{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:08:27Z","timestamp":1793254107020,"version":"4.5.0"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:sec id=\"ab-cbr250009-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Immune-related adverse events (IRAEs) limit the use of cancer immunotherapy. Understanding the risk of severe IRAEs may help improve the use of cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr250009-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To review and assess hyperglycemic events across thousands of patients to characterize immune checkpoint inhibitor (ICI)\u2013induced diabetes (ICI-D) using a large-scale trial conglomerate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr250009-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>Adverse event (AE) reports related to diabetes, hyperglycemia, and acidosis were retrieved from the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) database. Trial data from June 2015 to December 2022 were analyzed. Clinical information was manually retrieved. Overall counts of patients on each trial were retrieved from central NCI data. NCI CTEP trials are hosted in both academic and community medical centers. This analysis includes patients across 158 trials who were treated with varying regimens that included programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 (PD-L1) inhibitors through an NCI CTEP trial for their cancer from June 2015 to December 2022. Data clarifications were requested and then data were analyzed from January 2023 to June 1, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr250009-7\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Clinical characteristics differentiating ICI-D from other causes of hyperglycemia were enumerated. Cumulative incidence rates of ICI-D were calculated using trial-level data. Logistic regression was used to calculate the odds of developing ICI-D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr250009-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 13\u202f966 patients across 158 trials, the overall cumulative incidence of ICI-D was low (0.52 per 100 treated patients), but incidence varied by treatment type and was lower if patients were exposed to concurrent chemotherapy (0.65% without chemotherapy vs 0.26% with chemotherapy; odds ratio [OR], 0.38; 95% CI, 0.21-0.71;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.002) and higher if patients were exposed to combined immunotherapy (0.94% with combination immunotherapy vs 0.37% with PD-1\/PD-L1 inhibitor monotherapy; OR, 2.68; 95% CI, 1.69-4.24). Despite these low rates, the health care burden of ICI-D was high, with 90% requiring hospitalization at diagnosis and 43% requiring intensive care. The degree of hyperglycemia can be used to differentiate different etiologies of hyperglycemia, with higher glucose levels being more likely to be due to ICI-D.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr250009-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results of this study suggest that ICI-D is a rare but morbid condition that varies based on the combination of ICIs with other agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2025.5594","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T16:30:48Z","timestamp":1766766648000},"page":"194","source":"Crossref","is-referenced-by-count":7,"title":["Immune Checkpoint Inhibitor\u2013Induced Diabetes Across National Cancer Institute Trials That Included PD-1 or PD-L1 Agents"],"prefix":"10.1001","volume":"12","author":[{"given":"Zoe E.","family":"Quandt","sequence":"first","affiliation":[{"name":"Diabetes Center, University of California, San Francisco"},{"name":"Department of Medicine, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanda","family":"Finnigan","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Hill","sequence":"additional","affiliation":[{"name":"University of California, Santa Barbara"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe E.","family":"Dib","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Burian","sequence":"additional","affiliation":[{"name":"University of Maryland, College Park"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sapir","family":"Tessler","sequence":"additional","affiliation":[{"name":"University of Maryland, College Park"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darah","family":"Davidson","sequence":"additional","affiliation":[{"name":"University of Maryland, College Park"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Rafeh","family":"Naqash","sequence":"additional","affiliation":[{"name":"Medical Oncology\/TSET Phase 1 program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California, San Francisco"},{"name":"Department of Medicine, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Othus","sequence":"additional","affiliation":[{"name":"SWOG Statistical Center, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elad","family":"Sharon","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana Farber Cancer Institute\/Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"6","key":"cbr250009r1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/S2213-8587(19)30072-5","article-title":"Checkpoint inhibitor-induced insulin-dependent diabetes: an emerging syndrome.","volume":"7","author":"Perdigoto","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"8","key":"cbr250009r2","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"},{"issue":"11","key":"cbr250009r3","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"},{"issue":"1","key":"cbr250009r4","doi-asserted-by":"publisher","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"},{"issue":"2","key":"cbr250009r5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s11154-020-09618-w","article-title":"Diabetes mellitus induced by immune checkpoint inhibitors: type 1 diabetes variant or new clinical entity? Review of the literature.","volume":"22","author":"Lo Preiato","year":"2021","journal-title":"Rev Endocr Metab Disord"},{"key":"cbr250009r6","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev-med-050219-034237","article-title":"Autoimmune endocrinopathies: an emerging complication of immune checkpoint inhibitors.","volume":"72","author":"Quandt","year":"2021","journal-title":"Annu Rev Med"},{"issue":"12","key":"cbr250009r7","doi-asserted-by":"publisher","first-page":"e150","DOI":"10.2337\/dc18-1465","article-title":"Increased reporting of immune checkpoint inhibitor-associated diabetes.","volume":"41","author":"Wright","year":"2018","journal-title":"Diabetes Care"},{"issue":"1","key":"cbr250009r8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma.","volume":"373","author":"Larkin","year":"2015","journal-title":"N Engl J Med"},{"issue":"12","key":"cbr250009r9","doi-asserted-by":"publisher","first-page":"3106","DOI":"10.2337\/dc20-0609","article-title":"Immune checkpoint inhibitor\u2013associated diabetes: a single-institution experience.","volume":"43","author":"Byun","year":"2020","journal-title":"Diabetes Care"},{"issue":"9","key":"cbr250009r10","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"},{"issue":"10","key":"cbr250009r11","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1001\/jamaoncol.2024.3104","article-title":"Identification of immune checkpoint inhibitor-induced diabetes.","volume":"10","author":"Ruiz-Esteves","year":"2024","journal-title":"JAMA Oncol"},{"issue":"5","key":"cbr250009r12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1136\/jitc-2025-011545","article-title":"Associations between immune checkpoint inhibitor response, immune-related adverse events, and steroid use in RADIOHEAD: a prospective pan-tumor cohort study.","volume":"13","author":"Quandt","year":"2025","journal-title":"J Immunother Cancer"},{"issue":"8","key":"cbr250009r13","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.2337\/dci24-0032","article-title":"Hyperglycemic crises in adults with diabetes: a consensus report.","volume":"47","author":"Umpierrez","year":"2024","journal-title":"Diabetes Care"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2843281\/jamaoncology_quandt_2025_br_250009_1771446085.61041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:01:10Z","timestamp":1771516870000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2843281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":13,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2025.5594","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2,1]]}}}