CONTEXT: The association between colorectal cancer (CRC) and new-onset diabetes mellitus remains unclear. OBJECTIVE: To examine the association between CRC and the risk of subsequent diabetes mellitus and to further investigate the impact of chemotherapy on diabetes mellitus risk in CRC. METHODS: In this nationwide cohort study using the Taiwan Cancer Registry database (2007-2018) linked with health databases, 86 268 patients with CRC and an equal propensity score-matched cohort from the general population were enrolled. Among them, 37 277 CRC patients from the Taiwan Cancer Registry (2007-2016) were analyzed for diabetes mellitus risk associated with chemotherapy. Chemotherapy exposure within 3 years of diagnosis was categorized as no chemotherapy, <
90 days, 90 to 180 days, and >
180 days. Differences in diabetes mellitus risk were assessed across these categories. RESULTS: Each group involved 86 268 participants after propensity score matching. The patients with CRC had a 14% higher risk of developing diabetes mellitus than the matched general population (hazard ratio [HR]: 1.14
95% CI, 1.09-1.20). The highest risk was observed within the first year after diagnosis, followed by a sustained elevated risk. Long-term chemotherapy (>
180 days within 3 years) was associated with a 60% to 70% increased risk of subsequent diabetes mellitus (HR: 1.64
95% CI, 1.07-2.49). CONCLUSION: Patients with CRC are associated with an elevated risk of diabetes mellitus, and long-term chemotherapy, particularly involving capecitabine, increases diabetes mellitus risk. Thus, monitoring blood glucose levels is crucial for patients with CRC, especially during extended chemotherapy.