{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:55:21Z","timestamp":1790654121470,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08DK142012"],"award-info":[{"award-number":["K08DK142012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K12DK133995"],"award-info":[{"award-number":["K12DK133995"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32DK007120"],"award-info":[{"award-number":["T32DK007120"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23 HL179482"],"award-info":[{"award-number":["K23 HL179482"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002345"],"award-info":[{"award-number":["UL1TR002345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["KL2TR002346"],"award-info":[{"award-number":["KL2TR002346"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Use of sodium\u2010glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 1 diabetes (T1D) is limited by increased risk of ketoacidosis. We aimed to determine metabolic pathways affected by SGLT2i treatment in adults with T1D during ketosis induced by insulin withdrawal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Plasma metabolomic and lipidomic analysis by ultra\u2010high\u2010performance liquid chromatography\/mass spectrometry was performed at baseline and after supervised insulin withdrawal in 17 adults with T1D treated with usual care (UC) and (DP) dapagliflozin (10\u2009mg daily for 14\u2009days).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma glucose levels were lower, and ketone levels were higher after insulin withdrawal in DP compared to UC. Pathway analysis of differentially altered metabolites revealed that DP altered amino acids and TCA cycle metabolites during ketosis. DP treatment increased citrate and aconitate at baseline, with a trend towards increased branched chain ketoacids and acylcarnitines. Citrate, aconitate, \u03b1\u2010ketoglutarate and malate were increased during insulin withdrawal after UC whereas insulin withdrawal after DP resulted in unchanged \u03b1\u2010ketoglutarate and malate and significantly decreased fumarate and succinate. Acetylcarnitine was significantly higher during insulin withdrawal after DP compared to UC. DP effected subtle changes in amino acids and amino acid derivatives. Symmetric dimethylarginine and pseudouridine were significantly elevated at baseline and after insulin withdrawal after DP. Lipidomics revealed increased very long TG species in DP and differences in phospholipids, particularly phosphatidylcholine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In adults with T1D, dapagliflozin alters TCA cycle metabolites, amino acid metabolites and certain lipids during insulin withdrawal. Future work will validate findings and further investigate the metabolic basis of SGLT2i\u2010mediated ketoacidosis risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71390","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:07:30Z","timestamp":1790651250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dapagliflozin Alters Plasma Metabolome in Patients With Type 1 Diabetes During Ketosis"],"prefix":"10.1111","author":[{"given":"Rosa","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism, &amp; Lipid Research Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Cho","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Medicine, and the Center for Mass Spectrometry &amp; Metabolic Tracing Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8646-2377","authenticated-orcid":false,"given":"Max C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, &amp; Lipid Research Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai E.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, &amp; Lipid Research Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Patti","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Medicine, and the Center for Mass Spectrometry &amp; Metabolic Tracing Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet B.","family":"McGill","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, &amp; Lipid Research Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9984-7046","authenticated-orcid":false,"given":"Samantha A.","family":"DiGruccio","sequence":"additional","affiliation":[{"name":"Division of Endocrinology &amp; Metabolism University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes","volume":"373","author":"Zinman B.","year":"2015","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1161\/CIRCULATIONAHA.118.034222","article-title":"Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program","volume":"138","author":"R\u00e5dholm K.","year":"2018","journal-title":"Circulation"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/dom.12829","article-title":"Rationale, Design and Baseline Characteristics of the CANagliflozin cardioVascular Assessment Study\u2010Renal (CANVAS\u2010R): A Randomized, Placebo\u2010Controlled Trial","volume":"19","author":"Neal B.","year":"2017","journal-title":"Diabetes, Obesity & Metabolism"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(18)32590-X","article-title":"SGLT2 Inhibitors for Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Systematic Review and Meta\u2010Analysis of Cardiovascular Outcome Trials","volume":"393","author":"Zelniker T. 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