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Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes—cardiovascular and renal benefits in patients with chronic kidney disease

  • Tamara Y. Milder
  • Sophie L. Stocker
  • Dorit Samocha-Bonet
  • Richard O. Day
  • Jerry R. GreenfieldEmail author
Review

Abstract

Purpose

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have important cardiovascular and renal benefits in adults with type 2 diabetes who have or are at high risk of cardiovascular and renal disease. These benefits are seen in patients with impaired renal function where the glucose-lowering effects are not observed. Here, we review the pharmacokinetics and pharmacology of SGLT2 inhibitors in relation to cardiovascular and renal outcomes in patients with chronic kidney disease (CKD).

Methods

We searched PubMed and EMBASE for original research, meta-analyses and review articles relevant to the pharmacokinetics, and cardiac and renal outcomes of SGLT2 inhibitors published up until June 2019. Specialist society guidelines and publications were also consulted.

Results

Renal impairment is currently a contraindication to SGLT2 inhibitor use largely due to limited anti-hyperglycaemic efficacy. However, in cardiovascular outcome trials, and a dedicated renal outcome trial, cardiovascular and renal benefits were seen in participants with CKD suggesting that mechanisms underlying the cardiovascular and renal benefits of SGLT2 inhibitors are likely largely independent of the glucose-lowering action of these agents.

Conclusions

Despite minimal glycaemic benefits in patients with type 2 diabetes and stage 3 CKD, the cardiovascular and renal benefits of these agents are preserved in this group of patients. Whether these agents have cardiovascular and renal benefits in patients with stage 4 CKD and patients with non-diabetic CKD needs further research.

Keywords

SGLT2 inhibitor Pharmacokinetics Cardiovascular outcomes Efficacy Safety Chronic kidney disease 

Notes

Authors’ contribution

TYM drafted the manuscript. SLS, DSB, ROD and JRG revised the manuscript critically for important intellectual content. All authors approved the final draft.

Funding information

There was no funding support for this research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

228_2019_2732_MOESM1_ESM.docx (16 kb)
Supplementary Table 1 (DOCX 15 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Diabetes and EndocrinologySt. Vincent’s HospitalSydneyAustralia
  2. 2.Department of Clinical Pharmacology and ToxicologySt. Vincent’s HospitalSydneyAustralia
  3. 3.St. Vincent’s Clinical SchoolUniversity of NSWSydneyAustralia
  4. 4.Diabetes and MetabolismGarvan Institute of Medical ResearchSydneyAustralia

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