Adverse effects of SGLT2 inhibitors on bone health

Nature Reviews Nephrology volume 14, pages473–474(2018)Cite this article

Subjects

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

Rent or Buy

All prices are NET prices.

Fig. 1: Time course of pharmacodynamic responses to canagliflozin treatment.

References

  1. 1.

    DeFronzo, R. A., Norton, L. & Abdul-Ghani, M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat. Rev. Nephrol. 13, 11–26 (2017).

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    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).

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    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).

    Article  PubMed  CAS  Google Scholar 

  4. 4.

    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).

    Article  PubMed  CAS  Google Scholar 

  5. 5.

    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).

    Article  PubMed  Google Scholar 

  6. 6.

    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).

    CAS  Google Scholar 

Download references

Acknowledgements

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).

Author information

Affiliations

  1. Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Jenny E. Blau

  2. Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Simeon I. Taylor

Authors
  1. Jenny E. Blau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simeon I. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simeon I. Taylor.

Ethics declarations

Competing interests

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing