From the Guidelines
Immune checkpoint inhibitors can cause new-onset diabetes, and immediate insulin therapy is required to prevent life-threatening diabetic ketoacidosis (DKA) 1.
Immune Checkpoint Inhibitors and New-Onset Diabetes
Immune checkpoint inhibitors (ICIs) can cause new-onset diabetes as a rare but serious immune-related adverse event, with an incidence of less than 1% 1. This condition, known as ICI-induced diabetes, typically presents as sudden-onset type 1 diabetes with rapid beta cell destruction, often leading to diabetic ketoacidosis (DKA) 1.
Key Considerations
- The most commonly implicated ICIs include pembrolizumab, nivolumab, and ipilimumab, with anti-PD-1 and anti-PD-L1 agents carrying higher risk than CTLA-4 inhibitors 1.
- Patients on ICIs should be monitored regularly with fasting glucose or HbA1c tests before and during treatment 1.
- Early warning signs include polyuria, polydipsia, weight loss, fatigue, and nausea 1.
- If diabetes develops, immediate insulin therapy is required, typically with a basal-bolus regimen, as this condition is usually permanent and non-reversible 1.
- Unlike typical autoimmune diabetes, ICI-induced diabetes often lacks traditional autoantibodies, though glutamic acid decarboxylase (GAD) antibodies may be present in some cases 1.
Management of ICI-Induced Diabetes
- Insulin therapy should be used in any case with significant hyperglycemia pending additional diagnostic workup if the mechanism of diabetes is not known 1.
- Starting total daily requirement can be estimated at 0.3-0.4 units/kg/d, with half of daily requirements given in divided doses as prandial coverage and half administered as a once-daily long-acting insulin 1.
- Endocrinology consultation is appropriate where the diagnosis of autoimmune diabetes is suspected, even without evidence of DKA on presentation, due to the complex treatment regimen and education required for anyone with this diagnosis 1.
From the Research
Immune Checkpoint Inhibitors and New Onset Diabetes
- Immune checkpoint inhibitors (ICIs) have been associated with the development of new-onset diabetes, particularly insulin-dependent diabetes 2, 3, 4.
- The frequency of ICI-induced diabetes has been reported to be around 1.8% in patients treated with PD-1 inhibitors 2.
- Pembrolizumab, a PD-1 inhibitor, has been shown to have a higher frequency of inducing new-onset diabetes compared to nivolumab and ipilimumab 2.
- The onset of diabetes can occur rapidly, with some cases presenting with severe diabetic ketoacidosis (DKA) within a few weeks of starting ICI therapy 5.
- Autoantibodies, such as glutamic acid decarboxylase-65 (GAD65) autoantibodies, have been found to be elevated in patients with ICI-induced diabetes, suggesting an autoimmune mechanism 3, 5.
- The management of ICI-induced diabetes typically involves insulin therapy, and in some cases, the addition of metformin may be necessary to achieve adequate glucose control 6.
- It is essential to monitor patients treated with ICIs for the development of new-onset diabetes and to collaborate with specialists and primary care physicians for early diagnosis and supportive care 5.