Skip to main content

Advertisement

SpringerLink
Log in

Long-term efficacy of empagliflozin as an add-on treatment for chronic SIAD: a case report and literature review

  • Rapid Communication
  • Published:
Hormones Aims and scope Submit manuscript

Abstract

Background

SLGT-2 inhibitors have recently been investigated as a promising therapy for syndrome of inappropriate antidiuresis (SIAD). However, to our knowledge, no report has been published about their use for this indication in the long term.

Case presentation

We report the case of a 68-year-old male with type 2 diabetes and chronic SIAD, in whom serum sodium levels were not adequately controlled by urea monotherapy. Other treatment options were not viable due to inefficacy or adverse effects. The initiation of empagliflozin, in addition to urea, led to the full normalization of serum sodium. Reduction and subsequent discontinuation of urea were attempted upon patient request, but this resulted in a relapse of hyponatremia. Nevertheless, stable normonatremia was again achieved and maintained for more than 6 months after re-establishing a combination therapy with empagliflozin and urea.

Conclusions

SGLT2 inhibitors might represent an effective treatment for SIAD, even in the long term. Specific clinical trials are needed to confirm this result.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Data Availability

No additional data were generated apart from those presented in the manuscript.

References

  1. Ellison DH, Berl T (2007) The syndrome of inappropriate antidiuresis. N Engl J Med 356:2064–2072. https://doi.org/10.1056/NEJMcp066837

    Article  CAS  PubMed  Google Scholar 

  2. Verbalis JG, Goldsmith SR, Greenberg A et al (2013) Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med 126:S1-42. https://doi.org/10.1016/j.amjmed.2013.07.006

    Article  PubMed  Google Scholar 

  3. Spasovski G, Vanholder R, Allolio B et al (2014) Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 170:G1-47. https://doi.org/10.1530/EJE-13-1020

    Article  CAS  PubMed  Google Scholar 

  4. Winzeler B, Lengsfeld S, Nigro N et al (2016) Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis. J Intern Med 280:609–617. https://doi.org/10.1111/joim.12532

    Article  CAS  PubMed  Google Scholar 

  5. Lockett J, Berkman KE, Dimeski G et al (2019) Urea treatment in fluid restriction-refractory hyponatraemia. Clin Endocrinol (Oxf) 90:630–636. https://doi.org/10.1111/cen.13930

    Article  CAS  PubMed  Google Scholar 

  6. Bhandari S, Peri A, Cranston I et al (2017) A systematic review of known interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia and a meta-analysis of the vaptans. Clin Endocrinol (Oxf) 86:761–771. https://doi.org/10.1111/cen.13315

    Article  PubMed  Google Scholar 

  7. Zelniker TA, Wiviott SD, Raz I et al (2019) SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 393:31–39. https://doi.org/10.1016/S0140-6736(18)32590-X

    Article  CAS  PubMed  Google Scholar 

  8. Refardt J, Winzeler B, Meienberg F et al (2017) Empagliflozin increases short-term urinary volume output in artificially induced syndrome of inappropriate antidiuresis. Int J Endocrinol 2017:7815690. https://doi.org/10.1155/2017/7815690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Refardt J, Imber C, Sailer CO et al (2020) A randomized trial of empagliflozin to increase plasma sodium levels in patients with the syndrome of inappropriate antidiuresis. J Am Soc Nephrol 31:615–624. https://doi.org/10.1681/ASN.2019090944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Refardt J, Imber C, Nobbenhuis R et al (2022) Treatment effect of the SGLT2 inhibitor empagliflozin on chronic syndrome of inappropriate antidiuresis: results of a randomized, double-blind, placebo-controlled, crossover trial. J Am Soc Nephrol. https://doi.org/10.1681/ASN.2022050623

    Article  PubMed  Google Scholar 

  11. Sarafidis P, Loutradis C, Ferro CJ, Ortiz A (2020) SGLT-2 inhibitors to treat hyponatremia associated with SIADH: a novel indication? Am J Nephrol 51:553–555

    Article  CAS  PubMed  Google Scholar 

  12. Nobbenhuis R, Refardt J, Vogt D et al (2021) Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers? Biomarkers 26:647–655. https://doi.org/10.1080/1354750X.2021.1970808

    Article  CAS  PubMed  Google Scholar 

  13. Potasso L, Refardt J, Meier C, Christ-Crain M (2021) Effect of hyponatremia normalization on osteoblast function in patients with SIAD. Eur J Endocrinol 186:1–8. https://doi.org/10.1530/EJE-21-0604

    Article  PubMed  Google Scholar 

  14. Gelbenegger G, Buchtele N, Schoergenhofer C et al (2017) Severe hypernatraemic dehydration and unconsciousness in a care-dependent inpatient treated with empagliflozin. Drug Saf - Case Rep 4:17. https://doi.org/10.1007/S40800-017-0058-8

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lee IH, Ahn DJ (2020) Dapagliflozin-associated euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus: a case report. Medicine (Baltimore) 99:e20228. https://doi.org/10.1097/MD.0000000000020228

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank their patient for giving consent for the publication of his medical history. The authors would also like to thank Prof. Ezio Ghigo and Prof. Silvia Grottoli for their support in this work.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti, 14, 10126, Turin, Italy

    Fabio Bioletto, Emanuele Varaldo, Nunzia Prencipe, Andrea Benso & Alessandro Maria Berton

Authors
  1. Fabio Bioletto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emanuele Varaldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nunzia Prencipe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea Benso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alessandro Maria Berton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessandro Maria Berton.

Ethics declarations

Competing interests

A.M.B. received fees from Thermo Fisher Diagnostics for previous editorial collaborations and oral presentations. The remaining authors report no conflicts of interest in this work.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bioletto, F., Varaldo, E., Prencipe, N. et al. Long-term efficacy of empagliflozin as an add-on treatment for chronic SIAD: a case report and literature review. Hormones 22, 343–347 (2023). https://doi.org/10.1007/s42000-023-00430-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42000-023-00430-0

Keywords

Search

Navigation