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. 2025 May 27.
doi: 10.1007/s00392-025-02685-6. Online ahead of print.

Erythropoietic response to oral iron with sodium-glucose co-transporter 2 inhibitors

Pedro Marques #  1   2   3 , Paula Matias #  4 , Christoforos K Travlos  5 , António Angélico-Gonçalves  6   7 , Hugo Diniz  8 , Francisco Vasques-Nóvoa  4   6 , Milton Packer  9   10 , Fernando Friões  4   11 , Michael A Tsoukas  12 , Thomas A Mavrakanas  5 , Abhinav Sharma #  13 , João Pedro Ferreira #  14   15
Affiliations

Erythropoietic response to oral iron with sodium-glucose co-transporter 2 inhibitors

Pedro Marques et al. Clin Res Cardiol. .

Abstract

Background: Anemia and iron deficiency are common in heart failure (HF) and chronic kidney disease (CKD). These conditions are associated with upregulation of hepcidin, which impairs the enteric absorption of iron, limiting the use of oral iron formulations in these populations. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are associated with enhanced erythropoiesis and have been shown to augment the erythropoietic response to intravenous iron. The effect of baseline SGLT2i therapy in the erythropoietic response following oral iron supplementation is currently not known.

Objectives: To compare the erythropoietic response to oral iron supplementation in patients with HF or CKD, using and not using SGLT2i as background therapy.

Methods: This is a retrospective analysis of ambulatory patients with HF or CKD followed in cardio-kidney-metabolic clinics from a quaternary care hospital in Canada and a tertiary care hospital from Portugal. An age- and sex-matched population of patients using (n = 76) and not using (n = 76) a SGLT2i was compared for changes in hemoglobin and hematocrit following oral iron supplementation. Secondary outcomes included changes in iron biomarkers, natriuretic peptides and kidney function.

Results: Overall, the mean age was 75 ± 9 years, 49% were men, 119 (78%) had CKD, 107 (70%) HF, and 113 (74%) had anemia. After adjustment for baseline differences, SGLT2i users experienced a greater increase in hemoglobin and hematocrit compared to SGLT2i non-users: hemoglobin + 0.80 g/dL (95% confidence interval [CI] 0.39-1.21 g/dL, p < 0.001); hematocrit + 3.0% (95% CI 1.0-4.0%, p < 0.001). No significant differences on iron biomarkers or any of the secondary outcomes were found between the groups.

Conclusions: Oral iron supplementation in patients with background therapy including a SGLT2i (vs. SGLT2i non-users) was associated with a greater increase in hemoglobin and hematocrit. These results suggest that patients with HF or CKD patients treated with SGLT2i might have an enhanced erythropoietic response to oral iron supplementation.

Keywords: Anemia; Chronic kidney disease; Heart failure; Iron deficiency; Oral iron; SGLT2i.

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Conflict of interest statement

Declarations. Conflict of interest: PM received salary support from an educational grant by Janssen. MP reports consulting fees from 89Bio, Abbvie, Altimmune, Amgen, Ardelyx, AstraZeneca, Boehringer-Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Lilly, Moderna, Novartis, Reata, Regeneron, Relypsa and Salamandra. MAT reports personal fees from Boehringer-Ingelheim, AstraZeneca, Janssen, Novo-Nordisk and Eli Lilly, outside the submitted work. TAM received speaker honoraria from Daiichi Sankyo, BMS Canada, Janssen, Astra Zeneca, and Pfizer and has served on advisory boards for Böhringer Ingelheim, Bayer, GSK, and Servier outside the submitted work. He has also received an unrestricted research grant from Astra Zeneca and operational grants from the Kidney Foundation of Canada, the Heart & Stroke foundation of Canada and the Canadian Institute of Health Research. He is receiving salary support from the Fonds de Recherche Quebec Santé (Junior 1 Clinician Scholar Award # 298742) and is supported by a KRESCENT New Investigator Award. AS has received support from the Fonds de Recherche Santé Quebec (FRSQ) Junior 1 clinician scholars’ program, Canadian Institute of Health Research (Grant #175095), Roche Diagnostics, Boehringer-Ingelheim, Novartis, Janssen, Novo-Nordisk, Servier, AstraZeneca, and Takeda. JPF has received research support from Boehringer-Ingelheim, AstraZeneca and Novartis, through his institution, the University of Porto. The reminder authors report not having relevant conflicts of interest regarding the content of this manuscript.

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