Clinical Effect of Treatment with Metformin for Type 2 Diabetes on Non-Small Cell Lung Cancer Patients Undergoing Immunotherapy: A Retrospective Study

To further identify the clinical impact of metformin on the prognosis of non-small cell lung cancer (NSCLC) with type 2 diabetes who received immunotherapy. Stage IV NSCLC patients with type 2 diabetes receiving the immunotherapy from 2017 to 2021 were retrospectively enrolled and divided into the metformin group or non-metformin group according to the treatment strategy for type 2 diabetes (metformin vs other hypoglycemic medicines). The overall response rate (ORR) was primary endpoint, and overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) were secondary endpoints. These outcomes were compared between two groups. A total of 34 patients were eventually enrolled, including 18 patients in the metformin group. No significant differences in the basic characteristics and incidence of adverse events were observed between two groups. In addition, there was no significant difference in ORR (44.4%, 8/18 vs 25.0%, 4/16, P = 0.236) and DCR (77.8%, 14/18 vs 75.0%, 12/16, P > 0.999) between the metformin and non-metformin groups. Kaplan-Meier survival curve (P = 0.039) and Cox regression analysis indicated that the use of metformin was an independent factor for OS (HR: 0.310, 95% CI: 0.113-0.845, P = 0.022), but not for PFS (Cox regression analysis: P = 0.145). For NSCLC patients with type 2 diabetes, the combination of metformin and immunotherapy may contribute to OS benefits. However, more high-quality prospective studies with big sample sizes are needed to further clarify the effect of metformin use on the efficacy of immunotherapy in advanced NSCLC patients with diabetes.