Nephroprotective Effect of SGLT2 Inhibitors in Chronic Kidney Disease Patients

Authors

  • Ueakan Pharadonpadjai Faculty of Pharmaceutical Sciences, Chulalongkorn University
  • Somratai Vadcharavivad Faculty of Pharmaceutical Sciences, Chulalongkorn University

Keywords:

canagliflozin, dapagliflozin, empagliflozin, SGLT2 inhibitors, chronic kidney disease

Abstract

SGLT2 inhibitors are blood glucose-lowering agents that inhibit sodium-glucose cotransporter type 2 in the renal proximal tubule. SGLT2 inhibitors increase glycosuria, and therefore blood glucose reduced. Randomized control trials in chronic kidney disease patients with proteinuria demonstrated the benefits of canagliflozin, dapagliflozin, and empagliflozin in approximately 30% reduction of the composite outcomes of end-stage kidney disease, a doubling of serum creatinine or a sustained decline in the estimated glomerular filtration rate, and death from renal or cardiovascular causes among chronic kidney disease patients with or without diabetes mellitus. Most of the study patients had moderate to severe proteinuria despite receiving maximum tolerated renin-angiotensin system inhibitor treatment. Genital fungal infection, volume depletion, and diabetic ketoacidosis are concerns that need to be appropriately monitored.

Author Biographies

Ueakan Pharadonpadjai, Faculty of Pharmaceutical Sciences, Chulalongkorn University

Pharm.D. (Pharm Care)

Somratai Vadcharavivad, Faculty of Pharmaceutical Sciences, Chulalongkorn University

Pharm.D., BCP.

References

Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev. 2005;21(1):31–8. doi: 10.1002/dmrr.532.

สมาคมโรคไตแห่งประเทศไทย. ข้อแนะนำเวชปฏิบัติการดูแลผู้ป่วยโรคไตเรื้อรัง ก่อนการบำบัดทดแทนไต พ.ศ. 2565 ฉบับปรับปรุงเพิ่มเติม. กรุงเทพฯ: ศรีเมืองการพิมพ์; 2565.

Rossing P, Caramori ML, Chan JC, Heerspink HJ, Hurst C, Khunti K, et al. Executive summary of the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease: an update based on rapidly emerging new evidence. Kidney Int. 2022;102(5):990-9. doi: 10.1016/j.kint.2022.06.013.

Elsayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. The American Diabetes Association (ADA) pharmacologic approaches to glycemic treatment: standards of care in diabetes-2023. Diabetes Care. 2023;46(Suppl1):S140-57. doi: 10.2337/dc23-S009.

Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(21):2099. doi: 10.1056/NEJMc1712572.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. doi: 10.1056/NEJMoa1504720.

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. doi: 10.1056/NEJMoa1911303.

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089–98. doi: 10.1056/NEJMoa2206286.

Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61. doi: 10.1056/NEJMoa2107038.

Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306. doi: 10.1056/NEJMoa1811744.

Heerspink HJL, Stefánsson B V., Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. doi: 10.1056/NEJMoa2024816.

Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-27. doi: 10.1056/NEJMoa2204233.

Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010;27(2):136–42. doi: 10.1111/j.1464-5491.2009.02894.x.

Zeng Q, Zhou Q, Liu W, Wang Y, Xu X, Xu D. Mechanisms and perspectives of sodium-glucose co-transporter 2 inhibitors in heart failure. Front Cardiovasc Med. 2021;8:636152. doi: 10.3389/fcvm.2021.636152.

Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015;75(1):33–59. doi: 10.1007/s40265-014-0337-y.

Tsai KF, Chen YL, Chiou TTY, Chu TH, Li LC, Ng HY, et al. Emergence of SGLT2 inhibitors as powerful antioxidants in human diseases. Antioxidants (Basel). 2021;10(8):1166. doi: 10.3390/antiox10081166.

Miyata KN, Zhang SL, Chan JSD. The rationale and evidence for SGLT2 inhibitors as a treatment for nondiabetic glomerular disease. Glomerular Dis. 2021;1(1):21-33. doi: 10.1159/000513659.

Lytvyn Y, Bjornstad P, Udell JA, Lovshin JA, Cherney DZI. Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation. 2017;136(17):1643–58. doi: 10.1161/CIRCULATIONAHA.117.030012.

Cherney DZI, Charbonnel B, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley R, et al. Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial. Diabetologia. 2021;64(6):1256–67. doi: 10.1007/s00125-021-05407-5.

McGill JB, Subramanian S. Safety of sodium-glucose co-transporter 2 inhibitors. Am J Cardiol. 2019;132(10 Suppl):S49-57. doi: 10.1016/j.amjmed.2019.08.006.

Inzucchi SE, Iliev H, Pfarr E, Zinman B. Empagliflozin and assessment of lower-limb amputations in the EMPA-REG OUTCOME trial. Diabetes Care. 2018;41(1):e4-5. doi: 10.2337/dc17-1551.

Downloads

Published

2023-08-28

How to Cite

1.
Pharadonpadjai U, Vadcharavivad S. Nephroprotective Effect of SGLT2 Inhibitors in Chronic Kidney Disease Patients. Thai J Hosp Pharm [internet]. 2023 Aug. 28 [cited 2026 Jan. 15];33(2):218-29. available from: https://he02.tci-thaijo.org/index.php/TJHP/article/view/261393

Issue

Section

Review Article