AUTHOR=Fujiwara Makoto , Shimizu Masaru , Okano Tatsuya , Maejima Yuko , Shimomura Kenju 

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

JOURNAL=Frontiers in Public Health

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1264056

DOI=10.3389/fpubh.2023.1264056

ISSN=2296-2565

ABSTRACT=Objective: Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPIs-triggered diabetes mellitus.  The typical treatment for CPIs-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 CPIs-triggered diabetes, other than insulin therapy is required.  
Methods: We present a case of a 76 year-old-male with CPIs-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.
Conclusions: Although SGLT-2 inhibitors have been reported to have adverse effects of ketoacidosis, recent studies indicate that the occurrence of ketoacidosis is relatively rare. Considering the pathological mechanism of CPIs-triggered diabetes, SGLT-2 inhibitors could be an effective choice if they are administered while carefully monitoring the patient’s ketoacidosis.