Pembrolizumab-Associated Insulinopenic Diabetes Mellitus Presenting without Ketoacidosis and Mimicking Type 2 Diabetes Mellitus

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for several solid organ malignancies, but immune activation may also lead to immune-related adverse events involving endocrine organs. Pembrolizumab is an IgG4 monoclonal antibody targeting programmed cell death protein-1. Although checkpoint inhibitor-associated diabetes mellitus (CIADM) is uncommon, it is clinically important because many reported cases present abruptly with severe insulin deficiency and diabetic ketoacidosis (DKA). We report a 52-year-old woman with metastatic cervical cancer in remission who developed severe hyperglycemia without biochemical evidence of DKA or hyperosmolar hyperglycemic state. Because of her obese phenotype and non-ketotic presentation, she was initially managed as having type 2 diabetes mellitus with metformin, dapagliflozin, semaglutide, and basal insulin. Persistent marked hyperglycemia despite treatment led to reconsideration of the diagnosis. Further review confirmed prior pembrolizumab exposure, and testing showed persistently low fasting C-peptide levels with negative glutamic acid decarboxylase, islet cell, and insulin autoantibodies. Her glycemic control improved after transition to a basal-bolus insulin regimen. This case highlights that probable pembrolizumab-associated insulinopenic diabetes can mimic type 2 diabetes, may occur without DKA, and should be considered in patients with prior ICI exposure who have severe or treatment-resistant hyperglycemia.