{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:00Z","timestamp":1787027280157,"version":"build-2736575974"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The patient\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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\u2019s ketoacidosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2023.1264056","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T13:00:53Z","timestamp":1701435653000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: a case report and systematic review"],"prefix":"10.3389","volume":"11","author":[{"given":"Makoto","family":"Fujiwara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Okano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Maejima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenju","family":"Shimomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"452","DOI":"10.2174\/156800961506150805145120","article-title":"Immune checkpoint inhibitors for Cancer therapy: clinical efficacy and safety","volume":"15","author":"Azoury","year":"2015","journal-title":"Curr Cancer Drug Targets"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1056\/NEJMp1510079","article-title":"Releasing the brakes on Cancer immunotherapy","volume":"373","author":"Ribas","year":"2015","journal-title":"N Engl J Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1056\/NEJMe1205943","article-title":"Tumor immunotherapy directed at PD-1","volume":"366","author":"Ribas","year":"2012","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1093\/intimm\/dxm057","article-title":"PD-1 and PD-1 ligands: from discovery to clinical application","volume":"19","author":"Okazaki","year":"2007","journal-title":"Int Immunol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nrendo.2016.205","article-title":"Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies","volume":"13","author":"Byun","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3144","DOI":"10.1210\/jc.2018-00728","article-title":"Programmed cell Death-1 inhibitor-induced type 1 diabetes mellitus","volume":"103","author":"Clotman","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.2337\/dbi18-0002","article-title":"Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors","volume":"67","author":"Stamatouli","year":"2018","journal-title":"Diabetes"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1111\/dme.14050","article-title":"Immune checkpoint inhibitor-induced type 1 diabetes: a systematic review and meta-analysis","volume":"36","author":"Akturk","year":"2019","journal-title":"Diabet Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"5499","DOI":"10.1210\/jc.2019-00423","article-title":"Checkpoint inhibitor-associated autoimmune diabetes is distinct from type 1 diabetes","volume":"104","author":"Tsang","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e000591","DOI":"10.1136\/bmjdrc-2018-000591","article-title":"Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes","volume":"7","author":"Kotwal","year":"2019","journal-title":"BMJ Open Diabetes Res Care"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"iv119","DOI":"10.1093\/annonc\/mdx225","article-title":"ESMO guidelines committee. 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