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Objective:  Resistance to anticancer agents ensures a poor prognosis in patients with lung cancer. Metformin could enhance the anticancer effects of standard antineoplastic agents [traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)]; however, it is unclear whether metformin can be combined with antineoplastic agents in the treatment of lung cancer. To explore the efficacy of combinational strategies, we performed a systematic review and meta-analysis for diabetic and non-diabetic patients with lung cancer.    Method:  An electronic literature search was performed to obtain relevant randomized controlled trials (RCTs) and observational cohort studies. Hazard ratios (HR) with 95% confidence intervals (CI) of overall survival (OS) and progression-free survival (PFS) outcomes were extracted. Subgroup analysis by antineoplastic agents, study type, histology and clinical stage were investigated.    Results:  14 studies (three RCTs and eleven observational cohort studies) consisting 3,856 patients were included in the meta-analysis. Compared to standard antineoplastic agents alone (traditional chemotherapy drugs, EGFR-TKIs or ICIs), the antineoplastic agents combined with metformin significantly improved OS (HR 0.73, 95% CI 0.66–0.81,  p  < 0.00001) and PFS (HR 0.72, 95% CI 0.59–0.88,  p  = 0.001); a similar association was found in observational evidence. Limited data from RCTs showed no differences in OS or PFS.    Conclusion:  Metformin plus antineoplastic agents may improve survival outcomes of patients with lung cancer. Further investigation is needed.

frontiers in pharmacology

Metformin Adjunct With Antineoplastic Agents for the Treatment of Lung Cancer: A Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies