Abstract
Background and purpose: Previous studies have found that metformin can inhibit tumor growth and improve outcomes for cancer patients. However, the association between the addition of metformin to the treatment regimen and survival in non-small cell lung cancer (NSCLC) patients receiving antineoplastic agents such as chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and immune checkpoint inhibitors (ICIs) remains unclear. This study aimed to evaluate the effect of metformin in NSCLC patients who received the aforementioned antineoplastic therapies. Methods: Several electronic databases were searched for relevant studies published by 10 September 2022. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS); eligible studies were those comparing patients with and without the addition of metformin. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined, with all statistical analyses performed using STATA 15.0. Results: A total of 19 studies involving 6,419 participants were included, of which six were randomized controlled trials. The overall pooled results indicate that the addition of metformin improved OS (HR = 0.84, 95% CI: 0.71-0.98, p = 0.029) and PFS (HR = 0.85, 95% CI: 0.74-0.99, p = 0.039). However, subgroup analysis based on treatment type and comorbidity of diabetes mellitus demonstrated that improvements in OS and PFS were observed only in diabetic and EGFR-TKI-treated patients (OS: HR = 0.64, 95% CI: 0.45-0.90, p = 0.011; PFS: HR = 0.59, 95% CI: 0.34-1.03, p = 0.061). Conclusion: Overall, this meta-analysis found that metformin use could improve outcomes for diabetic patients receiving EGFR-TKIs. However, no significant association between the addition of metformin and the survival of non-diabetic NSCLC patients receiving chemotherapy or ICI therapy was identified based on the current evidence.