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Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Anemia in Patients with Chronic Kidney Disease: A Pre-Post
Selena Gajić1, Filip Simović2, Ana Bontić1,2
1Clinic of Nephrology, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.
Insights
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) showed modest hemoglobin increases in chronic kidney disease (CKD) patients over 18 months. Real-world data indicated stable iron status and no significant differences between empagliflozin and dapagliflozin.
Area of Science:
- Nephrology
- Pharmacology
- Hematology
Background:
- Anemia is a common complication in chronic kidney disease (CKD), worsening quality of life and cardiovascular risk.
- Sodium-glucose cotransporter-2 inhibitors (SGLT2is) offer renal and cardiovascular benefits, with some evidence of improving hematologic parameters.
- Limited real-world data exist on the long-term effects of SGLT2is on hemoglobin and iron metabolism in CKD patients.
Purpose of the Study:
- To evaluate the longitudinal effects of SGLT2is on hemoglobin and iron metabolism in adult patients with CKD stages 1-4.
- To compare the effects of empagliflozin and dapagliflozin on hematologic parameters over 18 months.
- To identify factors influencing hematologic trajectories during SGLT2i treatment in CKD.
Main Methods:
- A pre-post analysis of 118 CKD patients treated with empagliflozin or dapagliflozin (10 mg daily) for 18 months.
- Assessment of hemoglobin, ferritin, C-reactive protein, albumin, proteinuria, and eGFR at baseline and 18 months.
- Statistical analysis using repeated-measures general linear models, with ferritin adjusted for inflammatory and nutritional status.
Main Results:
- Unadjusted hemoglobin showed a modest increase (136.5 to 138.8 g/L, p=0.028), while unadjusted ferritin decreased (102.2 to 89.9 µg/L, p=0.011).
- Adjusted ferritin levels remained unchanged (p=0.752), and no significant longitudinal effects on Hb or ferritin were found over time.
- Baseline eGFR, proteinuria, sex, and baseline ferritin significantly influenced hematologic outcomes.
Conclusions:
- SGLT2i therapy in CKD patients was associated with modest hemoglobin increases but did not significantly alter adjusted ferritin levels over 18 months.
- No significant differences in longitudinal Hb or ferritin trajectories were observed between empagliflozin and dapagliflozin.
- Baseline kidney function, proteinuria, iron status, and sex are key determinants of hematologic response to SGLT2is in CKD.
Abstract:
Background and Objectives: Anemia is a common complication of chronic kidney disease (CKD) and is associated with reduced quality of life, accelerated disease progression, and increased cardiovascular risk. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated significant renal and cardiovascular benefits, and clinical trials have reported improvements in hematologic parameters during treatment. However, real-world evidence regarding their longitudinal effects on hemoglobin (Hb) and iron metabolism in patients with CKD remains limited. Materials and Methods: We conducted a pre-post analysis of 118 adult patients with CKD stages 1-4 treated with SGLT2is (empagliflozin or dapagliflozin) at the University Clinical Center of Serbia between January 2024 and June 2025. Patients received either agent at 10 mg once daily for 18 months. Hb, ferritin, C-reactive protein (CRP), albumin (Alb), daily proteinuria (Prt), and estimated glomerular filtration rate (eGFR) were assessed at baseline and at 18 months. Ferritin was adjusted for inflammatory and nutritional status using a residualization model incorporating CRP and Alb. Changes between the two time points were analyzed using repeated-measures general linear models (GLMs). Results: In unadjusted analyses, mean Hb increased modestly from 136.5 ± 17.9 g/L at baseline to 138.8 ± 18.9 g/L at follow-up (p = 0.028), while median ferritin decreased from 102.2 µg/L to 89.9 µg/L (p = 0.011). After adjustment for CRP and Alb, ferritin levels remained unchanged (p = 0.752). Repeated-measures analyses showed no significant longitudinal effect of time on Hb or ferritin and no significant interaction between time and SGLT2i type. Baseline eGFR, Prt, sex, and baseline ferritin significantly influenced longitudinal hematologic trajectories. Conclusions: SGLT2i therapy was associated with modest increases in Hb levels over 18 months, while inflammatory status remained stable and no significant reduction in ferritin levels was observed after adjustment for inflammatory and nutritional factors. Longitudinal Hb and ferritin trajectories did not differ significantly between empagliflozin and dapagliflozin, while baseline kidney function, Prt, iron status, and sex significantly influenced hematologic outcomes. Although causal inference is limited by the absence of a control group, these findings suggest a possible favorable effect of SGLT2is on anemia-related parameters in patients with CKD.
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