{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T19:07:35Z","timestamp":1768590455322,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The EmDia trial, designed to study the effects of the sodium glucose cotransporter\u20102 (SGLT2) inhibitor empagliflozin on cardiovascular comorbidities in type 2 diabetes mellitus (T2DM) patients, has been investigated for short\u2010term metabolic alterations by a limited set of clinical assays. To expand on this data, we report on the development of a liquid chromatography\u2010mass spectrometry (LC\u2010MS)\u2010based metabolomics approach employing an optimized metabolite separation by pentafluorophenyl chromatography. High\u2010confidence metabolite annotation based on reference standards allows for fast and robust metabolic characterization of large plasma cohorts due to scalability. Applied to EmDia, we show the high predictive power of our methodology for several clinical parameters, including a near\u2010perfect prediction of fasting blood glucose (\n                      <jats:italic>\n                        R\n                        <jats:sup>2<\/jats:sup>\n                      <\/jats:italic>\n                      \u00a0=\u00a00.97), and demonstrate how empagliflozin leads to reduced plasma levels of deoxyhexoses, such as 1,5\u2010anhydroglucitol, a short\u2010term biomarker for glycemic control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Clinical metabolomics studies continue to gain interest due to their comprehensive metabolite coverage, offering insights into metabolic alterations in health and disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this study, we present a robust data\u2010independent acquisition liquid chromatography\u2010mass spectrometry\u2010based metabolomics workflow employing an optimized metabolite separation by pentafluorophenyl chromatography that showcases a comprehensive coverage of plasma metabolites.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Applied to characterize plasma metabolite profiles in samples of EmDia, a placebo controlled study investigating the effect of the SGLT2 inhibitor empagliflozin, we assess the predictive power of metabolite signals for clinical parameters describing organ physiologies and pathophysiologies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Descriptive statistics are applied to the metabolite profiles to identify empagliflozin intake\u2010associated metabolite markers.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pmic.70075","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T11:49:27Z","timestamp":1764762567000},"page":"44-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Profiling of the EmDia Cohort by LC\u2010MS Reveals Empagliflozin\u2010Intake Associated Regulation of 1,5\u2010anhydroglucitol and Urate"],"prefix":"10.1002","volume":"26","author":[{"given":"Fabian","family":"Schmitt","sequence":"first","affiliation":[{"name":"Institute of Immunology University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"ten Cate","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz  Mainz Germany"},{"name":"Clinical Epidemiology and Systems Medicine Center For Thrombosis and Hemostasis (CTH)  Mainz Germany"},{"name":"German Center for Cardiovascular Research (DZHK) Partner Site Rhine\u2010Main  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zlatka","family":"Fischer","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Hagen","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara A.","family":"Steigenberger","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Core Facility Max Planck Institute of Biochemistry  Martinsried Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Tenzer","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center Johannes Gutenberg University Mainz Mainz Germany"},{"name":"Research Center for Immunotherapy (FZI) University Medical Center of the Johannes\u2010Gutenberg University  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp S.","family":"Wild","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz  Mainz Germany"},{"name":"Clinical Epidemiology 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