Minyoung Lee^a,b,1, Kyeongseob Jeong^c,1, Yu Rang Park^c, Yumie Rhee^a,b

^aDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
^bInstitute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea
^cDepartment of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea

¹These authors are co-first authors.
Corresponding authors: Yu Rang Park, Yumie Rhee

Aims/hypothesis
Immune checkpoint inhibitor (ICI) has been emerged as a promising cancer treatment. However, ICI use induces immune-related adverse events, including diabetes mellitus. We compared the risk of new-onset diabetes between patients receiving an ICI and those receiving conventional chemotherapy (CC).

Methods
Using a tertiary care hospital database, we included cancer patients without a previous history of diabetes who were treated with either CC or an ICI. One-to-five nearest neighbor propensity matching was applied, and the risk of diabetes was estimated using a Cox proportional hazards model. Latent class growth modeling was performed with a trajectory approach to determine distinct clusters that followed similar glucose trajectory patterns over time.

Results
Among 1326 subjects, 1105 received CC, and 221 received an ICI. The risk of new-onset diabetes was significantly higher in the ICI group than the CC group (adjusted hazard ratio 2.454, 95 % confidence interval 1.528–3.940; p < 0.001). The ICI group had a higher proportion of subjects in the trajectory cluster with an increasing glucose pattern than the CC group (10.4 % and 7.4 %, respectively). Within the ICI group, the subjects with an increasing glucose pattern were predominantly male and associated with enhanced lymphocytosis after ICI administration.

Conclusions
ICI therapy is associated with an increased risk of incident diabetes compared with CC. The glucose levels of patients treated with an ICI, especially males and those with prominent lymphocytosis after ICI treatment, need to be monitored regularly to detect ICI-associated diabetes as early as possible.