SODIUM-GLUCOSE cotransporter 2 (SGLT2) inhibitors were associated with modest increases in haemoglobin and haematocrit levels in a meta-analysis of 85 randomised clinical trials, although the clinical significance of these changes remains unclear.
The findings provide a quantitative assessment of the association between SGLT2 inhibitors and markers of red blood cell production, iron metabolism, and erythropoiesis. The analysis included 70,543 participants with cardiovascular disease, diabetes, heart failure, or chronic kidney disease, with a median follow-up of 24 weeks.
Researchers searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to 22 July 2026. Eligible studies were randomised, double-masked clinical trials comparing SGLT2 inhibitors with placebo or active comparators. Three reviewers independently extracted the data, which were pooled using random-effects meta-analysis.
Of the 85 trials, 78 compared SGLT2 inhibitors with placebo, while seven used active comparators, most commonly sitagliptin.
The primary outcomes demonstrated statistically significant differences between treatment and control groups. Haemoglobin increased by 0.55 g/dL from baseline in participants receiving SGLT2 inhibitors, compared with a decrease of 0.08 g/dL in controls. The between-group difference was 0.60 g/dL (95% confidence interval [CI]: 0.55–0.66; p<0.001).
Haematocrit increased by 2.17% in the SGLT2 inhibitor group, while the control group experienced a change of −0.13%. The between-group difference was 2.36% (95% CI: 2.19–2.52; p<0.001).
Among the secondary outcomes, four of six demonstrated significant associations with SGLT2 inhibitor use. Erythropoietin (EPO) increased by 2.35 mIU/mL in the treatment group, compared with 0.04 mIU/mL in controls. The between-group difference was 2.11 mIU/mL (95% CI: 0.50–3.71; p=0.01). Transferrin saturation decreased by 2.2% with treatment, compared with 0.10% in controls, with a between-group difference of −0.84% (95% CI: −1.21 to −0.47; p<0.001).
The findings indicate that SGLT2 inhibitors are associated with changes in haemoglobin, haematocrit, EPO, and transferrin saturation. However, the magnitude and clinical implications of these effects remain uncertain.
Although the observed increases in haemoglobin and haematocrit were statistically significant, the analysis did not establish their clinical importance. Further investigation is needed to clarify the implications of these haematological changes for patients receiving SGLT2 inhibitor therapy.
Reference
Yang Y et al. Sodium-glucose cotransporter 2 inhibitor use and levels of hemoglobin, markers of iron metabolism, and erythropoiesis: a systematic review and meta-analysis of randomized clinical trials. JAMA. 2026; doi: 10.1001/jama.2026.19921.
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