The Survival Effect of Metformin on Non-Small Cell Lung Cancer Treated with Chemotherapy: A Systematic Review

Objective. Metformin is a common antidiabetic drug that has been reported to serve as an anticancer agent in combination with other therapies. But the effect of the addition of metformin on the survival of non-small cell lung cancer (NSCLC) patients undergoing chemotherapy is still controversial. We conducted this systematic review to evaluate the survival effect of metformin added to chemotherapy in NSCLC patients. Methods. Electronic literature search was performed in the PubMed, Embase, and Web of Science databases from their inception up to April 2023. The study region, study design, histological subtype of the NSCLC, tumor stage, treatment strategy, sample size, follow-up duration, diabetes status, and HR of OS or PFS of the included studies were extracted. The quality was assessed through Cochrane collaboration’s tool for RCT and the Newcastle–Ottawa scale (NOS) for observational studies, respectively. Results and conclusions. Eleven studies with a total of 4606 patients were finally included. Five RCTs showed a high risk of bias due to the open-label nature while six retrospective studies were of high quality. Two studies of NSCLC patients with diabetes reported significant benefits in overall survival from metformin addition, while one study of patients without diabetes reported a negative effect on the survival of metformin addition. The survival impact of metformin added to chemotherapy on unresectable NSCLC patients remains inconclusive. The survival benefit might be more prominent in patients with diabetes, awaiting further evidence.