Lower Circulating Trace-Element Concentrations Among SGLT2 Inhibitor Users with Diabetes: An Exploratory Cross-Sectional Study

@article{krasinska2026lower,
  title = {{Lower Circulating Trace-Element Concentrations Among SGLT2 Inhibitor Users with Diabetes: An Exploratory Cross-Sectional Study}},
  author = {Beata Krasińska and Minseung Kang and Giuseppe Maria Raffa and Calogera Pisano and Mariusz Kowalewski and Siwon Baek and Piotr Suwalski and Dagmara Pietkiewicz and Szymon Plewa and Jan Matysiak and Zbigniew Krasiński and Julia Frąckowiak and Anetta Hanć and Tomasz Urbanowicz},
  journal = {Nutrients},
  year = {2026},
  month = oct,
  doi = {10.3390/nu18213510},
  url = {https://www.mdpi.com/2072-6643/18/21/3510},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Lower Circulating Trace-Element Concentrations Among SGLT2 Inhibitor Users with Diabetes: An Exploratory Cross-Sectional Study
AU  - Beata Krasińska
AU  - Minseung Kang
AU  - Giuseppe Maria Raffa
AU  - Calogera Pisano
AU  - Mariusz Kowalewski
AU  - Siwon Baek
AU  - Piotr Suwalski
AU  - Dagmara Pietkiewicz
AU  - Szymon Plewa
AU  - Jan Matysiak
AU  - Zbigniew Krasiński
AU  - Julia Frąckowiak
AU  - Anetta Hanć
AU  - Tomasz Urbanowicz
PY  - 2026
DA  - 2026/10/25
JO  - Nutrients
DO  - 10.3390/nu18213510
UR  - https://www.mdpi.com/2072-6643/18/21/3510
AB  - 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.
SN  - 2072-6643
ER  -