Sodium–glucose cotransporter 2 (SGLT2) inhibitors provide metabolic and cardiorenal benefits for patients with type 2 diabetes but are associated with a number of safety issues. Here, we discuss evidence suggesting that indirect activation of the FGF23–1,25-dihydroxyvitamin D–parathyroid hormone axis by SGLT2 inhibition might contribute to adverse effects on bone health.
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DeFronzo, R. A., Norton, L. & Abdul-Ghani, M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat. Rev. Nephrol. 13, 11–26 (2017).
Kohan, D. E., Fioretto, P., Tang, W. & List, J. F. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 85, 962–971 (2014).
Bilezikian, J. P. et al. Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J. Clin. Endocrinol. Metab. 101, 44–51 (2016).
Watts, N. B. et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 101, 157–166 (2016).
Blau, J. E. et al. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight 3, 99123 (2018).
Pitts, R. F. & Alexander, R. S. The renal reabsorptive mechanism for inorganic phosphate in normal and acidotic dogs. Am. J. Physiol. 142, 648–662 (1944).
J.E.B. is supported by funding from the Intramural Research Program of the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). S.I.T. acknowledges funding from the NIDDK (grant number P30DK072488).
J.E.B. declares no competing interests. S.I.T. is a consultant for Ionis Pharmaceuticals, has research support provided to the University of Maryland School of Medicine by Regeneron Pharmaceuticals and has ownership of stock in Celgene, Amgen and Abbott Laboratories.
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Blau, J.E., Taylor, S.I. Adverse effects of SGLT2 inhibitors on bone health. Nat Rev Nephrol 14, 473–474 (2018). https://doi.org/10.1038/s41581-018-0028-0
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