Immune Checkpoint Inhibitors-Associated Diabetes and Ketoacidosis Were Found in FDA Adverse Event Reporting System: A Real-World Evidence Database Study

Objective To investigate the risk of developing diabetes and ketoacidosis in clinical patients with Immune checkpoint inhibitors (ICIs). Methods We looked in the FDA Adverse Event Reporting System (FAERS) for reports of ICIs-associated DM and ketoacidosis between January 2004 and March 2022. We explored the signals using fourfold table-based proportional imbalance algorithms. Patient characteristics, country distribution, and outcomes of adverse reactions were described. Kruskal-Wallis test was used to compare the time of onset and prognosis of adverse reactions. Results A total of 2,110 reports of ICIs-related DM were included in the study. The largest number of reports was from Japan (752, 35.64%), followed by the United States and France (624, 29.57%; 183, 8.67%). Seven drugs detected signals of DM and ketoacidosis according to four proportional imbalance algorithms: Nivolumab, Pembrolizumab, Cemiplimab, Dostarlimab, Atezolizumab, Avelumab, and Durvalumab. Diabetes and ketoacidosis generally occured early in the course of ICIs treatment, the median time to event onset was 144.5 (interquartile range 27–199) days. ICIs-related diabetes and ketoacidosis events resulted in 934 major medical events (44.3%), 524 hospitalizations (24.8%), 60 life-threatening events (2.8%), 42 deaths (2.0%), and 39 disability events (1.8%). Conclusion The study reveals the risk and characteristics of diabetes and ketoacidosis associated with ICIs, which may provide evidence for post-marketing evaluation. Careful consideration should be given to the possibility of an increased risk of diabetes and ketoacidosis after using ICIs, and careful monitoring for diabetes and ketoacidosis is recommended.