Dual immune checkpoint inhibitor therapy significantly increases risk of developing Type 1 Diabetes MellitusDual immune checkpoint inhibitor therapy increases risk of type 1 diabetes

Immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM) is a rare but potentially life-threatening endocrine immune-related adverse event. However, data on its incidence, risk factors, and prognostic implications remain limited. We conducted a systematic review and meta-analysis of studies published since January 2020 that reported ICI-T1DM in adult cancer patients treated with immune checkpoint inhibitors (ICIs). Pooled proportions were estimated for ICI-T1DM incidence and diabetic ketoacidosis (DKA) occurrence. Odds ratios (ORs) and hazard ratios (HRs) were pooled to evaluate the association of dual versus monotherapy ICI exposure and pre-existing diabetes mellitus with the risk of developing ICI-T1DM and prognostic outcomes. Risk of bias was assessed using validated design-specific tools. Ten studies involving 65,925 ICI-treated patients were included. The pooled incidence of ICI-T1DM was 0.58% (95% CI 0.35-0.92%), while approximately 37% of patients presented with DKA. Dual ICI therapy significantly increased the risk of ICI-T1DM compared with monotherapy. Pre-existing diabetes mellitus was not significantly associated with the risk of developing ICI-T1DM. Available prognostic data for mortality and overall survival in patients who developed ICI-T1DM were limited to two studies with discordant findings and a substantial risk of immortal time bias, precluding meaningful quantitative synthesis. These findings support routine glucose monitoring during ICI therapy, particularly for patients receiving combination regimens. The potential role of pre-treatment islet autoantibody testing in selected high-risk patients warrants prospective evaluation.