Immune Checkpoint Inhibitors and Risk of Type 1 Diabetes

Background: Type 1 diabetes mellitus (T1DM) is a rare, irreversible immune-related adverse event reported in patients receiving treatment with immune-checkpoint inhibitors (ICI). However, clinical risk factors for ICI-induced T1DM (ICI-T1DM) and its impact on survival in patients remain unknown.

Methods: We used de-identified Optum’s Clinformatics® Datamart Database to assess the incidence and characteristics of T1DM in a large cohort of patients treated with ICI between 2017-2020. We applied Fine-Gray and cause-specific hazard models to study associations between patient/treatment characteristics and ICI-T1DM and applied the Cox model with ICI-T1DM as a time-varying covariate to assess the impact of ICI-T1DM on survival.

Results: ICI-T1DM was observed in 261/30,337 (0.86%) patients. Dual use of anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) was associated with increasing risk of ICI-T1DM (HR=1.62; 95% CI, 1.15-2.26) vs. anti-PD-L1 or anti-PD1 alone. Younger age (HR=1.19 for every 5-year decrease; 95% CI, 1.13-1.25) and pre-existing non-T1DM diabetes (HR=4.48; 95% CI, 3.45-5.83) were also associated with higher risk of ICI-T1DM. Conversely, prior use of immunosuppressive medications (HR=0.57; 95% CI, 0.34-0.95) was associated with lower incidence of ICI-T1DM, but part of its protective effect may be due to the increased mortality rate. Development of ICI-T1DM doesn’t seem to significantly impact patient survival.

Conclusions: The risk of ICI-T1DM is associated with the type of ICI therapy, patient age, and pre-existing non-T1DM diabetes. These data may help guide risk assessment and screening practices of patients during ICI therapy.