The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Sodium-Glucose Cotransporter 2 Inhibitors for Chronic Kidney Disease: A Comprehensive Review

SGLT2 억제제와 만성 콩팥병

  • Su Hyun Song (Division of Nephrology, Department of Internal Medicine, Chonnam National University Medical School) ;
  • Eun Hui Bae (Division of Nephrology, Department of Internal Medicine, Chonnam National University Medical School)
  • 송수현 (전남대학교 의과대학 신장내과학교실) ;
  • 배은희 (전남대학교 의과대학 신장내과학교실)
  • Received : 2024.02.06
  • Accepted : 2024.03.14
  • Published : 2024.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

Chronic Kidney Disease (CKD) is a major global health burden. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated potential in slowing CKD progression. We evaluated the expanding role of SGLT2 inhibitors, emphasizing their renoprotective benefits in diabetic and non-diabetic CKD patients. We also investigated the underlying mechanisms, including the reduction of glomerular hypertension via modulation of tubuloglomerular feedback. Our study critically analyzed current indications for SGLT2 inhibitor therapy based on recent clinical trial data. To optimize patient outcomes, we present a comprehensive analysis of practical considerations for the prescription of SGLT2 inhibitors, including the potential initial decline in the estimated glomerular filtration rate and a review of adverse events.

Keywords

Acknowledgement

This research was supported by a grant (BCRI24032) of Chonnam National University Hospital Biomedical Research Institute.

References

  1. Mather A, Pollock C. Glucose handling by the kidney. Kidney Int Suppl 2011;120:S1-S6.
  2. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011;91:733-794.
  3. Zehra T, Cupples WA, Braam B. Tubuloglomerular feedback synchronization in nephrovascular networks. J Am Soc Nephrol 2021;32:1293-1304.
  4. Tonneijck L, Muskiet MH, Smits MM, et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol 2017;28:1023-1039.
  5. Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 2017;60:215-225.
  6. Cherney DZI, Cooper ME, Tikkanen I, et al. Pooled analysis of phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int 2018;93:231-244.
  7. Heerspink HJL, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab 2013;15:853-862.
  8. Cherney DZ, Perkins BA, Soleymanlou N, et al. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol 2014;13:28.
  9. Mihai S, Codrici E, Popescu ID, et al. Inflammation-related mechanisms in chronic kidney disease prediction, progression, and outcome. J Immunol Res 2018;2018:2180373.
  10. Dekkers CCJ, Petrykiv S, Laverman GD, Cherney DZ, Gansevoort RT, Heerspink HJL. Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers. Diabetes Obes Metab 2018;20:1988-1993.
  11. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-2128.
  12. Cherney DZI, Zinman B, Inzucchi SE, et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2017;5:610-621.
  13. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644-657.
  14. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347-357.
  15. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-2306.
  16. Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436-1446.
  17. Wheeler DC, Stefansson BV, Jongs N, et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol 2021;9:22-31.
  18. The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023;388:117-127.
  19. Chertow GM, Vart P, Jongs N, et al. Effects of dapagliflozin in stage 4 chronic kidney disease. J Am Soc Nephrol 2021;32:2352-2361.
  20. Cherney DZI, Dekkers CCJ, Barbour SJ, et al. Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial. Lancet Diabetes Endocrinol 2020;8:582-593.
  21. Wheeler DC, Toto RD, Stefansson BV, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int 2021;100:215-224.
  22. EMPA-KIDNEY Collaborative Group. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol 2024;12:51-60.
  23. Koshino A, Neuen BL, Jongs N, et al. Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial. Cardiovasc Diabetol 2023;22:330.
  24. Ishikawa N, Oguri T, Isobe T, Fujitaka K, Kohno N. SGLT gene expression in primary lung cancers and their metastatic lesions. Jpn J Cancer Res 2001;92:874-879.
  25. Zhou J, Zhu J, Yu SJ, et al. Sodium-glucose co-transporter-2 (SGLT-2) inhibition reduces glucose uptake to induce breast cancer cell growth arrest through AMPK/mTOR pathway. Biomed Pharmacother 2020;132:110821.
  26. Yamamoto L, Yamashita S, Nomiyama T, et al. Sodium-glucose cotransporter 2 inhibitor canagliflozin attenuates lung cancer cell proliferation in vitro. Diabetol Int 2021;12:389-398.
  27. Kaji K, Nishimura N, Seki K, et al. Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake. Int J Cancer 2018;142:1712-1722.
  28. Lega IC, Bronskill SE, Campitelli MA, et al. Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: a population-based study of older women and men with diabetes. Diabetes Obes Metab 2019;21:2394-2404.
  29. Uitrakul S, Aksonnam K, Srivichai P, Wicheannarat S, Incomenoy S. The incidence and risk factors of urinary tract infection in patients with type 2 diabetes mellitus using SGLT2 inhibitors: a real-world observational study. Medicines (Basel) 2022;9:59.
  30. Thong KY, Yadagiri M, Barnes DJ, et al. Clinical risk factors predicting genital fungal infections with sodium-glucose cotransporter 2 inhibitor treatment: the ABCD nationwide dapagliflozin audit. Prim Care Diabetes 2018;12:45-50.
  31. Blau JE, Tella SH, Taylor SI, Rother KI. Ketoacidosis associated with SGLT2 inhibitor treatment: analysis of FAERS data. Diabetes Metab Res Rev 2017;33:e2924.
  32. Palmer BF, Clegg DJ. Euglycemic ketoacidosis as a complication of SGLT2 inhibitor therapy. Clin J Am Soc Nephrol 2021;16:1284-1291.
  33. Daniele G, Xiong J, Solis-Herrera C, et al. Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes. Diabetes Care 2016;39:2036-2041.
  34. Ryan PB, Buse JB, Schuemie MJ, et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: a real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes Metab 2018;20:2585-2597.
  35. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2019;7:845-854.
  36. Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations. Kidney Int Rep 2022;7:1463-1476.