Chapter 6: SGLT-2 cotransport inhibitors
DOI:
https://doi.org/10.47196/diab.v58i2Sup.789Keywords:
SGLT-2 inhibitors, diabetic kidney disease, diabetes mellitusAbstract
SGLT-2 inhibitors have changed the horizon of treatment for patients with DM2 and also for those without DM who suffer from kidney disease and/or CVD. We will review the current evidence for these drugs called gliflozins.
During studies conducted to primarily evaluate CV safety in T2DM populations, microvascular complications, such as diabetic kidney disease (DKD), were evaluated as prespecified secondary objectives.
In the EMPA-REG OUTCOME study, focused on patients with T2DM with established CVD, the relative risk (RR) was reduced by 39% in the prespecified endpoint of incident nephropathy or worsening of nephropathy, with similar results with both doses of empagliflozin, 10 mg and 25 mg2. A post hoc analysis of said study in patients without CKD at the start of treatment, eGFR ≥60 ml/min/1.73 m2 or ACR ≤30 mg/g), 47% showed an RR for incidence of CKD of 0.67 ( 0.47-0.94) and the renal composite (doubling of baseline creatinine, start of dialysis or transplant or kidney death) of 0.31 (0.16-0.63).
References
I. Inserra F, Lavenia G, Taylor MF, Castellaro C. Protección cardiovascular, renal y cerebral de los iSGLT2. Mecanismos hemodinámicos, tisulares y celulares implicados. Rev Nefrol Dial Traspl 2023;43:184-196.
II. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375:323-334.
III. Levin A, Perkovic V, Wheeler DC, et al. Empagliflozin and cardiovascular and kidney outcomes across KDIGO risk categories: post hoc analysis of a randomized, double blind, placebo-controlled, multinational trial. Clin J Am Soc Nephrol 2020;15:1433-44.
IV. 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.
V. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347-35.
VI. Mosenzon O, Raz I, Wiviott SDet al. Dapagliflozin and prevention of kidney disease among patients with type 2 diabetes: post hoc analyses from the DECLARE-TIMI 58 trial. Diabetes Care 2022;45:2350-9.
VII. 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.
VIII. Cohen CM, Schechter M, Rozenberg A, et al. Long-term, real-world kidney outcomes with SGLT2i versus DPP4i in type 2 diabetes without cardiovascular or kidney disease. CJASN 2023;18:1153-1162.
IX. Jongs N, Greene T, Chertow GM, et al; DAPA-CKD Trial Committees and Investigators. Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol 2021;9:755-766.
X. Herrington WG, Staplin N, Wanner C, Green JB, et al.; The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023; 12;388:117-127.
XI. 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.
XII. Sarraju A, Li J, Cannon CP, et al. Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure. Results from the CREDENCE trial. Am Heart J 2021; 233:141-148.
XIII. Neuen BL, Young T, Heerspink HJL, et al. SGLT-2 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.
XIV. 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.
XV. 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. Lancet Diabetes Endocrinol 2021;9:22-31.
XVI. Nuffield Department of Population Health Renal Studies Group, & SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (2022). Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 2022;400(10365):1788-1801.
XVII. Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001;134:629-36.
XVIII. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436-1446.
XIX. Rahman H, Khan SU, Lone AN, et al. Sodium-glucose cotransporter-2 inhibitors and primary prevention of atherosclerotic cardiovascular disease. A meta-Analysis of randomized trials and systematic review. J Am Heart Assoc 2023;12(16):e030578.
XX. McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martínez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019;381:1995-2008.
XXI. Mc Causland FR, Claggett BL, Vaduganathan M, et al. Dapagliflozin and kidney outcomes in patients with heart failure with mildly reduced or preserved ejection fraction. A prespecified analysis of the DELIVER. Randomized clinical trial. JAMA Cardiol 2023; 8:56-65.
XXII. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020;383:1413-24.
XXIII. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejction fraction. N Engl J Med 2021;385:1451-1461.
XXIV. Wheeler DC, Toto RD, Stefánsson BV, et al. DAPA-CKD Trial Committees and Investigators. 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.
XXV. 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. Nephrol Dial Transplant 2022;37:1609-1615.
XXVI. Mosenzon O, Wiviott SD, Heerspink HJL, et al. The effect of dapagliflozin on albuminuria in DECLARE-TIMI 58. Diabetes Care 2021;44:1805-1815.
XXVII. Zinman B, et al. Empagliflozin, cardiovascular outcomes and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-2128.
XXVIII. Solomon S, McMurray JV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2022;387:1089-1098.
XXIX. Fernández-Fernández B, Sarafidis P, Soler MJ, Ortiz A. EMPA-KIDNEY: expanding the range of kidney protection by SGLT2 inhibitors. Clin Kidney J 2023 Jun 16;16(8):1187-1198.
XXX. Mascolo A, Di Napoli R, Balzano N, et al. Safety profile of SLGT2 inhibitors. A brief summary. Front Cardiovasc Med 2022;9:1010693.
XXXI. Inserra F, Castellaro C, Elbert A, Forte E, Waisman G, et al. Toma de posición. Efecto de los iSGLT2 sobre la presión arterial, el daño vascular, la enfermedad renal y el riesgo cardiovascular asociado. Rev Argent Cardiol 2023;91(Sup 6):1-18.
XXXII. Packer M. Critical reanalysis of the mechanisms underlying the cardiorenal benefits of SGLT-2 inhibitors and reaffirmation of the nutrient deprivation signaling/autophagy hypothesis. Circulation 2022;146:1383-1405.
XXXIII. Sanz RL, Inserra F, García-Menéndez S, et al. Metabolic syndrome and cardiac remodeling due to mitochondrial oxidative stress involving gliflozins and sirtuins. Curr Hypertens Rep 2023;25:91-106.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 on behalf of the authors. Reproduction rights: Argentine Society of Diabetes
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Dirección Nacional de Derecho de Autor, Exp. N° 5.333.129. Instituto Nacional de la Propiedad Industrial, Marca «Revista de la Sociedad Argentina de Diabetes - Asociación Civil» N° de concesión 2.605.405 y N° de disposición 1.404/13.
La Revista de la SAD está licenciada bajo Licencia Creative Commons Atribución – No Comercial – Sin Obra Derivada 4.0 Internacional.
Por otra parte, la Revista SAD permite que los autores mantengan los derechos de autor sin restricciones.
