Abstract
BACKGROUND: Some antidiabetic drugs have been shown to have tumor suppressor or activator properties. The associations between the treatment durations of three relatively new classes of antidiabetic medications, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP-4I), and sodium-glucose cotransporter 2 inhibitors (SGLT-2I), and lung cancer prognosis remain unclear. METHODS: A retrospective analysis was conducted on 11,357 newly diagnosed lung cancer patients with type 2 diabetes; these patients were recruited from the National Healthcare Big Data (East) Center and were divided into three groups based on their use of DPP-4I, GLP-1RA, or SGLT-2I, along with categorization of their treatment durations. Cox proportional hazards models were employed to assess the associations between drug duration and survival outcomes, including progression-free survival (PFS) and overall survival (OS). The multivariable models were adjusted for covariates like age, sex, smoking status, biomarkers, and cancer treatments. Sensitivity analyses and Kaplan-Meier estimates were used to validate the findings. RESULTS: In terms of the PFS, the highest quartile of GLP-1RA treatment (≥560 days) showed a lower incidence of cancer progression (hazard ratio (HR): 0.43; 95% confidence interval (CI): 0.18, 1.03), although the results were not statistically significant. DPP-4I and SGLT-2I showed less consistent trends. In terms of OS, GLP-1RA demonstrated a linear dose-response characteristic with reduced mortality risk over longer treatment durations, whereas DPP-4I and SGLT-2I showed non-linear associations. The sensitivity analyses confirmed these findings. CONCLUSION: Longer treatment durations of GLP-1RA, SGLT-2I, and DPP-4I reduced the risks of disease progression and mortality in lung cancer patients with type 2 diabetes. Among these drug classes, GLP-1RA showed consistent benefits while DPP-4I and SGLT-2I had non-linear associations, with shorter treatment durations being linked to higher risk.