Abstract and Introduction
Abstract
Purpose of Review: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a relatively new class of oral glucose-lowering agents that reduce adverse cardiovascular and kidney outcomes among individuals with chronic kidney disease (CKD). Emerging evidence suggests that SGLT2i may also affect bone and mineral metabolism. This review analyzes recent evidence on the safety of SGLT2i with respect to bone and mineral metabolism in people with CKD, and discusses potential underlying mechanisms and clinical implications.
Recent Findings: Recent studies have documented the beneficial effects of SGLT2i on cardiovascular and renal outcomes among individuals with CKD. SGLT2i may alter renal tubular phosphate reabsorption and are associated with increased serum concentrations of phosphate, fibroblast growth factor-23 (FGF-23), parathyroid hormone (PTH), decreased 1,25-hydroxyvitamin D levels, as well as increased bone turnover. Clinical trials have not demonstrated an increased risk of bone fracture associated with SGLT2i use among patients with CKD with or without diabetes mellitus.
Summary: Although SGLT2i are associated with abnormalities of bone and mineral metabolism, they have not been linked to a higher risk of fracture among patients with CKD. More research is needed on the association between SGLT2i and fracture risk in this population.
Introduction
Chronic kidney disease (CKD) is common in the US; indeed, an estimated 37 million American adults live with CKD.[1] Individuals with CKD have disproportionately high rates of cardiovascular disease, progression to end-stage kidney disease requiring renal replacement therapy, and death.[2–5] Additionally, CKD is frequently associated with disorders of bone and mineral metabolism including abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; as well as abnormalities in bone mineralization, turnover, volume, linear growth, and strength.[6]
In recent randomized controlled clinical trials, medications within the sodium-glucose cotransporter (SGLT) 2 inhibitors (SGLT2i) class have shown improvements in adverse cardiovascular and kidney outcomes among individuals with CKD.[7–10] For instance, in the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, canagliflozin was associated with a reduction in the risks of kidney failure and cardiovascular events among participants with type 2 diabetes and CKD.[8] Likewise, in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial, the SGLT2i dapagliflozin demonstrated similar results among individuals with CKD, regardless of the presence of diabetes mellitus.[9] With respect to safety, common adverse effects of SGLT2i include diabetic ketoacidosis, volume depletion, and genital and urinary tract infections.[8–10] Extant data suggest that SGLT2i may affect bone and mineral metabolism via alterations in renal phosphate reabsorption, increased calcium excretion, as well as increased bone turnover and decreased bone mineral density (BMD). In this review, we discuss recent evidence on the safety of SGLT2i with respect to bone and mineral metabolism in people with CKD. Furthermore, potential underlying mechanisms and clinical implications are reviewed.[]
Curr Opin Nephrol Hypertens. 2023;32(4):324-329. © 2023 Lippincott Williams & Wilkins
