Immune checkpoint inhibitor-associated diabetes mellitus: an overlooked immune-related adverse event—two case reports and a literature review

Abstract

Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a relatively uncommon manifestation of immune-related adverse events. However, it often presents with diabetic ketoacidosis (DKA) at onset, which may lead to severe and potentially life-threatening complications. Therefore, early recognition and treatment are essential. This condition typically occurs within the first three months after initiation of immunotherapy, whereas delayed onset after treatment discontinuation has been infrequently reported. In this study, Case 1 developed diabetic ketoacidosis 9 weeks after discontinuation of serplulimab (approximately 19 months after treatment initiation), representing a rare delayed-onset presentation. Case 2 developed hyperglycemia after 23 weeks of envafolimab therapy and exhibited preserved islet function without DKA, suggesting a possible early-stage or type 2 diabetes-like phenotype of ICI-related dysglycemia. Both patients achieved glycemic control with exogenous insulin therapy. Immunotherapy was discontinued in Case 1, whereas Case 2 continued treatment with satisfactory glycemic control. This study summarizes the pathogenesis, clinical characteristics, management, and prognosis of ICI-DM, highlighting its heterogeneity and the importance of early detection of ICI-related dysglycemia. Early and continuous glucose monitoring during and after immunotherapy is essential, and ongoing follow-up after treatment discontinuation remains warranted.