Polycythemia due to SGLT-2 inhibitors: who is at risk?

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are oral antidiabetic agents that have been increasingly used in recent years. One of their lesser-known adverse effects is polycythemia (erythrocytosis), for which data remain limited. In this study, we aimed to investigate the incidence of erythrocytosis associated with SGLT-2 inhibitor use and the risk factors influencing these changes.

All patients who initiated SGLT-2 inhibitor therapy in our clinic between January 2020 and January 2021 were retrospectively evaluated. Hb and Hct levels were monitored for a median of 16 months following treatment initiation.

Polycythemia developed in 15.1% (n = 58) of the 385 patients included in the study. Male sex and smoking were identified as significant risk factors for erythrocytosis, whereas insulin use and iron deficiency were found to be protective factors. The mean increase in hemoglobin levels among all patients was 0.97 ± 0.94 g/dL. A negative correlation was observed between baseline Hb levels and the degree of Hb increase associated with SGLT-2 inhibitor use. Patients who were excluded from the study due to baseline polycythemia (n = 18) were evaluated separately, and no significant change in their Hb levels was detected during follow-up.

SGLT-2 inhibitors significantly increase Hb and Hct levels in all patients without polycythemia. In anemic individuals, SGLT-2 inhibitors appear to induce greater increases in Hb and Hct, suggesting a potential additional hematologic benefit in this subgroup. Moreover, SGLT-2 inhibitors have been shown to be safe in patients with pre-existing polycythemia.