Sodium-Glucose Cotransporter 2 Inhibitor Use and Levels of Hemoglobin, Markers of Iron Metabolism, and Erythropoiesis
Yaqin Yang, Changyuan Yang, Yanmei Wang, Pien Rawee, Aleix Cases, David E. Leaf, Lucia del Vecchio, Taulant Muka, Hiddo J. L. Heerspink, Ron T. Gansevoort, Michele F. EisengaImportance
In randomized clinical trials, sodium-glucose cotransporter 2 (SGLT2) inhibitor use was associated with increased hemoglobin and hematocrit compared with placebo. However, the magnitude and importance of this association remain unclear.
Objective
To evaluate the associations between SGLT2 inhibitor use and levels of hemoglobin, hematocrit, and markers of iron metabolism and erythropoiesis compared with placebo or active comparator.
Data Sources
PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to July 22, 2026.
Study Selection
Randomized, double-masked clinical trials comparing SGLT2 inhibitor use with placebo or active comparators in patients with 1 or more of the following conditions: cardiovascular disease, diabetes, heart failure, and chronic kidney disease.
Data Extraction and Synthesis
Three reviewers independently extracted data and results were pooled using random-effects meta-analysis.
Main Outcomes and Measures
Primary outcomes were changes in hemoglobin and hematocrit. Secondary outcomes were changes in red blood cell concentration, erythropoietin (EPO), and iron measures (serum iron, ferritin, transferrin saturation, and hepcidin).
Results
A total of 85 randomized clinical trials were analyzed (median [IQR] duration, 24 [12-32] weeks), including 70 543 participants (mean [SD] age, 62.4 [9.4] years; 25 334 female [35.9%]). Mean (SD) baseline hemoglobin was 13.6 (1.5) g/dL; baseline hematocrit was 41.5% (4.9). Seventy-eight clinical trials (67 208 participants) compared SGLT2 inhibitors with placebo, and 7 clinical trials (3335 participants) used active comparators, most commonly sitagliptin (2 trials [1158 participants]). From baseline to follow-up, hemoglobin changed by 0.55 g/dL (95% CI, 0.49 to 0.61 g/dL;
Conclusions and Relevance
In a meta-analysis of randomized clinical trials, compared with control, SGLT2 inhibitor use was associated with small statistically significant increases in hemoglobin and hematocrit levels. The clinical significance of these findings is unclear.