Review of immune checkpoint inhibitor-associated diabetes mellitus in two patients

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Frontiers in Medicine Published May 9, 2026 Medically reviewed May 9, 2026 Study authors: Mengjia He, Zhenru Zheng, Xiaofan Guo, Gang Cheng, Shuang Zhang, Jinlong Liu, Jing Zhao DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider early and continuous glucose monitoring for patients on immune checkpoint inhibitors due to risk of diabetes.

This is a narrative review and case report describing two patients with immune checkpoint inhibitor-associated diabetes mellitus. The scope covers the clinical presentation and management of diabetes related to serplulimab and envafolimab therapy. The authors report that immune checkpoint inhibitor-associated diabetes mellitus typically occurs within the first three months after initiation, but delayed onset after treatment discontinuation has been infrequently reported. In Case 1, diabetic ketoacidosis developed 9 weeks after discontinuation of serplulimab, approximately 19 months after treatment initiation. In Case 2, hyperglycemia developed after 23 weeks of envafolimab therapy, with preserved islet function without diabetic ketoacidosis, suggesting a possible early-stage or type 2 diabetes-like phenotype. Both patients achieved glycemic control with exogenous insulin therapy. Immunotherapy was discontinued in Case 1, whereas Case 2 continued treatment with satisfactory glycemic control. The authors note that ongoing follow-up after treatment discontinuation remains warranted. Limitations include the small sample size of two patients and the lack of a comparator group. Practice relevance emphasizes early and continuous glucose monitoring during and after immunotherapy.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original 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.