Dapagliflozin effect on anemia outcomes in patients with diabetes and CKD

Abstract Background Anemia is a prevalent complication in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), contributing to adverse clinical outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), including dapagliflozin, have demonstrated cardiovascular and renal benefits, with emerging evidence suggesting their role in erythropoiesis and anemia correction. Methods This was a prospective cohort study, including patients with T2DM and CKD (stages 3–4). Patients were classified into dapagliflozin and control groups, with further stratification based on baseline anemia status. Outcomes included incident anemia, hemoglobin increase, anemia correction, development of iron deficiency anemia (IDA), and erythropoiesis-stimulating agent (ESA) therapy initiation over a 12-month follow-up. Results A total of 255 patients (dapagliflozin: n = 155; control: n = 100) were included, with baseline anemia present in 109 dapagliflozin-treated and 66 control patients. IDA development was higher in dapagliflozin-treated patients (36.7% vs. 18.2%, p = 0.005), occurring exclusively in patients with baseline anemia and more frequently among females. Among non-anemic patients, incident anemia was observed in 11.8% of controls but none in the dapagliflozin group. In anemic patients, a hemoglobin increase ≥ 1 g/dL was more frequent in the dapagliflozin group (66.7% vs. 14.3%, p < 0.001), with a significantly shorter time to response (7.30 vs. 11.57 months, p < 0.001). Anemia correction—defined as achieving hemoglobin ≥ 13.0 g/dL in males or ≥ 12.0 g/dL in females, with a ≥ 1 g/dL increase—was achieved in 53.6% of dapagliflozin-treated patients versus 4.8% of controls ( p < 0.001). These findings were consistent in the propensity score-matched cohort, reinforcing the robustness of the observed associations. ESA initiation was lower in the dapagliflozin group (7.3% vs. 24.2%, p = 0.002), with a longer time to therapy initiation. Conclusions Dapagliflozin was associated with significant improvements in hemoglobin levels and anemia correction in patients with T2DM and CKD. However, an increased risk of IDA, particularly in female patients, warrants careful monitoring. The protective effects of dapagliflozin against ESA initiation highlight its potential role in anemia management. However, due to the observational design, causality cannot be definitively inferred.