Efficacy of three modern anti-diabetic drugs on survival outcomes of lung cancer patients with type 2 diabetes in China

Background Some anti-diabetic drugs have been proved to be a tumor suppressor or activator. The associations 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 The electronic medical data from the National Healthcare Big Data (East) Center was retrospectively analyzed. We included 11,357 newly diagnosed lung cancer patient with type 2 diabetes (T2D) between January 1st, 2020 and July 1st, 2023. Patients were categorized into eight groups according to the mono-or-combination therapy of GLP-1RA, DPP-4I and SGLT-2I. Disease progression and mortality risk were evaluated by cox proportional hazards analysis. Progression-free survival (PFS) and overall survival (OS) were assessed by the Kaplan-Meier (log-rank) method.Results Lung cancer patients with T2D who were treated with SGLT-2I & GLP-1RA exhibited the lowest progression (hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.18, 0.78) and mortality risks (HR: 0.34; 95% CI: 0.14, 0.82) as well as prolonged median PFS (1.55 years) and OS (1.62 years) among all groups. In contrast, DPP-4I monotherapy did not show benefit for progression (HR: 1.09; 95% CI: 0.98, 1.22. Median PFS: 1.41 years) and mortality risks (HR: 0.96, 95%CI: 0.84, 1.09. Median OS: 1.48 years). However, when DPP-4I was used in combination with SGLT-2I or GLP-1RA, it caused reductions in both progression and mortality risks.Conclusion SGLT-2I & GLP-1RA dual therapy is associated with improved prognosis for lung cancer patients with concurrent T2D. DPP-4I transits from a tumor activator to suppressor when combined with other anti-diabetic drugs. Future studies are needed to examine the underlying biological mechanisms.