Review

. 2019 Nov;75(11):1481-1490.

doi: 10.1007/s00228-019-02732-y. Epub 2019 Aug 3.

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

Tamara Y Milder^{1

2

3

4}, Sophie L Stocker^{2

3}, Dorit Samocha-Bonet^{3

4}, Richard O Day^{2

3}, Jerry R Greenfield^{5

6

7}

Affiliations

¹ Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia.
² Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia.
³ St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia.
⁴ Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁵ Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia. j.greenfield@garvan.org.au.
⁶ St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia. j.greenfield@garvan.org.au.
⁷ Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia. j.greenfield@garvan.org.au.

PMID: 31377891
DOI: 10.1007/s00228-019-02732-y

Review

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

Tamara Y Milder et al. Eur J Clin Pharmacol. 2019 Nov.

. 2019 Nov;75(11):1481-1490.

doi: 10.1007/s00228-019-02732-y. Epub 2019 Aug 3.

Authors

Tamara Y Milder^{1

2

3

4}, Sophie L Stocker^{2

3}, Dorit Samocha-Bonet^{3

4}, Richard O Day^{2

3}, Jerry R Greenfield^{5

6

7}

Affiliations

¹ Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia.
² Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia.
³ St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia.
⁴ Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁵ Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia. j.greenfield@garvan.org.au.
⁶ St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia. j.greenfield@garvan.org.au.
⁷ Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia. j.greenfield@garvan.org.au.

PMID: 31377891
DOI: 10.1007/s00228-019-02732-y

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: Cardiovascular outcomes; Chronic kidney disease; Efficacy; Pharmacokinetics; SGLT2 inhibitor; Safety.

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Cited by

Sodium-glucose co-transporter 2 inhibitor therapy: use in chronic kidney disease and adjunctive sodium restriction.
Tiwary M, Milder TY, Stocker SL, Day RO, Greenfield JR. Tiwary M, et al. Intern Med J. 2022 Oct;52(10):1666-1676. doi: 10.1111/imj.15727. Epub 2022 May 27. Intern Med J. 2022. PMID: 35257458 Free PMC article. Review.
Potential Safety Issues with Use of Sodium-Glucose Cotransporter 2 Inhibitors, Particularly in People with Type 2 Diabetes and Chronic Kidney Disease.
Milder TY, Stocker SL, Day RO, Greenfield JR. Milder TY, et al. Drug Saf. 2020 Dec;43(12):1211-1221. doi: 10.1007/s40264-020-01010-6. Epub 2020 Oct 23. Drug Saf. 2020. PMID: 33095409 Free PMC article. Review.

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

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