Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: a case report and systematic review

Front Public Health. 2023 Dec 1:11:1264056. doi: 10.3389/fpubh.2023.1264056. eCollection 2023.

Abstract

Objective: Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered diabetes is insulin, but a detailed therapeutic method has not yet been established. To prevent severe symptoms and mortality of diabetic ketoacidosis in advanced-stage cancer patients, the establishment of effective treatment of CPI-triggered diabetes, other than insulin therapy, is required.

Methods: We present a case of a 76-year-old man with CPI-triggered diabetes who was treated with nivolumab and ipilimumab for lung cancer. We also conducted a systematic review of 48 case reports of type 1 diabetes associated with nivolumab and ipilimumab therapy before June 2023.

Results: The patient's hyperglycemia was not sufficiently controlled by insulin therapy, and after the remission of ketoacidosis, the addition of a sodium-glucose transporter (SGLT) 2 inhibitor, dapagliflozin, improved glycemic control. Most of the reported nivolumab/ipilimumab-induced type 1 diabetes was treatable with insulin, but very few cases required additional oral anti-diabetic agents to obtain good glucose control.

Conclusion: Although SGLT2 inhibitors have been reported to have adverse effects on ketoacidosis, recent studies indicate that the occurrence of ketoacidosis is relatively rare. Considering the pathological mechanism of CPI-triggered diabetes, SGLT2 inhibitors could be an effective choice if they are administered while carefully monitoring the patient's ketoacidosis.

Keywords: SGLT2 inhibitor; diabetes; insulin; ipilimumab; nivolumab.

Publication types

  • Systematic Review
  • Case Reports

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 1* / chemically induced
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetic Ketoacidosis* / chemically induced
  • Diabetic Ketoacidosis* / drug therapy
  • Humans
  • Insulin / adverse effects
  • Ipilimumab / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Male
  • Nivolumab / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects

Substances

  • Nivolumab
  • Sodium-Glucose Transporter 2 Inhibitors
  • Ipilimumab
  • Insulin

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.