Unveiling renoprotection: A comprehensive review of SGLT2 inhibitors, with emphasis on empagliflozin in the treatment of chronic kidney disease
Vol 5, Issue 1, 2024
VIEWS - 90 (Abstract)
Abstract
Chronic kidney disease (CKD) affects 10%–13% of the global population, necessitating innovative treatments. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, shows promise by reducing glycated hemoglobin and benefiting kidney and cardiovascular health. By spotlighting renoprotective mechanisms like glucose control and anti-inflammatory effects, insights from trials such as EMPA-REG OUTCOME unveil decreased kidney disease progression, improved eGFR, and reduced albuminuria with empagliflozin. Safety profiles and comparisons: Evaluating safety profiles, potential adverse events, and comparisons with other SGLT2 inhibitors provides a nuanced perspective on the therapeutic potential of empagliflozin. The review emphasizes the importance of diverse CKD population studies, continuous safety monitoring, and exploring SGLT2 inhibitors in specific demographics. In summary, empagliflozin emerges as a versatile therapeutic option in the SGLT2 inhibitor class for CKD, reshaping disease management. Final thoughts: Ongoing research and vigilant monitoring are crucial for maximizing the potential of SGLT2 inhibitors, especially empagliflozin, to enhance patient well-being in CKD.
Keywords
Full Text:
PDFReferences
1. Eckardt KU, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: From subspecialty to global health burden. The Lancet. 2013, 382(9887): 158-169. doi: 10.1016/s0140-6736(13)60439-0
2. Levey AS, Coresh J, Bolton K, et al. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American Journal of Kidney Diseases. 2002, 39(2 Suppl 1): S1-S266.
3. Notice. Kidney International Supplements. 2013, 3(1): 1. doi: 10.1038/kisup.2012.73
4. Ammirati AL. Chronic Kidney Disease. Revista da Associação Médica Brasileira. 2020, 66(suppl 1): S3-S9. doi: 10.1590/1806-9282.66.s1.3
5. Levin A. The clinical epidemiology of cardiovascular diseases in chronic kidney disease: Clinical Epidemiology of Cardiovascular Disease in Chronic Kidney Disease Prior to Dialysis. Seminars in Dialysis. 2003, 16(2): 101-105. doi: 10.1046/j.1525-139x.2003.16025.x
6. Webster AC, Nagler EV, Morton RL, et al. Chronic Kidney Disease. The Lancet. 2017, 389(10075): 1238-1252. doi: 10.1016/s0140-6736(16)32064-5
7. Drawz P, Rahman M. Chronic Kidney Disease. Annals of Internal Medicine. 2015, 162(11): ITC1-ITC16. doi: 10.7326/aitc201506020
8. Mende CW. Chronic Kidney Disease and SGLT2 Inhibitors: A Review of the Evolving Treatment Landscape. Advances in Therapy. 2021, 39(1): 148-164. doi: 10.1007/s12325-021-01994-2
9. Cheung AK, Chang TI, Cushman WC, et al. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney International. 2021, 99(3): S1-S87. doi: 10.1016/j.kint.2020.11.003
10. Fried LF, Emanuele N, Zhang JH, et al. Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. New England Journal of Medicine. 2013, 369(20): 1892-1903. doi: 10.1056/nejmoa1303154
11. Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events. New England Journal of Medicine. 2008, 358(15): 1547-1559. doi: 10.1056/nejmoa0801317
12. Parving HH, Brenner BM, McMurray JJV, et al. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes. New England Journal of Medicine. 2012, 367(23): 2204-2213. doi: 10.1056/nejmoa1208799
13. Locatelli F. How long can dialysis be postponed by low protein diet and ACE inhibitors? Nephrology Dialysis Transplantation. 1999, 14(6): 1360-1364. doi: 10.1093/ndt/14.6.1360
14. Block G, Hulbert-Shearon T, Levin N, et al. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study. American Journal of Kidney Diseases. 1998, 31(4): 607-617. doi: 10.1053/ajkd.1998.v31.pm9531176
15. Levin NW, Hulbert-Shearon TE, Strawderman RL. Which causes of death are related to hyperphosphataemia in hemodialysis (HD) patients? Journal of the American Society of Nephrology. 1998, 9: 217A.
16. Portolés J, Torralbo A, Martin P, et al. Cardiovascular effects of recombinant human erythropoietin in predialysis patients. American Journal of Kidney Diseases. 1997, 29(4): 541-548. doi: 10.1016/s0272-6386(97)90335-8
17. Hayashi T, Suzuki A, Shoji T, et al. Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. American Journal of Kidney Diseases. 2000, 35(2): 250-256. doi: 10.1016/s0272-6386(00)70334-9
18. Locatelli F, Del Vecchio L, D’Amico M, et al. Is It the Agent or the Blood Pressure Level that Matters for Renal Protection in Chronic Nephropathies? Journal of the American Society of Nephrology. 2002, 13(suppl_3): S196-S201. doi: 10.1097/01.asn.0000032521.12410.29
19. Biesenbach G, Janko O, Zazgornik J. Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus. Nephrology Dialysis Transplantation. 1994, 9(8): 1097-1102. doi: 10.1093/ndt/9.8.1097
20. Locatelli F, Marcelli D, Conte F, et al. Patient selection affects end-stage renal disease outcome comparisons. Kidney International. 2000, 57: S94-S99. doi: 10.1046/j.1523-1755.2000.07416.x
21. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2001, 345(12): 861-869. doi: 10.1056/nejmoa011161
22. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes. New England Journal of Medicine. 2001, 345(12): 851-860. doi: 10.1056/nejmoa011303
23. Lewis EJ, Hunsicker LG, Bain RP, et al. The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy. New England Journal of Medicine. 1993, 329(20): 1456-1462. doi: 10.1056/nejm199311113292004
24. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019, 380(24): 2295-2306. doi: 10.1056/nejmoa1811744
25. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. New England Journal of Medicine. 2020, 383(15): 1436-1446. doi: 10.1056/nejmoa2024816
26. Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. New England Journal of Medicine. 2020, 383(23): 2219-2229. doi: 10.1056/nejmoa2025845
27. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. New England Journal of Medicine. 2021, 385(24): 2252-2263. doi: 10.1056/nejmoa2110956
28. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. New England Journal of Medicine. 2016, 375(4): 323-334. doi: 10.1056/nejmoa1515920
29. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. New England Journal of Medicine. 2017, 377(7): 644-657. doi: 10.1056/nejmoa1611925
30. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of Medicine. 2019, 380(4): 347-357. doi: 10.1056/nejmoa1812389
31. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine. 2016, 374(11): 1092-1094. doi: 10.1056/nejmc1600827
32. Wheeler DC, Stefánsson 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. The Lancet Diabetes & Endocrinology. 2021, 9(1): 22-31. doi: 10.1016/s2213-8587(20)30369-7
33. Staplin N, Roddick AJ, Emberson J, et al. Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials. eClinicalMedicine. 2021, 41: 101163. doi: 10.1016/j.eclinm.2021.101163
34. Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. The Lancet Diabetes & Endocrinology. 2018, 6(9): 691-704. doi: 10.1016/s2213-8587(18)30141-4
35. The EMPA-Kidney Collaborative Group. Empagliflozin in Patients with Chronic Kidney Disease. New England Journal of Medicine. 2023, 388: 117-127. doi: 10.1056/nejmoa2204233
36. Busko M. Europe approves empagliflozin for chronic kidney disease. Available online: https://www.medscape.com/viewarticle/994859?form=fpf (accessed on 31 January 2024).
37. Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2016, 60(2): 215-225. doi: 10.1007/s00125-016-4157-3
38. Skrabic R, Kumric M, Vrdoljak J, et al. SGLT2 Inhibitors in Chronic Kidney Disease: From Mechanisms to Clinical Practice. Biomedicines. 2022, 10(10): 2458. doi: 10.3390/biomedicines10102458
39. Bailey CJ, Day C, Bellary S. Renal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease. Current Diabetes Reports. 2022, 22(1): 39-52. doi: 10.1007/s11892-021-01442-z
40. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes. Annals of Internal Medicine. 2013, 159(4): 262. doi: 10.7326/0003-4819-159-4-201308200-00007
41. Devineni D, Curtin CR, Polidori D, et al. Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Sodium Glucose Co‐Transporter 2 Inhibitor, in Subjects with Type 2 Diabetes Mellitus. The Journal of Clinical Pharmacology. 2013, 53(6): 601-610. doi: 10.1002/jcph.88
42. Gao YM, Feng ST, Wen Y, et al. Cardiorenal protection of SGLT2 inhibitors—Perspectives from metabolic reprogramming. eBioMedicine. 2022, 83: 104215. doi: 10.1016/j.ebiom.2022.104215
43. Delanaye P, Jager KJ, Bökenkamp A, et al. CKD: A Call for an Age-Adapted Definition. Journal of the American Society of Nephrology. 2019, 30(10): 1785-1805. doi: 10.1681/asn.2019030238
44. Anders HJ, Peired AJ, Romagnani P. SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, ‘diabetic nephropathy’, IgA nephropathy and podocytopathies with FSGS lesions. Nephrology Dialysis Transplantation. 2020, 37(9): 1609-1615. doi: 10.1093/ndt/gfaa329
45. Ishibashi Y, Matsui T, Yamagishi S. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation. Hormone and Metabolic Research. 2015, 48(3): 191-195. doi: 10.1055/s-0035-1555791
46. Ojima A, Matsui T, Nishino Y, et al. Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis. Hormone and Metabolic Research. 2015, 47(9): 686-692. doi: 10.1055/s-0034-1395609
47. Garofalo C, Borrelli S, Liberti M, et al. SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects. Medicina. 2019, 55(6): 268. doi: 10.3390/medicina55060268
48. Levey AS, Gansevoort RT, Coresh J, et al. Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in collaboration with the US Food and Drug Administration and European Medicines Agency. American Journal of Kidney Diseases. 2020, 75: 84-104.
49. Boehringer Ingelheim. BI 10773 (Empagliflozin) cardiovascular outcome event trial in Type 2 Diabetes mellitus patients (EMPA-REG OUTCOME). Available online: https://clinicaltrials.gov/study/NCT01131676 (accessed on 25 November 2023).
50. Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. The Lancet Diabetes & Endocrinology. 2014, 2(5): 369-384. doi: 10.1016/s2213-8587(13)70208-0
51. EMPA-Kidney Collaborative Group. Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. Nephrology Dialysis Transplantation. 2022, 37(7): 1317-1329. doi: 10.1093/ndt/gfac040
52. Mosley JF, Smith L, Everton E, et al. Sodium-glucose linked transporter 2 (SGLT2) inhibitors in the management of type-2 diabetes: a drug class overview. Pharmacology & Therapeutics. 2015, 40(7): 451-462.
53. Toyama T, Neuen BL, Jun M, et al. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta‐analysis. Diabetes, Obesity and Metabolism. 2019, 21(5): 1237-1250. doi: 10.1111/dom.13648
54. Nelinson DS, Sosa JM, Chilton RJ. SGLT2 inhibitors: a narrative review of efficacy and safety. Journal of Osteopathic Medicine. 2021, 121(2): 229-239. doi: 10.1515/jom-2020-0153
55. Nakamura A, Miyoshi H, Kameda H, et al. Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria. Diabetology & Metabolic Syndrome. 2020, 12(1). doi: 10.1186/s13098-020-0516-9
56. Sorensen MD, Krieger JN. Fournier’s Gangrene: Epidemiology and Outcomes in the General US Population. Urologia Internationalis. 2016, 97(3): 249-259. doi: 10.1159/000445695
57. Bersoff-Matcha SJ, Chamberlain C, Cao C, et al. Fournier Gangrene Associated with Sodium–Glucose Cotransporter-2 Inhibitors. Annals of Internal Medicine. 2019, 170(11): 764. doi: 10.7326/m19-0085
58. Phillip M, Mathieu C, Lind M, et al. Long‐term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: pooled 52‐week outcomes from the DEPICT‐1 and ‐2 studies. Diabetes, Obesity and Metabolism. 2020, 23(2): 549-560. doi: 10.1111/dom.14248
59. Dandona P, Mathieu C, Phillip M, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes: The DEPICT-1 52-Week Study. Diabetes Care. 2018, 41(12): 2552-2559. doi: 10.2337/dc18-1087
60. Mathieu C, Dandona P, Gillard P, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care. 2018, 41(9): 1938-1946. doi: 10.2337/dc18-0623
61. Mascolo A, Scavone C, Scisciola L, et al. SGLT-2 inhibitors reduce the risk of cerebrovascular/cardiovascular outcomes and mortality: A systematic review and meta-analysis of retrospective cohort studies. Pharmacological Research. 2021, 172: 105836. doi: 10.1016/j.phrs.2021.105836
62. 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, Obesity and Metabolism. 2018, 20(11): 2585-2597. doi: 10.1111/dom.13424
63. Brailovski E, Kim RB, Juurlink D. Rosuvastatin Myotoxicity After Starting Canagliflozin Treatment: A Case Report. Annals of Internal Medicine. 2020, 173(7): 585-587. doi: 10.7326/l20-0549
64. Cai X, Gao X, Yang W, et al. No disparity of the efficacy and all‐cause mortality between Asian and non‐Asian type 2 diabetes patients with sodium–glucose cotransporter 2 inhibitors treatment: A meta‐analysis. Journal of Diabetes Investigation. 2017, 9(4): 850-861. doi: 10.1111/jdi.12760
65. Mukai J, Kanno S, Kubota R. A literature review and meta-analysis of safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus. Scientific Reports. 2021, 11(1). doi: 10.1038/s41598-021-92925-2
66. Jiang B, Cheng Z, Liu F, et al. Renoprotection with sodium‐glucose cotransporter‐2 inhibitors in children: Knowns and unknowns. Nephrology. 2021, 27(2): 126-132. doi: 10.1111/nep.13979
67. Shi Z, Gao F, Liu W, et al. Comparative Efficacy of Dapagliflozin and Empagliflozin of a Fixed Dose in Heart Failure: A Network Meta-Analysis. Frontiers in Cardiovascular Medicine. 2022, 9. doi: 10.3389/fcvm.2022.869272
68. Boehringer Ingelheim. EMPA-KIDNEY (The Study of Heart and Kidney Protection with Empagliflozin). Available online: https://classic.clinicaltrials.gov/ct2/show/NCT03594110 (accessed on 25 November 2023).
DOI: https://doi.org/10.54517/urr.v5i1.2402
(90 Abstract Views, 0 PDF Downloads)
Refbacks
- There are currently no refbacks.
eISSN
2811-0161
Publication Frequency
Semi-annual
Indexing & Archiving
