Efficacy of Dapagliflozin in Anemic patients with Heart failure: A Systematic review and Meta-Analysis

Background: Anemia is a common comorbidity in patients with heart failure and is strongly associated with adverse clinical outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, specifically dapagliflozin, may improve anemia-related biomarkers. However, findings from individual trials have been inconsistent, leaving the magnitude and consistency of these effects unclear. Objective: Our study aims to clarify the effects of dapagliflozin on anemia in patients with heart failure. Methods: We conducted a systematic search of PubMed, Embase, Cochrane CENTRAL, and trial registries for randomized and non-randomized clinical trials. Outcomes included changes in hemoglobin, ferritin, transferrin saturation (TSAT), and serum iron. Mean differences (MD) and 95% confidence intervals (CIs) were pooled using random-effects models. We performed sensitivity analyses by sequentially excluding studies and assessed bias using Cochrane tools and ROBINS-I, grading evidence via GRADE. Results: Six studies (n=5,075) were included. Dapagliflozin significantly increased hemoglobin (MD 1.05; 95% CI 0.75–1.35; P < 0.00001). Ferritin was significantly reduced (MD –14.50; 95% CI –22.13 to –6.86; P = 0.0002); sensitivity analyses excluding Bhaganagarapu et al. amplified this reduction (MD –23.37; 95% CI –34.57 to –12.17; P < 0.00001). While TSAT changes were non-significant overall (MD 0.37), sensitivity analysis demonstrated a significant reduction (MD –1.36; 95% CI –2.37 to –0.35). Serum iron remained unchanged (MD –0.09). Evidence certainty was moderate-to-high for hemoglobin and ferritin but low for TSAT and serum iron. Conclusion: In heart failure patients, dapagliflozin reliably increases hemoglobin and decreases ferritin. While the primary analyses for transferrin saturation were non-significant, sensitivity testing revealed significant changes. These findings suggest that dapagliflozin may beneficially influence iron metabolism. However, further large-scale, dedicated trials are warranted to confirm these mechanisms.