Association of co-administration of neurokinin-1 receptor antagonists and dexamethasone with new-onset diabetes in patients receiving chemotherapy: a retrospective cross-sectional study using health claims database in Japan

Purpose We aimed to optimize antiemetic strategies by evaluating the association of co-administration of neurokinin-1 receptor antagonist (NK1-RA) administration and dexamethasone on new-onset diabetes in patients receiving chemotherapy. Methods This retrospective cross-sectional study was conducted using the DeSC database and included patients aged ≥ 18 years with solid tumors who initiated parenteral anticancer agents and dexamethasone between April 2014 and March 2023. Patients with a history of diabetes or hematologic malignancies were excluded. The primary outcome was new-onset diabetes during the 2 months following the index month, defined by International Classification of Diseases, Tenth Revision codes or prescription data. Multivariable logistic regression assessed the association between co-administration of NK1-RA and dexamethasone and new-onset diabetes. Results Among 71,539 eligible patients, 51.1% received NK1-RAs. Co-administration of NK1-RA and dexamethasone was significantly associated with an increased risk of new-onset diabetes (adjusted odds ratio: 1.43; 95% confidence interval: 1.31–1.55; p < 0.001). Sensitivity analyses demonstrated consistent results across different evaluation periods and outcome definitions. Conclusion Co-administration of NK1-RA and dexamethasone was associated with an increased risk of new-onset diabetes. These findings highlight a previously unrecognized safety signal and support the careful management of dexamethasone, as recommended by many clinical guidelines.