Development of type 1 diabetes mellitus after nivolumab dose escalation: A case report

Immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM) is a rare but serious immune-related adverse event associated with programmed cell death-1 inhibitors such as nivolumab. While previous reports have documented its occurrence, the relationship between nivolumab dosing and the onset of ICI-T1DM remains unclear. This study presents a case of ICI-T1DM following a nivolumab dose and includes a literature review.

A man in his 50s (weight: 49.4 kg, body mass index: 17.65 kg/m2) with advanced esophageal cancer had been receiving nivolumab (240 mg every 14 days) for over 2 years without adverse effects. Because of treatment adjustments, the dose was increased to 480 mg and administered every 28 days. Ninety-six days after the dose increase, he developed acute-onset fatigue, anorexia, and thirst.

Laboratory tests confirmed diabetic ketoacidosis with hyperglycemia (582 mg/dL), low C-peptide levels, and negative islet-associated antibodies, leading to the diagnosis of nivolumab-induced fulminant type 1 diabetes mellitus.

The patient was treated with insulin and discharged after stabilization.

This case suggests that higher dose nivolumab may increase the risk of ICI-T1DM, especially in low body-weight individuals.

Given that nivolumab remains effective at lower doses, dose optimization may help mitigate immune-related adverse events while maintaining therapeutic efficacy.