People with chronic kidney disease and heart failure frequently develop anemia, a condition characterized by low hemoglobin levels and reduced oxygen transport throughout the body. Previous clinical trials had already shown that patients receiving SGLT2 inhibitors experienced increases in hemoglobin and hematocrit, but the magnitude and underlying mechanisms of these changes remained unclear.
To better understand these effects, Eisenga and colleagues performed a systematic review and meta-analysis of 85 randomized clinical trials, including 70,543 participants with diabetes, cardiovascular disease, heart failure, and chronic kidney disease. Compared with placebo or other glucose-lowering medications, SGLT2 inhibitors were consistently associated with higher hemoglobin and hematocrit levels after a median follow-up of 24 weeks. The increase was modest but remarkably consistent across studies. On average, hemoglobin levels increased by 0.60 g/dL and hematocrit by 2.36% compared with control groups.
The researchers also investigated markers involved in iron metabolism and red blood cell production. Patients receiving SGLT2 inhibitors showed higher erythropoietin (EPO) concentrations, the hormone that stimulates red blood cell production in the bone marrow. At the same time, transferrin saturation and ferritin levels decreased, while serum iron remained largely unchanged. These findings suggest that the body mobilizes iron stores to support increased red blood cell production.
Although the results provide important insights into how SGLT2 inhibitors affect blood and iron parameters, the clinical significance of these changes remains uncertain. The increases in hemoglobin and hematocrit were relatively small, and it is not yet clear whether they contribute directly to the cardiovascular and kidney benefits observed with these drugs. The findings do, however, offer new clues about the biological effects of SGLT2 inhibitors. Further studies are needed to determine whether changes in red blood cell production and iron metabolism play a direct role in the benefits of SGLT2 inhibitor therapy.
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