Dipeptidyl peptidase 4 inhibitors as novel agents in improving survival in diabetic patients with early stage non small cell lung cancer

<bold>Introduction:</bold> Prior studies have shown an anticancer effect of DPP4 inhibitors in patients with colorectal cancer. It is unclear, however, whether DPP4 inhitibors has a mortality benefit in lung cancer. <bold>Aims:</bold> To compare overall survival of patients with diabetes with early stage non–small cell lung cancer (NSCLC) taking DPP4 inhibitos versus those not on DPP4 inhibitors. <bold>Methods:</bold> Using data from The Chang Gung Research Database, we identified 258 patients with diabetes 65–80 years of age diagnosed with stage I-IIIA NSCLC between 2004 and 2020. We used propensity score methods to assess the association of DPP4 inhibitors use with overall survival while controlling for potential confounders. <bold>Main Results:</bold> Overall, 92 patients (36%) were on DPP4 inhibitors at the time of lung cancer diagnosis. Median survival in the DPP4 inhibitors group was 3.6 ±1.8 years, compared with 3.3 ±1.9 years in patients not treated with metformin (P < 0.005). Propensity score analyses showed that DPP4 inhibitors use was associated with a statistically significant improvement in overall survival (hazard ratio, 0.52; 95% confidence interval, 0.34–0.80), after controlling for sex, age, diabetes severity, lung cancer characteristics, and treatment. <bold>Conclusions:</bold> DPP4 inhibitors is associated with improved survival among patients with diabetes with early stage NSCLC, suggesting a potential anticancer effect. Further research should evaluate plausible biologic mechanisms and test the effect of metformin in prospective clinical trials.