Incidental changes in hemoglobin levels in patients with myelofibrosis receiving treatment with sodium-glucose co-transporter-2 inhibitors

Incidental changes in hemoglobin levels in patients with myelofibrosis receiving treatment with sodium-glucose co-transporter-2 inhibitorsSodium-glucose co-transporter-2 inhibitors (SGLT-2I) (also known as gliflozins or flozins) are increasingly prescribed for diabetes mellitus, heart failure and chronic kidney disease. 1 Food and Drug Administration (FDA)-approved drugs within the SGLT-2I class, bexagliflozin, canagliflozin, dapagliflozin, empagliflozin, ertugloflozin, and sotagliflozin offer cardioprotection and enhance erythropoiesis through inter-related mechanisms. 2 The physiology of SGLT2-I-induced erythrocytosis is multifactorial; potential mechanisms include: i) increased erythropoietin (Epo) production; ii) suppression of hepcidin and modulation of iron metabolism; and iii) hemoconcentration. 3In placebo-controlled studies, empagliflozin demonstrated a dose-dependent increase in hemoglobin (Hb) and hematocrit (Hct) levels, with a median increase in Hct of 4.85.5% and 5.05.3% with empagliflozin 10 mg and 25 mg, respectively, versus 0.94.7% with placebo. 4SGLT-2I have also been shown to ameliorate anemia in patients with chronic kidney disease; in a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) 5 and Dapagliflozin in Patients with Chronic Kidney Disease (DAPA-CKD) trials, 6 increase in Hct was 2.4% and 2.3% higher in the canagliflozin and dapagliflozin arms, respectively, compared to placebo.Moreover, resolution of anemia was noted in a higher proportion of patients on dapagliflozin than placebo (53.3% vs. 29.4%).In the light of these observations, we postulate that SGLT-2I might stimulate erythropoiesis and improve anemia in chronic myeloid malignancies such as myelofibrosis (MF). [7][8]][9] Accordingly, in the current study, our primary objective was to evaluate the impact of SGLT-2I therapy on Hb levels and anemia-related outcomes in patients with MF.After approval by the Institutional Review Board for minimal risk research protocol, the Mayo Clinic myeloproliferative neoplasm (MPN) clinical database was queried to identify patients with primary or secondary MF, prescribed SGLT2-I for diabetes mellitus, heart failure or chronic kidney disease, following established diagnosis of MF. 10 The time of SGLT-2I initiation was considered as baseline and for each patient, baseline Hb, changes in Hb, and thrombotic events during SGLT-2I treatment were recorded.Therapeutic interventions for MF including timing of initiation and discontinuation of cytoreductive agents were carefully documented.A total of 16 patients with MF (primary MF [PMF], N=12; post-essential thrombocythemia MF [post-ET MF], N=4) received treatment with empagliflozin (N=10), dapagliflozin (N=4), or canagliflozin (N=2) between July 2019 and March 2024.Median age was 74 years; 56% were males.JAK2V617F mutation was