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

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.