Large meta-analysis sheds new light on how SGLT2 inhibitors affect blood and iron parameters

Research led by internist-nephrologist Dr. Michele Eisenga shows that SGLT2 inhibitors, a class of drugs widely used to treat type 2 diabetes, heart failure and chronic kidney disease, consistently increase hemoglobin and hematocrit levels.

By combining data from 85 randomized clinical trials involving more than 70,000 participants, the researchers found that these drugs consistently increase hemoglobin and hematocrit levels and may influence the way the body regulates iron and produces red blood cells. The study is published in the JAMA.

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.

Largest overview to date

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 consistent across studies. On average, hemoglobin levels increased by 0.60 g/dL and hematocrit by 2.36% compared with control groups.

Effects on iron metabolism

The researchers also investigated markers involved in iron metabolism and red blood cell production. Patients receiving SGLT2 inhibitors showed higher concentrations of erythropoietin (EPO), 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.

Clinical implications remain uncertain

Although the results provide 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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Gaby Clark

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Robert Egan

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