The Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Hemoglobin Levels in Patients with CKD

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Background: Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2is) confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to assess the effect of SGLT2is on hemoglobin levels in CKD patients. Methods: We conducted a retrospective study in patients seen in a community nephrology practice with eGFR 25-90 ml/min per 1.73 m2 who received either dapagliflozin 10 mg daily or empagliflozin 10 mg daily between 1/2022 and 9/2023. The primary outcome was the mean difference in hemoglobin levels 8 months prior and 8 months post initiation of SGLT2i therapy. Results: Among 402 patients screened from 1/2022 to 9/2023, 72 were prescribed either dapagliflozin 10 mg daily or empagliflozin 10 mg daily, with a mean eGFR of 51.2 ml/min/1.73 m2. Of those 72 patients, 46 (63.88%) were male and 26 (36.11%) female. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 8 months before initiating SGLT2i therapy was 12.8 g/dL, with a mean drop of 0.13 g/dL (95% CI, -0.32 to +0.06) in 8 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.06 g/dL (95% CI, 0.88 to 1.25). Overall, we observed a mean hemoglobin difference of 1.19 g/dL (95% CI, 0.88 to 1.5, p < 0.001) before and after initiating SGLT2i therapy. (Figure 1) Conclusions: The use of either dapagliflozin or empagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Larger prospective trials can help better understand the size of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure hospitalization risk.

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