Dapagliflozin for Anemia in Lower-Risk Myelodysplastic Syndromes

Overview

This study is a prospective, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of dapagliflozin in improving anemia in patients with lower-risk myelodysplastic syndromes (MDS). Anemia is the most common clinical problem in patients with lower-risk MDS and often leads to fatigue, reduced quality of life, and the need for repeated blood transfusions. Current treatment options, including erythropoiesis-stimulating agents and other therapies, are not effective in all patients, and additional treatment options are needed. Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that is widely used for the treatment of diabetes, heart failure, and chronic kidney disease. Previous studies have shown that SGLT2 inhibitors can increase hemoglobin levels, possibly by stimulating erythropoiesis. In this study, eligible patients will receive dapagliflozin 10 mg orally once daily for 24 weeks. The primary objective is to evaluate the hemoglobin response rate during the study period. Secondary objectives include changes in hemoglobin levels, transfusion requirements, and safety outcomes. This study aims to explore whether dapagliflozin can serve as a potential treatment option for anemia in patients with lower-risk MDS.

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis and cytopenias. Among these, anemia is the most common and clinically significant manifestation in patients with lower-risk MDS, often leading to fatigue, decreased quality of life, and increased transfusion requirements. Current treatment options for anemia in lower-risk MDS include erythropoiesis-stimulating agents (ESA) and other therapies such as luspatercept. However, these treatments are not universally effective, and access may be limited in certain settings. As a result, many patients remain transfusion-dependent or experience persistent anemia, highlighting the need for additional therapeutic options. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in the management of diabetes mellitus, heart failure, and chronic kidney disease. Multiple clinical studies have consistently demonstrated increases in hemoglobin and hematocrit levels in patients receiving SGLT2 inhibitors. The proposed mechanisms include increased erythropoietin production, modulation of iron metabolism, and reduction in plasma volume. These findings suggest a potential role of SGLT2 inhibitors in stimulating erythropoiesis. Recent observational data have suggested that SGLT2 inhibitor therapy may improve hemoglobin levels in patients with myeloid neoplasms, including MDS. However, these findings are limited by small sample sizes and retrospective study designs, and prospective clinical data are lacking. This study is designed as a prospective, single-arm, phase II clinical trial to evaluate the efficacy and safety of dapagliflozin in patients with lower-risk MDS and anemia. Participants will receive dapagliflozin 10 mg orally once daily for 24 weeks. The study will assess hemoglobin response, transfusion requirements, and safety outcomes over the study period. The results of this study are expected to provide proof-of-concept evidence for the use of SGLT2 inhibitors as a potential therapeutic option for anemia in patients with lower-risk MDS and to support further clinical development in this setting.