ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
This article is part of the Research TopicMechanisms Linking Cancer and Metabolic Diseases: From Molecular Pathways to Therapeutic InterventionsView all articles
Effect of treatment duration on the association between three modern anti-diabetic drugs and survival outcomes of lung cancer in China
Provisionally accepted
- 1China Academy of Chinese Medical Sciences, Beijing, China
- 2Hengshui Traditional Chinese Medicine Hospital, Hengshui, China
- 3Guangzhou University of Chinese Medicine, Guangzhou, China
- 4China Academy of Chinese Medical Sciences Guang'anmen Hospital, Beijing, China
- 5People's Liberation Army Air Force Special Medical Center, Beijing, China
- 6China Academy of Chinese Medical Sciences Xiyuan Hospital, Beijing, China
- 7The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Background: Some anti-diabetic drugs have been proved to be a tumor suppressor or activator. The associations of the treatment duration of three relatively new classes of anti-diabetic medications–glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP-4I), and sodium-glucose cotransporter 2 inhibitors (SGLT-2I) with lung cancer prognosis remain unclear. Methods: A retrospective analysis was conducted on 11,357 newly diagnosed lung cancer patients with type 2 diabetes from the National Healthcare Big Data (East) Center. Patients were divided into three groups based on their use of DPP-4I, GLP-1RA, or SGLT-2I, with treatment duration categorized. Cox proportional hazards models were employed to assess associations between drug duration and survival outcomes, including progression-free survival (PFS) and overall survival (OS). Multivariable models adjusted for covariates like age, sex, smoking, biomarkers, and cancer treatments. Sensitivity analyses and Kaplan-Meier estimates were used to validate findings. Results: In terms of PFS, the highest quartile of GLP-1RA treatment (≥560 days) had a lower incidence of cancer progression (HR: 0.43, 95% CI: 0.18, 1.03), although results were not statistically significant. DPP-4I and SGLT-2I showed less consistent trends. For OS, GLP-1RA demonstrated a linear dose-response, reducing mortality risk with longer treatment duration, while DPP-4I and SGLT-2I showed non-linear associations. Sensitivity analyses confirmed these findings. Conclusion: Longer treatment durations of GLP-1RA, SGLT-2I, and DPP-4I reduced risks of disease progression and mortality in lung cancer patients with type 2 diabetes. GLP-1RA showed consistent benefits, while DPP-4I and SGLT-2I had non-linear associations, with shorter treatment durations linked to increased risks.
Keywords: ankylosing spondylitis, Diabetes Mellitus, Glucolipid metabolism, Inflammation, immune
Received: 08 Sep 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Chen, Wang, Zhang, Yang, Lei, Di, Huang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ye Huang
Yan Li
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