SGLT2 Inhibitors Linked to Modest Increases in Hemoglobin and Hematocrit: Study
Treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors was associated with modest but statistically significant increases in hemoglobin and hematocrit levels across diverse patient populations, according to a systematic review and meta-analysis. These changes may reflect increased red blood cell production and altered fluid balance, highlighting the importance of monitoring hematological parameters during treatment. The study was published in JAMA by Yaqin Yang and colleagues.
For quantifying the exact amount of the change in red blood cell parameters, erythropoietin secretion, and iron metabolism biomarkers, a systematic search was conducted in PubMed, Web of Science, and CENTRAL from the beginning of their existence up to July 22, 2026. The meta-analysis included 85 randomized and double-masked clinical trials (median study duration was 24 weeks, interquartile range was 12-32 weeks) involving 70,543 adult patients (average age was 62.4 ± 9.4 years; 25,334 women [35.9%]) who had cardiovascular disease, diabetes, heart failure, and/or chronic kidney disease.
The average value of hemoglobin at baseline was 13.6 ± 1.5 g/dL, and the average value of hematocrit at baseline was 41.5% ± 4.9%. In total, 78 trials (67,208 subjects) tested SGLT2 inhibitors against placebo, whereas 7 trials (3,335 subjects) included active comparator treatment, mainly sitagliptin.
Key findings:
- The data synthesis for the 85 randomized trials, involving 70,543 participants, yielded remarkably consistent elevations in hematologic parameters.
- The hemoglobin was increased by 0.55 g/dL (95% CI, 0.49-0.61 g/dL; P < 0.001) in the SGLT2 inhibitor cohort versus −0.08 g/dL (95% CI, −0.13 to −0.03 g/dL; P = 0.003) in the control cohort, for an overall significant difference of 0.60 g/dL (95% CI, 0.55 to 0.66 g/dL; P < 0.001).
- Hematocrit was found to increase by 2.17% (95% CI, 1.95%-2.39%; P < 0.001) in the SGLT2 inhibitor group versus −0.13% (95% CI, −0.28% to 0.01%; P = 0.07) in the control group, for an overall significant difference of 2.36% (95% CI, 2.19%-2.52%; P < 0.001).
- Of the six secondary endpoints examined, four showed statistically significant correlations, namely, an elevation in serum erythropoietin (2.35 mIU/mL in the SGLT2 inhibitor group versus 0.04 mIU/mL in the control group; difference 2.11 mIU/mL [95% CI, 0.50-3.71 mIU/mL]; P = 0.01), and decrease in transferrin saturation (−2.2% in the SGLT2 inhibitor group versus −0.10% in the control group; difference −0.84% [95% CI, −1.21% to −0.47%]; P < 0.001).
In summary, pooled results from 85 RCTs show that treatment with SGLT2 inhibitors causes small but statistically significant increases in hemoglobin, hematocrit, and erythropoietin concentrations. This study's findings clearly illustrate the need for further research on the clinical importance of such changes in these red blood cell parameters.
Reference:
Yang Y, Yang C, Wang 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. Published online October 24, 2026. doi:10.1001/jama.2026.19921
