From Immunotherapy to Insulin: A Case Series of Programmed Death Ligand 1 Inhibitor-Induced Type 1 Diabetes

Document Type

Conference Proceeding

Publication Date

10-2025

Publication Title

Journal of the Endocrine Society

Abstract

Background: Type 1 diabetes (T1DM) is a rare treatment-related adverse effect of programmed-death ligand 1 (PDL-1) inhibitors, a revolutionary treatment for many types of early and advanced cancers. Patients typically present with a fulminant onset of diabetic ketoacidosis (DKA) followed by poorly controlled hyperglycemia. Case-based clinical judgment is required to balance the risks and benefits for the management of their diabetes and cancer. We present five unique cases that emphasize the importance of rapid identification and management of PDL-1-induced T1DM. Clinical Cases: We present five cases of patients with different advanced cancers who all developed T1DM after being treated with a PDL-1 inhibitor. The mean age of our patients was 80.4 years (73-88), which is much older than the median age of usual T1DM onset in their mid-20s. None had a previous history of diabetes mellitus, and only one patient had a history of autoimmune diseases (Hashimoto’s thyroiditis). The mean time of onset for developing T1DM after first exposure to their PDL-1 inhibitor was 95.2 days (56-126 days). On initial presentation, the average blood glucose was 747.6 mg/dL (452mg/ dL - 1300mg/dL) with an average HbA1c of 7.6% (5.3% - 8.4%), consistent with a rapid onset of T1DM. The most common initial complaints were fatigue, polyuria, and unintentional weight loss. Four patients had documented c-peptide levels consistent with insulinopenia, and three patients had documented positive glutamic acid decarboxylase antibodies, indicative of autoimmune diabetes. Three patients initially presented with DKA indicated by either positive urine ketones or an elevated betahydroxybutyrate, one of which was complicated by severe acute pancreatitis. All five patients required maintenance insulin therapy and continuous glucose monitoring. Three patients had difficulty maintaining glycemic control after their diagnosis, where their continuous blood glucose monitoring data showed an average time in range (TIR) of 39.6% (33.3 - 44.4%), far below the goal of >70% TIR. Two patients had at least one additional admission for DKA following their diagnosis, again suggesting poor control. The two patients who maintained reasonable glycemic control without additional DKA admissions were rechallenged with their PDL-1 inhibitor and have continued to tolerate their therapy well. Discussion: The rapid onset and management complexities of the T1DM highlighted in these patients underscore the urgent need for heightened awareness, early screening strategies, and standardized management protocols. Having appropriate glycemic control in these patients is a critical factor for determining whether they can tolerate resuming their PDL-1 inhibitor. Further research is required to elucidate the pathophysiology, identify markers, and optimize treatment approaches for this rare and serious adverse effect.

Volume

9

Issue

Suppl 1

First Page

A602

Last Page

A603

Comments

ENDO 2025 Endocrine Society Annual Meeting, July 12-15, 2025, San Francisco, CA

DOI

10.1210/jendso/bvaf149.1135

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