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REVIEW

Empagliflozin in Adults with Chronic Kidney Disease (CKD): Current Evidence and Place in Therapy

ORCID Icon, , , ORCID Icon &
Pages 133-142 | Received 19 Nov 2022, Accepted 25 Jan 2023, Published online: 02 Feb 2023

References

  • Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–2306. doi:10.1056/NEJMoa1811744
  • Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–1446. doi:10.1056/NEJMoa2024816
  • Wright EM. SGLT2 inhibitors: physiology and pharmacology. Kidney. 2021;2(12):2027–2037. doi:10.34067/KID.0002772021
  • Vrhovac I, Balen Eror D, Klessen D, et al. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Arch. 2015;467(9):1881–1898. doi:10.1007/s00424-014-1619-7
  • Garcia-Ropero A, Badimon JJ, Santos-Gallego CG. The pharmacokinetics and pharmacodynamics of SGLT2 inhibitors for type 2 diabetes mellitus: the latest developments. Expert Opin Drug Metab Toxicol. 2018;14(12):1287–1302. doi:10.1080/17425255.2018.1551877
  • van Bommel EJM, Muskiet MHA, van Baar MJB, et al. The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. Kidney Int. 2020;97(1):202–212. Erratum in: Kidney Int. 2020 May;97(5):1061. doi:10.1016/j.kint.2019.09.013
  • Scheen AJ. Pharmacokinetic/pharmacodynamic properties and clinical use of SGLT2 inhibitors in non-Asian and Asian patients with type 2 diabetes and chronic kidney disease. Clin Pharmacokinet. 2020;59(8):981–994. doi:10.1007/s40262-020-00885-z
  • Sarashina A, Koiwai K, Seman LJ, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects. Drug Metab Pharmacokinet. 2013;28(3):213–219. doi:10.2133/dmpk.dmpk-12-rg-082
  • Federal register. Available from: https://www.fda.gov/media/71287/download. Accessed August 24, 2022.
  • Ayoub BM, Mowaka S, Elzanfaly ES, Ashoush N, Elmazar MM, Mousa SA. Pharmacokinetic evaluation of empagliflozin in healthy Egyptian volunteers using LC-MS/MS and comparison with other Ethnic populations. Sci Rep. 2017;7(1):2583. doi:10.1038/s41598-017-02895-7
  • Heise T, Seewaldt-Becker E, Macha S, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab. 2013;15(7):613–621.
  • Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013;1(3):208–219. doi:10.1016/S2213-8587(13)70084-6
  • Häring H-U, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014;37(6):1650–1659. doi:10.2337/dc13-2105
  • Häring H-U, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013;36(11):3396–3404. doi:10.2337/dc12-2673
  • Kovacs CS, Seshiah V, Swallow R, et al. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2013;16:147–158. doi:10.1111/dom.12188
  • Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle H; EMPA-REG BASALTM trial investigators. Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2015;17(10):936–948. doi:10.1111/dom.12503
  • Schmidt DW, Argyropoulos C, Singh N. Are the protective effects of SGLT2 inhibitors a “class-effect” or are there differences between agents? Kidney. 2021;2(5):881–885. doi:10.34067/KID.0000622021)
  • Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–657. doi:10.1056/NEJMoa1611925
  • Heerspink HJL, Karasik A, Thuresson M, et al. Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study. Lancet Diabetes Endocrinol. 2020;8(1):27–35. doi:10.1016/S2213-8587(19)30384-5
  • Herrington WG, Staplin N, Wanner C, et al; EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2022;388(2):117–127. doi:10.1056/NEJMoa2204233
  • Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–2128. doi:10.1056/NEJMoa1504720
  • Zelniker TA, Wiviott SD, Raz I, 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(10166):31–39. Erratum in: Lancet. 2019 Jan 5;393(10166):30. doi:10.1016/S0140-6736(18)32590-X
  • Anker SD, Butler J, Filippatos G, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status: results from the EMPEROR-reduced trial. Circulation. 2021;143(4):337–349. doi:10.1161/CIRCULATIONAHA.120.051824
  • McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. doi:10.1056/NEJMoa1911303
  • Anker SD, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–1461. doi:10.1056/NEJMoa2107038
  • Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568–574. doi:10.1038/s41591-021-01659-1
  • Abraham WT, Lindenfeld J, Ponikowski P, et al. Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes. Eur Heart J. 2021;42(6):700–710. doi:10.1093/eurheartj/ehaa943
  • Kluger AY, Tecson KM, Lee AY, et al. Class effects of SGLT2 inhibitors on cardiorenal outcomes. Cardiovasc Diabetol. 2019;18(1):99. doi:10.1186/s12933-019-0903-4
  • Harrington J, Udell JA, Jones WS, et al. Empagliflozin in patients post myocardial infarction rationale and design of the EMPACT-MI trial. Am Heart J. 2022;253:S0002-8703(22)00095–3. doi:10.1016/j.ahj.2022.05.010
  • Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–1424. doi:10.1056/NEJMoa2022190
  • Kuchay MS, Krishan S, Mishra SK, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT trial). Diabetes Care. 2018;41(8):1801–1808. doi:10.2337/dc18-0165
  • Irace C, Casciaro F, Scavelli FB, et al. Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy. Cardiovasc Diabetol. 2018;17:1–9. doi:10.1186/s12933-018-0695-y
  • Dearborn JL, Qiao Y, Suri MFK, et al. Intracranial atherosclerosis and dementia the Atherosclerosis Risk in Communities (ARIC) study. Am Acad Neurol. 2017;88:1556–1563.
  • Pawlos A, Broncel M, Woźniak E, Gorzelak-Pabiś P. Neuroprotective effect of SGLT2 inhibitors. Molecules. 2021;26(23):7213. doi:10.3390/molecules26237213