Pembrolizumab-induced fulminant type 1 diabetes mellitus: a case report and literature review

A new *Frontiers in Endocrinology* paper reports a rare case of fulminant type 1 diabetes mellitus linked to pembrolizumab, an immune checkpoint inhibitor widely used in cancer treatment. The case involved a young man with clear cell renal cell carcinoma and suspected lung metastases, with a prior history of hypothyroidism but no family history of diabetes. After 22 cycles of pembrolizumab, he developed lethargy and severe metabolic acidosis, with markedly elevated blood glucose, HbA1c of 6.7%, and extremely low C-peptide levels.

The authors diagnosed immune checkpoint inhibitor-associated fulminant type 1 diabetes. The patient improved after fluid resuscitation and insulin therapy, then continued pembrolizumab for three more cycles before the drug was permanently stopped. The report also reviewed 32 confirmed cases of pembrolizumab-associated fulminant type 1 diabetes. Most cases involved patients treated for lung cancer or melanoma, and onset ranged widely from 1 to 24 treatment cycles.

The key takeaway is that this adverse event is rare but potentially severe, often presenting abruptly with insulin deficiency and diabetic ketoacidosis. The review found that GADA-positive patients tended to develop fulminant type 1 diabetes earlier, and thyroid dysfunction occurred before or at the same time as fulminant diabetes in 90% of reported cases. The authors argue for continued metabolic monitoring throughout pembrolizumab therapy and follow-up for additional endocrine dysfunction after diagnosis. For clinicians, the paper is a reminder that cancer immunotherapy can trigger sudden autoimmune diabetes requiring long-term insulin treatment.