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

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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.

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Authors and Affiliations

  1. Department of Diabetes and Endocrinology, St. Vincent’s Hospital, Sydney, NSW, Australia

    Tamara Y. Milder & Jerry R. Greenfield

  2. Department of Clinical Pharmacology and Toxicology, St. Vincent’s Hospital, Sydney, NSW, Australia

    Tamara Y. Milder, Sophie L. Stocker & Richard O. Day

  3. St. Vincent’s Clinical School, University of NSW, Sydney, NSW, Australia

    Tamara Y. Milder, Sophie L. Stocker, Dorit Samocha-Bonet, Richard O. Day & Jerry R. Greenfield

  4. Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia

    Tamara Y. Milder, Dorit Samocha-Bonet & Jerry R. Greenfield

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  1. Tamara Y. Milder
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  2. Sophie L. Stocker
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TYM drafted the manuscript. SLS, DSB, ROD and JRG revised the manuscript critically for important intellectual content. All authors approved the final draft.

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Correspondence to Jerry R. Greenfield.

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Milder, T.Y., Stocker, S.L., Samocha-Bonet, D. et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes—cardiovascular and renal benefits in patients with chronic kidney disease. Eur J Clin Pharmacol 75, 1481–1490 (2019). https://doi.org/10.1007/s00228-019-02732-y

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