{ "abstract": "Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2is) exert metabolic and renal effects extending beyond glycemic control, yet their relationship with circulating trace-element profiles remains poorly characterized. We investigated whether prevalent SGLT2i use was associated with differences in serum trace elements and targeted metabolites, with particular attention to renal function and the possibility of a shared multielement phenotype. Methods: In this exploratory cross-sectional study, serum trace elements and targeted amino acid metabolites were evaluated according to prevalent SGLT2i exposure. The principal clinical comparison comprised participants with diabetes mellitus (DM) receiving SGLT2i (n = 6) versus those not receiving SGLT2i (n = 10). Secondary analyses incorporated the broader three-group cohort. Because of the small exposed group and nonrandom treatment allocation, analyses were considered hypothesis-generating. Group comparisons were complemented by permutation testing, regression adjusted for recalculated uncapped 2021 CKD-EPI estimated glomerular filtration rate (eGFR), false-discovery-rate correction, inter-element correlation analysis, principal-component analysis, and influence diagnostics. Results: Among participants with DM, circulating Cu, Mg, Se, and Zn concentrations were lower in SGLT2i users, with concordant directions across complementary analyses. In the secondary analysis incorporating multiplicity correction across eight molecular outcomes, Cu (q = 0.015) and Se (q = 0.047) met the prespecified FDR threshold, whereas Mg and Zn did not (both q = 0.051). Exploratory principal-component analysis identified a first component explaining 70.8% of the variance across the four measured elements. PC1 was lower among SGLT2i-treated participants and remained associated with exposure after eGFR adjustment (β = −2.43, 95% CI −4.22 to −0.65; p = 0.008); however, this component represents statistical covariance only and should not be interpreted as evidence of a common biological mechanism or shared trace-element depletion. Conclusions: Prevalent SGLT2i use among participants with DM was associated with directionally lower circulating concentrations across several measured trace elements; however, after multiplicity correction, only Cu and Se met the prespecified FDR threshold, whereas Mg and Zn did not. The cross-sectional design, small exposed subgroup, clinical imbalance, and absence of pretreatment, dietary, urinary trace element, inflammatory, treatment duration, and adherence data preclude attribution of this pattern to SGLT2 inhibition. These findings should therefore be considered hypothesis-generating and warrant prospective validation with serial pre- and post-treatment measurements to determine whether the observed phenotype reflects pharmacological effects, treatment selection, the underlying clinical phenotype, or a combination of these factors.", "abstract_shown": true, "affiliations": [ "Department of Hypertensiology, Angiology, and Internal Medicine, Poznan University of Medical Sciences, ½ Dluga Street, 61-848 Poznan, Poland", "College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea", "Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy", "Department of Research, IRCCS ISMETT, 90127 Palermo, Italy", "Thoracic Research Center, Collegium Medicum, Nicolaus Copernicus University, 85-067 Bydgoszcz, Poland", "Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland", "College of Medicine, Inje University, 75 Bokji-ro, Busanjin-gu, Busan 47392, Republic of Korea", "Centre for Innovative Pharmaceutical Technology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland", "Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, 61-614 Poznan, Poland", "Department of Vascular, Endovascular Surgery, Angiology and Phlebology, Poznan University of Medical Sciences, ½ Dluga Street, 61-848 Poznan, Poland", "Department of Trace Analysis, Faculty of Chemistry, Adam Mickiewicz University, 61-614 Poznan, Poland", "Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, ½ Długa, 61-848 Poznan, Poland" ], "article_type": null, "arxiv": null, "author_total": 14, "authors": [ { "affs": [ 0 ], "name": "Beata Krasińska", "orcid": "0000-0002-3464-1645" }, { "affs": [ 1 ], "name": "Minseung Kang", "orcid": "0009-0001-6144-5543" }, { "affs": [ 2, 3 ], "name": "Giuseppe Maria Raffa", "orcid": "0000-0001-7141-2561" }, { "affs": [ 2, 3 ], "name": "Calogera Pisano", "orcid": "0000-0002-6488-1965" }, { "affs": [ 2, 4, 5 ], "name": "Mariusz Kowalewski", "orcid": "0000-0002-5478-3245" }, { "affs": [ 6 ], "name": "Siwon Baek" }, { "affs": [ 5 ], "name": "Piotr Suwalski" }, { "affs": [ 7 ], "name": "Dagmara Pietkiewicz" }, { "affs": [ 8 ], "name": "Szymon Plewa", "orcid": "0000-0002-9600-3980" }, { "affs": [ 8 ], "name": "Jan Matysiak", "orcid": "0000-0002-9993-1504" }, { "affs": [ 9 ], "name": "Zbigniew Krasiński", "orcid": "0000-0002-2798-1959" }, { "affs": [ 10 ], "name": "Julia Frąckowiak", "orcid": "0009-0001-8858-3188" }, { "affs": [ 10 ], "name": "Anetta Hanć" }, { "affs": [ 2, 3, 11 ], "name": "Tomasz Urbanowicz", "orcid": "0000-0001-8080-2764" } ], "bibtex": "https://research.draconitic.com/paper/5ab28r2sny9km.bib", "cited_by": 0, "doi": "10.3390/nu18213510", "fulltext_url": null, "id": "5ab28r2sny9km", "issns": [ "2072-6643" ], "landing_url": "https://www.mdpi.com/2072-6643/18/21/3510", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2916|Trace Elements in Health" ] ], "openalex": "W7223662990", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-25", "publisher": "MDPI AG", "ris": "https://research.draconitic.com/paper/5ab28r2sny9km.ris", "sources": [ { "first_seen": "2026-10-30T12:19:56Z", "native_id": "10.3390/nu18213510", "source": "crossref", "url": "https://www.mdpi.com/2072-6643/18/21/3510" } ], "subjects": [ { "field": "medicine", "origin": "issn:2072-6643", "subfield": "nutrition" } ], "title": "Lower Circulating Trace-Element Concentrations Among SGLT2 Inhibitor Users with Diabetes: An Exploratory Cross-Sectional Study", "title_text": "Lower Circulating Trace-Element Concentrations Among SGLT2 Inhibitor Users with Diabetes: An Exploratory Cross-Sectional Study", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:56Z", "url": "https://research.draconitic.com/paper/5ab28r2sny9km", "venue": "Nutrients", "versions": [] }