Effect of SGLT2 inhibitors on hemoglobin and hematocrit levels in Heart failure: a systematic review and meta-analysis

Abstract Aim The aim of this study is to evaluate the effects of Sodium-glucose cotransporter-2 (SGLT2) inhibitors on hemoglobin (Hb) and hematocrit (Hct) levels in patients with heart failure (HF). Methods We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials (RCTs) until April 2025. Changes in Hb and Hct were evaluated in HF patients treated with SGLT2 inhibitors compared to control subjects. A random-effects model was applied to calculate mean differences (MDs) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed across different SGLT2 inhibitors, follow-up durations, and types of control groups. Between-study heterogeneity was quantified using the I² statistic, and meta-regression analyses were performed to explore the influence of baseline clinical characteristics on hematologic responses. Publication bias was evaluated using funnel plots and Egger’s test. Results Seventeen randomized controlled trials (RCTs) with 16,784 participants (mean age 68.65 years, 65.56% male) were included. SGLT2 inhibitors significantly increased Hb (MD = 0.68 g/dL, 95% CI: 0.53; 0.83, I² = 39.7%, p-value 0.0001) and Hct (MD = 2.15%, 95% CI: 1.73; 2.57, I² = 66.6%, p-value 0.0001) compared to controls. Subgroup analyses showed consistent benefits across individual SGLT2 inhibitors, duration of follow-up (≥6 months vs 6 months), and comparator type (placebo vs active control). There was no evidence of publication bias. Conclusion SGLT2 inhibitors significantly increase levels of Hb and Hct in patients with HF. Further research is warranted to assess clinical significance in relation to Hb and Hct changes in patients with pre-existing anemia or renal dysfunction.