How Low Can You Go? Safety and Efficacy of Sodium-Glucose Cotransporter Inhibitors in Decreased Renal Function

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications primarily used as either monotherapy or add-on therapy in those with type 2 diabetes. Given the mechanism of SGLT2 inhibitors, a renal dose adjustment or glomerular filtration rate cutoff in which it should be avoided due to decreased efficacy is recommended. However, studies have shown that these agents may possess renal benefits through decreasing serum glucose levels as well as decreasing intraglomerular pressure and albuminuria. The safety and benefits of SGLT2 inhibitors in patients with decreased renal function is an area of uncertainty.

Keywords

sodium-glucose cotransporter 2 inhibitors SGLT2 inhibitors renal function

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References

Kalra

. Sodium glucose co-transporter-2 (SGLT2) inhibitors: a review of their basic and clinical pharmacology. Diabetes Ther. 2014;5(2):355-366.

Cowart

Stachura

. Glucosuria. In: Walker

, Hall

, Hurst

, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. Boston, MA: Butterworth; 1990:653-657.

Invokana [Package Insert]. Titusville, NJ: Janssen Ortho LLC.; 2013.

Jardiance [Package Insert]. Ridgefield, CT: Boehringer Pharmaceuticals, Inc.; 2016.

Farxiga [Package Insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2014.

Heerspink

HJL

Stafánsson

Correa-Rotter

, et al. Dapagliflozin in patients with chronic kidney disease. Engl J Med. 2020;383:1436-1446.

Fioretto

Zambon

Rossato

, et al. SGLT2 inhibitors and the diabetic kidney. Diabetes Care. 2016;39(2):165-171.

American Diabetes Association . Microvascular complications and foot care: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021; 44(suppl 1):S151-S167.

Zinman

Wanner

Lachin

, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. Engl J Med. 2015;373(22):2117-2128.

10.

Neal

Perkovic

Mahaffey

, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. Engl J Med. 2017;377(7):644-657.

11.

Perkovic

Jardine

Neal

, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. Engl J Med. 2019;380(24):2295-2306.

12.

Cannon

Pratley

Dagogo-Jack

, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. Engl J Med. 2020;383:1425-1435.

13.

Rabizadeh

Nakhjavani

Esteghamati

. Cardiovascular and renal benefits of SGLT2 inhibitors: a narrative review. Int J Endocrinol Metab. 2019;17(2):e84353.

14.

American Diabetes Association . Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2021. Diabetes Care 2021;44(suppl 1):S111-S124.

15.

Wiviott

Raz

Bonaca

, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. Engl J Med. 2019;380(4):347-357.

16.

McMurray

JJV

Solomon

Inzucchi

, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. Engl J Med. 2019;381(21):1995-2008.

17.

Packer

Anker

Butler

, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. Engl J Med. 2020;383:1413-1424.

18.

Steglatro [Package Insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2017.

19.

Food and Drug Administration . FDA Removed Boxed Warning about Risk of Leg and Foot Amputations for the Diabetes Medicine Canagliflozin (Invokana, Invokamet, Invokamet XR). [revised 2020 Sep 9; cited 2021 Apr 3]. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin.

20.

Erythropoulou-Kaltsidou

Polychronopoulos

Tziomalos

. Sodium-glucose co-transporter 2 inhibitors and fracture risk. Diabetes Ther. 2020;11(1):7-14.

21.

ClinicalTrials.gov . Bethesda, MD: National Library of Medicine (US). 2000. Identifier NCT03057951, Empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction (EMPEROR-Preserved); 2021 Mar 24 [cited 2021 Apr 5]; [about 2 screens]. Available from: https://clinicaltrials.gov/ct2/show/NCT03057951

22.

ClinicalTrials.gov . Bethesda, MD: National Library of Medicine (US). 2000. Identifier NCT03619213, Dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure (DELIVER); 2021 Mar 9 [cited 2021 Apr 5]; [about 2 screens]. Available from: https://clinicaltrials.gov/ct2/show/NCT03619213

23.

ClinicalTrials.gov . Bethesda, MD: National Library of Medicine (US). 2000. Identifier NCT03717194, Effect of ertugliflozin on cardiac function in diabetes (ERTU-GLS); 2021 Mar 30 [cited 2021 Apr 5]; [about 2 screens]. Available from: https://clinicaltrials.gov/ct2/show/NCT03717194

24.

ClinicalTrials.gov . Bethesda, MD: National Library of Medicine (US). 2000. Identifier NCT03982381, SGLT2 inhibitor or metformin as standard treatment of early stage type 2 diabetes (SMARTEST); 2021 Mar 24 [cited 2021 Apr 5]; [about 2 screens]. Available from: https://clinicaltrials.gov/ct2/show/NCT03982381

25.

KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S8.

26.

Düsing

. Mega clinical trials which have shaped the RAS intervention clinical practice. Ther Adv Cardiovasc Dis. 2016;10(3):133–150.