SGLT2 Inhibitors Associated With Small Rise in Hemoglobin and Hematocrit

Sodium-glucose cotransporter 2 (SGLT2) inhibitor use was associated with small but statistically significant increases in hemoglobin and hematocrit compared with control. The finding comes from a systematic review and meta-analysis of randomized clinical trials published in JAMA. The results were also presented at Kidney Week 2026 of the American Society of Nephrology.

The investigators noted that earlier trials had linked SGLT2 inhibitor use with higher hemoglobin and hematocrit compared with placebo, but how large and how important that association is remained unclear. The analysis also looked at markers of iron metabolism and erythropoiesis.

The researchers pooled 85 randomized, double-masked trials that compared SGLT2 inhibitors with placebo or active comparators. Together the trials included 70,543 participants with cardiovascular disease, diabetes, heart failure, and/or chronic kidney disease. Median trial duration was 24 weeks, and mean baseline hemoglobin was 13.6g/dL. Compared with control, SGLT2 inhibitor use was associated with a mean increase of 0.60g/dL in hemoglobin (95% CI, 0.55-0.66g/dL) and 2.36 percentage points in hematocrit.

Four of the 6 secondary outcomes showed significant associations: higher erythropoietin and red blood cell concentration, and lower ferritin and transferrin saturation. The analysis found no significant change in hepcidin or serum iron. According to the investigators, this pattern is compatible with stored iron being mobilized and used to support erythropoiesis. In the limitations they listed, heterogeneity was substantial and only partly explained by meta-regression, only 7.3% of participants had iron biomarker data, no patient-level analyses were performed, and the study did not report clinical outcomes.

The authors described the increases as small and of uncertain clinical significance. For comparison, they noted that erythropoiesis-stimulating agents raise hematocrit by about 5% to 11%. They also noted that further increases in people who already have elevated hemoglobin and hematocrit may be associated with higher rates of thromboembolic events, and that more study is needed.

Source: 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