CI: 0.46–0.88; radiotherapy alone, HR = 0.25, 95% CI: 0.09–0.71). Metformin, on the other hand, enhanced prognosis in patients receiving chemotherapy alone in conjunction with diabetes alone (diabetic, HR = 0.61, 95% CI: 0.48–0.77; non-diabetic, HR = 0.91, 95% CI: 0.65–1.27; partial diabetes, HR = 0.82, 95% CI: 0.68–0.99). Metformin usage and PFS were not significantly correlated in the total study (HR = 0.97, 95% CI = 0.81–1.16). Analyses of subgroups failed to reach statistical significance either. Only diabetes had a substantial impact on the combined OS result, according to heterogeneity tests, but the combined PFS outcome was unaffected. In the research, there was no discernible publication bias. Conclusion The results of our meta-analysis showed that metformin helped cancer patients with diabetes have a better prognosis, whether they got radiation, chemotherapy, or all three at the same time.