Safety of Short-T erm Low-Dose Olanzapine in Patients with Cancer and Diabetes Receiving Cisplatin-Based Chemotherapy: A Retrospective TriNetX Cohort Study.

Purpose: Quadruple antiemetic prophylaxis with olanzapine (OLZ) is internationally recommended for cisplatin-based chemotherapy. However, OLZ is contraindicated by country-specific regulatory labeling in patients with diabetes mellitus (DM) in Japan due to concerns regarding hyperglycemia. This study aimed to evaluate the safety of short-term low-dose OLZ (≤10 mg) in patients with cancer and DM. Patients and Methods: We conducted a retrospective cohort study using the TriNetX multi-institutional electronic medical records network. Patients aged ≥18 years who received cisplatin were included in the study. The primary outcome was the incidence of DM-related adverse events (hyperosmolar hyperglycemic state or diabetic ketoacidosis) within 30 days. Secondary outcomes included glucose elevation, neuropsychiatric events, and acute inpatient visits. Propensity score matching was used to balance the baseline covariates. Results: In the matched cohorts (n = 84 per group), no DM-related adverse events occurred within 30 days in either group; however, the occurrence of zero events limited definitive comparative inferences. Although patients with DM had higher glucose levels than those without DM at multiple time points, these increases remained modest (mean, approximately 150 mg/dL). No acute inpatient visits or neuropsychiatric events were reported. Sensitivity analyses stratified by the timing and frequency of OLZ exposure confirmed these findings across various exposure patterns. Conclusion: Based on the absence of detected events rather than demonstrated equivalence, short-term low-dose OLZ administration was not associated with detectable severe glycemic complications in this real-world cohort, supporting prospective evaluation and individualized monitored use in selected patients.