Cardiovasc Prev Pharmacother.  2025 Apr;7(2):44-49. 10.36011/cpp.2025.7.e4.

Clinical impact and practical use of sodium-glucose cotransporter 2 inhibitors for patients with chronic kidney disease

Affiliations
  • 1Cardiovascular Division, Department of Internal Medicine, Good Samsun Hospital, Busan, Korea

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have transformed the treatment of both cardiovascular and renal diseases. Although originally developed for glycemic control in type 2 diabetes mellitus, these agents have demonstrated significant benefits by reducing cardiovascular events and slowing the progression of kidney disease, even in patients without diabetes. Landmark trials, including EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58, and DAPA-HF, consistently demonstrated reductions in heart failure hospitalizations and renal deterioration among patients at high cardiovascular risk. However, many of these studies excluded patients with advanced chronic kidney disease (CKD), limiting the generalizability of their findings for this population. More recent investigations, such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY, have focused on patients with CKD and confirmed that SGLT2 inhibitors offer significant renal and cardiovascular protection regardless of diabetic status. This review summarizes key clinical trials, outlining their design and outcomes with a particular emphasis on inclusion and exclusion criteria and the implications for CKD populations. Further, it discusses the practical application and safety considerations of SGLT2 inhibitors in nephrology, underscoring their emerging role as a fundamental therapeutic strategy in CKD management.

Keyword

Sodium-glucose transporter 2 inhibitors; Chronic kidney disease; Cardiovascular diseases; Chronic renal insufficiency; Randomized controlled trials

Reference

1. 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; 373:2117–28. DOI: 10.1056/nejmoa1504720. PMID: 26378978.
Article
2. Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377:2099. DOI: 10.1056/nejmoa1611925. PMID: 28605608.
Article
3. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380:347–57. DOI: 10.1056/nejmoa1812389. PMID: 30415602.
Article
4. McMurray JJ, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381:1995–2008. DOI: 10.1056/nejmoa1911303. PMID: 31535829.
5. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019; 380:2295–306. DOI: 10.1056/nejmoa1811744. PMID: 30990260.
Article
6. Heerspink HJ, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020; 383:1436–46. DOI: 10.1056/nejmoa2024816. PMID: 32970396.
Article
7. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023; 388:117–27. DOI: 10.1056/nejmoa2204233. PMID: 36331190.
Article
8. Neuen BL, Young T, Heerspink HJ, Neal B, Perkovic V, Billot L, 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; 7:845–54. DOI: 10.1016/s2213-8587(19)30256-6. PMID: 31495651.
Article
9. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019; 393:31–9. DOI: 10.1016/s0140-6736(18)32590-x. PMID: 30424892.
Article
10. Kosiborod M, Cavender MA, Fu AZ, Wilding JP, Khunti K, Holl RW, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation. 2017; 136:249–59. DOI: 10.1161/circulationaha.117.029190. PMID: 28522450.
Article
11. Patorno E, Pawar A, Franklin JM, Najafzadeh M, Deruaz-Luyet A, Brodovicz KG, et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the EMPRISE study. Circulation. 2019; 139:2822–30. DOI: 10.1161/circulationaha.118.039177. PMID: 30955357.
Article
12. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383:1413–24. DOI: 10.1056/nejmoa2022190. PMID: 32865377.
13. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020; 98:S1–115. DOI: 10.1016/j.kint.2020.06.019. PMID: 32998798.
14. Tuttle KR, Brosius FC, Cavender MA, Fioretto P, Fowler KJ, Heerspink HJ, et al. SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation. Diabetes. 2021; 70:1–16. DOI: 10.2337/dbi20-0040. PMID: 33106255.
Article
15. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42:3599–726. DOI: 10.1093/eurheartj/ehab368. PMID: 34447992.
Article
16. Mavrakanas TA, Tsoukas MA, Brophy JM, Sharma A, Gariani K. SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis. Sci Rep. 2023; 13:15922. DOI: 10.1038/s41598-023-42989-z. PMID: 37741858.
Article
17. Theodorakopoulou MP, Alexandrou ME, Tsitouridis A, Kamperidis V, Pella E, Xanthopoulos A, et al. Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2024; 10:329–41. DOI: 10.1093/ehjcvp/pvae003. PMID: 38218589.
Article
18. Siddiqui R, Obi Y, Dossabhoy NR, Shafi T. Is there a role for SGLT2 inhibitors in patients with end-stage kidney disease? Curr Hypertens Rep. 2024; 26:463–74. DOI: 10.1007/s11906-024-01314-3. PMID: 38913113.
Article
19. Stepanova N. SGLT2 inhibitors in peritoneal dialysis: a promising frontier toward improved patient outcomes. Ren Replace Ther. 2024; 10:5. DOI: 10.1186/s41100-024-00523-5.
Article
20. Spasovski G, Rroji M, Hristov G, Bushljetikj O, Spahia N, Rambabova Bushletikj I. A new hope on the horizon for kidney and cardiovascular protection with SGLT2 inhibitors, GLP-1 receptor agonists, and mineralocorticoid receptor antagonists in type 2 diabetic and chronic kidney disease patients. Metab Syndr Relat Disord. 2024; 22:170–8. DOI: 10.1089/met.2023.0227. PMID: 38386800.
Article
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