Impact of Sodium-glucose Co-transporter 2 Inhibitors on Bone Mineral Biomarkers and Renal Progression in Diabetic Kidney Disease: A Prospective Observational Study

Background: Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus. Although the renometabolic benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors are well established, their effects on bone mineral metabolism in DKD remain underexplored. This study prospectively evaluated changes in key bone-related biomarkers among DKD patients receiving SGLT2 inhibitors. Materials and Methods: In this prospective, open-label, hospital-based case–control study, 50 patients with type 2 diabetes and DKD (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m 2 ) were enrolled. Forty patients received SGLT2 inhibitors (empagliflozin or dapagliflozin), and ten continued standard therapy. Baseline and 3-month assessments included glycemic indices, renal function, and bone mineral parameters – serum calcium, phosphorus, 25-hydroxy Vitamin D [25(OH) D], intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and bone mineral density (BMD). Results: SGLT2 inhibitor therapy significantly reduced body weight, body mass index, urinary albumin-to-creatinine ratio, and eGFR. It was associated with significant increases in iPTH and FGF23, without significant changes in serum calcium, 25(OH) D, or BMD. Dapagliflozin produced a greater reduction in serum uric acid than empagliflozin ( P = 0.04). Conclusion: SGLT2 inhibitor therapy in DKD was associated with favorable metabolic and renal effects along with hormonal alterations involving iPTH and FGF23, suggesting possible modulation of phosphate handling. These short-term findings likely reflect adaptive biochemical changes, but long-term studies are needed to determine their clinical relevance and implications for skeletal health and monitoring strategies during therapy.