Loading
Rarely, immunotherapy destroys the cells that make insulin. Blood sugar can rise within days and become dangerous (diabetic ketoacidosis). Thirst, passing a lot of urine, being sick or feeling drowsy need urgent help. It is treated with insulin, which is almost always lifelong, and not with steroids.
Rare (about 1%; 0.2 to 1.4% in the SITC 2025 definitions) but frequently serious: diabetic ketoacidosis is present at diagnosis in up to 70% (ESE 2022). Most cases follow PD-1 or PD-L1 inhibitors (76% and 8% in the series ESE cites, against 4% for CTLA-4 inhibitors); onset ranges from soon after the first dose to a year later (median 2 to 4.8 months). Autoantibodies (mostly GAD65) are found in 40 to 53%. SGLT2 inhibitors add to the risk of ketoacidosis (ESE).
Glucose is checked before every infusion and HbA1c at the start (SITC 2025 definitions). New or worsening hyperglycaemia above 11.1 mmol/L (200 mg/dL), especially without diabetes or new steroids, raises suspicion; urine ketones and blood pH screen for ketoacidosis. Ketoacidosis is treated in hospital with intravenous insulin and fluids under the usual protocols, and the checkpoint inhibitor is held until it resolves. Insulin is started urgently once the diagnosis is suspected; high-dose steroids do not help (ESE, +000). C-peptide and islet autoantibodies support the diagnosis but a normal C-peptide early on does not exclude it. Treatment is a multiple-injection insulin regimen with endocrinology referral and education; recovery is rare.
Why: This diabetes comes on quickly, so a routine glucose test is the earliest warning.
“To enable prompt identification of ir-T1DM, ICI-treated patients should undergo routine metabolic panels including glucose measurement prior to each infusion, as well as glycated hemoglobin at ICI initiation.”
Why: Steroids and type 2 diabetes are common causes of high sugar; a sudden rise without them points to the immunotherapy.
“ir-T1DM should be suspected in any patient with emergent or worsening hyperglycemia (>200 mg/dL or 11.1 mmol/L) following ICI treatment, especially in those with no history of diabetes and no new prescription of glucocorticoids, and in those with previously well-controlled T2DM.”
Why: Ketoacidosis is common at diagnosis and can be found before it becomes life-threatening.
“When hyperglycemia is present, urine ketone testing and blood pH measurement are recommended for early diagnosis of diabetic ketoacidosis (DKA).”
European Society of Endocrinology, European Journal of Endocrinology 2022
Why: Ketoacidosis needs hospital treatment, and the next dose can wait until it is under control.
“If patients experience severe hyperglycemia or DKA on ICIs, they should be hospitalized.”
Why: Immune diabetes causes a profound lack of insulin, so it is treated like any severe ketoacidosis.
“We recommend that patients presenting with DKA should be managed with i.v. insulin and fluid resuscitation according to current guidelines”
European Society of Endocrinology, European Journal of Endocrinology 2022 · good clinical practice
Why: Waiting for proof risks a hyperglycaemic crisis; the diagnosis can be revisited once the patient is stable.
“Once ir-T1DM is suspected, or if the etiology of hyperglycemia is unclear, the patient should be considered for urgent insulin initiation, to minimize the risk of hyperglycemic crisis.”
Why: Steroids do not rescue the insulin-making cells and push blood sugar higher.
“We recommend against the use of high-dose glucocorticoids for treatment of ICI-induced DM”
European Society of Endocrinology, European Journal of Endocrinology 2022 · +000
Why: These tests support the diagnosis, and the patient needs the skills to manage insulin from the start.
“Patients with new-onset diabetes (type I) should be tested for hemoglobin A1c, C-peptide, autoantibodies and counseled on diabetes management, including diet and lifestyle changes, glucose monitoring, and insulin treatment.”
Why: Insulin production can fall quickly over the first weeks.
“A detectable C-peptide should not be regarded as a reassuring result to exclude the diagnosis of ir-T1DM, as C-peptide level can decline rapidly in ir-T1DM.”
Why: The insulin-making cells rarely recover, so insulin is almost always lifelong.
“We recommend treating ICI-induced persistent DM due to islet destruction with s.c. insulin”
European Society of Endocrinology, European Journal of Endocrinology 2022 · ++00
Why: Insulin-deficient diabetes needs close glucose monitoring and dose adjustment.
“Patients with suspected or confirmed ir-T1DM should therefore be referred promptly to an endocrinologist with expertise in T1DM management.”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
SITC 2021, ESE 2022 and the SITC 2025 endocrine definitions agree: screen glucose routinely, look for ketoacidosis when glucose is high, treat ketoacidosis in hospital with intravenous insulin and fluids, start insulin early, and do not use high-dose steroids. ESE is the only one to grade its recommendations (GRADE): subcutaneous insulin for persistent diabetes ++00, no high-dose glucocorticoids +000. SITC 2021 holds the checkpoint inhibitor until ketoacidosis resolves; ESE treats a controlled endocrinopathy as no reason to stop. None of the sources read sets a glucose threshold for holding treatment other than ketoacidosis.
European Society of Endocrinology, European Journal of Endocrinology 2022 · SITC, Journal for ImmunoTherapy of Cancer 2021 · Journal for ImmunoTherapy of Cancer 2025
Where it differs: Evaluates every patient with hyperglycaemia for ketoacidosis and holds the checkpoint inhibitor until it is resolved, rather than holding for diabetes as such.
Evidence: Expert consensus; no level of evidence printed.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Intravenous insulin and fluids for ketoacidosis | good clinical practice | European Society of Endocrinology, European Journal of Endocrinology 2022 |
| No high-dose glucocorticoids for checkpoint inhibitor diabetes | +000 | European Society of Endocrinology, European Journal of Endocrinology 2022 |
| Subcutaneous insulin for persistent diabetes | ++00 | European Society of Endocrinology, European Journal of Endocrinology 2022 |
| Regular training on managing the condition, including diet and physical activity “We recommend that patients with DM are provided with appropriate and regular training on managing their condition and treatment, including diet and physical activity” | Good clinical practice | European Society of Endocrinology, European Journal of Endocrinology 2022 |
Shares Thyroid inflammation and underactive thyroid from checkpoint inhibitors, Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer and the tags protocol, irae.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, Society for Immunotherapy of Cancer, Avelumab, Tremelimumab and the tags protocol, irae.
Shares Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae, acute-oncology.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae, acute-oncology.