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Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Euglycemic diabetic ketoacidosis (euDKA) is a rare but potentially life-threatening complication of diabetes, increasingly linked to SGLT-2 inhibitors (SGLT-2i) and, less frequently, GLP-1 receptor agonists (GLP-1 RA), especially in combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>We present the case of a 36-year-old man with newly diagnosed type 2 diabetes who developed severe euDKA within days of starting combined therapy with semaglutide and dapagliflozin. Despite prior patient education and adherence to antidiabetic therapy, persistent vomiting and carbohydrate deficiency\u2014likely related to GLP-1 RA side effects\u2014led to decreased insulin administration and metabolic decompensation. This case was characterized by very early onset after initiation of therapy, absence of infection or other common triggers, and resistance to standard treatment with insulin, glucose, and fluid resuscitation. Intensive care with continuous veno-venous hemodiafiltration was required, resulting in full recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case emphasizes the potential severity of euDKA induced by GLP-1 RA and SGLT-2i combination therapy and highlights the risk of treatment resistance. The decision to initiate SGLT2i and GLP-1RA concurrently should be individualized or possibly spread apart in time, weighing the potential therapeutic benefits against the risk of rare but severe complication such as euDKA. Comprehensive education on ketone monitoring and insulin administration during intercurrent illness are essential to prevent this rare but serious complication.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1649270","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:36:20Z","timestamp":1759815380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Severe euglycemic ketoacidosis following combined therapy with GLP-1 receptor agonist and SGLT-2 inhibitor, refractory to standard treatment: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Agnieszka","family":"Gandecka-Pempera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Naskr\u0119t","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Adamska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Zozuli\u0144ska-Zi\u00f3\u0142kiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2020.06.059","article-title":"Evaluation and management of the critically ill adult with diabetic ketoacidosis","volume":"59","author":"Long","year":"2020","journal-title":"J Emerg Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"7074868","DOI":"10.1155\/2018\/7074868","article-title":"Newer perspectives of mechanisms for euglycemic diabetic ketoacidosis","volume":"2018","author":"Yu","year":"2018","journal-title":"Int J Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2174\/1573399812666160421121307","article-title":"Euglycemic diabetic ketoacidosis: A review","volume":"13","author":"Modi","year":"2017","journal-title":"Curr Diabetes Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1530\/EDM-17-0081","article-title":"Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma","volume":"2017","author":"Rawla","year":"2017","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11892-020-01307-x","article-title":"Euglycemic ketoacidosis","volume":"20","author":"Bonora","year":"2020","journal-title":"Curr Diabetes Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5866.578","article-title":"Euglycemic diabetic ketoacidosis","volume":"2","author":"Munro","year":"1973","journal-title":"Br Med J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/BF00569937","article-title":"Euglycemic diabetic ketoacidosis: does it exist","volume":"30","author":"Jenkins","year":"1993","journal-title":"Acta Diabetol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ejim.2019.03.014","article-title":"Euglycemic diabetic ketoacidosis","volume":"63","author":"Barski","year":"2019","journal-title":"Eur J Intern Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2023-003666","article-title":"Euglycemic diabetic ketoacidosis in the era of SGLT-2 inhibitors","volume":"11","author":"Chow","year":"2023","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B11","doi-asserted-by":"publisher","first-page":"A1750","DOI":"10.1016\/j.chest.2023.07.1206","article-title":"Clinical impact of sglt2 inhibitors and euglycemic diabetic ketoacidosis: insights from the faers database","volume":"164","author":"Vallabhajosyula","year":"2023","journal-title":"Chest."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2024.0036","article-title":"Diabetic ketoacidosis as an effect of sodium-glucose cotransporter 2 inhibitor: real world insights","volume":"48","author":"Baek","year":"2024","journal-title":"Diabetes Metab J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"100139","DOI":"10.1016\/j.jemrpt.2025.100139","article-title":"Acute pancreatitis and euglycemic non-diabetic ketoacidosis caused by an intentional semaglutide overdose","volume":"4","author":"Acosta","year":"2025","journal-title":"JEM Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"luae156","DOI":"10.1210\/jcemcr\/luae156","article-title":"Euglycemic ketoacidosis from semaglutide in a patient without diabetes","volume":"2","author":"Sood","year":"2024","journal-title":"JCEM Case Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5114\/ctd\/203685","article-title":"Standards of care in diabetes. 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