SGLT2 Inhibitors: Dual Effects on Erythropoiesis and Bone Metabolism.

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been used as a therapy for type 2 diabetes mellitus, heart failure, and chronic kidney disease (CKD); however, their effects on erythropoiesis, phosphate regulation, and bone turnover are incompletely clarified. Studies report a marked increase in hemoglobin and hematocrit during treatment, suggesting an erythropoietic response rather than simple hemoconcentration. Simultaneously, changes in mineral metabolism, including a modest increase in phosphate, fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), raise questions about the possible consequences for bone quality, mainly in individuals with diabetes or CKD who are at increased risk of fracture. Accordingly, this narrative review was structured through a literature search of PubMed, Scopus and Google Scholar for studies published in English up to November 2025. Keywords included SGLT2 inhibitors, erythropoiesis, bone metabolism, phosphate homeostasis, FGF-23, PTH, vitamin D, bone mineral density (BMD) and fracture. Randomized trials, mechanistic studies, animal experiments, observational cohorts, sub-analysis and reviews were included. Current evidence shows that SGLT2 inhibition promotes erythropoietin production, enhances iron mobilization and modifies the bone marrow environment, while also influencing the FGF- 23-PTH-vitamin D axis through renal phosphate handling. Although canagliflozin has been associated with reduction in hip BMD and possible fracture risk, findings from the drug class remain inconsistent and are often confounded by baseline comorbidities. In conclusion, SGLT2 inhibitors trigger a connected hematologic and mineral changes, but their long-term skeletal impact remains uncertain. Further mechanistic and longitudinal studies are advised to clarify these outcomes.