Expert opinion on immunotherapy induced diabetes

Area of Science:

• Oncology
• Endocrinology
• Immunology

Background:

• Immunotherapy, particularly immune checkpoint inhibitors, can cause endocrine adverse events.
• Pituitary and thyroid dysfunctions are common endocrine side effects.
• New-onset diabetes mellitus has been reported with PD-1/PD-L1 inhibitors.

Purpose of the Study:

• To investigate the occurrence and characteristics of diabetes mellitus associated with immune checkpoint inhibitors.
• To differentiate the endocrine side effect profiles of PD-1/PD-L1 inhibitors versus anti-CTLA-4 antibodies.

Main Methods:

• Review of reported cases of diabetes mellitus in patients treated with PD-1/PD-L1 inhibitors, alone or in combination with anti-CTLA-4 antibodies.
• Analysis of clinical presentation, including onset, severity, and treatment requirements.
• Comparison with the incidence of diabetes in patients receiving anti-CTLA-4 monotherapy.

Main Results:

• PD-1/PD-L1 inhibitors, alone or combined with anti-CTLA-4, are associated with sudden-onset insulinopenia.
• These cases frequently progress to ketoacidosis or fulminant diabetes, necessitating immediate insulin therapy.
• No similar adverse effect of diabetes has been reported with anti-CTLA-4 monotherapy.

Conclusions:

• Immune checkpoint inhibitors targeting PD-1/PD-L1 pathways pose a risk of severe, new-onset diabetes.
• Anti-CTLA-4 monotherapy does not appear to share this specific endocrine adverse effect.
• Close monitoring for endocrine dysfunction is crucial in patients receiving immunotherapy.