Evidence-based Colombian consensus and expert opinion regarding the use of sodium-glucose cotransporter type 2 (iSGLT-2) inhibitors in the cardiorenal continuum in patients with chronic kidney disease
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Keywords

chronic kidney disease
type 2 diabetes mellitus
sodium-glucose cotransporter 2 inhibitors
cardiorenal syndrome
consensus
Delphi technique

How to Cite

1.
Montejo Hernández JD, Lopera JM, Rosselli C, Ronderos I, Daza R, Yama-Mosquera E, Flechas López JA, Jacome Guerrero RL, Contreras Villamizar KM, Machacón Miranda E, Henao Velásquez CM, Romero Jaller KC, Figueroa C, Mejía García CH, Hernández Sierra A, González Sánchez DA, de la Espriella V, Dávila M Ángel, Parra P, Guevara García JG, Uribe Betancur JM, Cárdenas-Garzón K, Zuluaga Peña JR, Zuluaga-Peña JP, Rico Fontalvo J. Evidence-based Colombian consensus and expert opinion regarding the use of sodium-glucose cotransporter type 2 (iSGLT-2) inhibitors in the cardiorenal continuum in patients with chronic kidney disease. Rev. Colomb. Nefrol. [Internet]. 2025 May 27 [cited 2025 Jun. 20];12(2). Available from: https://revistanefrologia.org/index.php/rcn/article/view/938

Abstract

Background: The treatment of chronic kidney disease (CKD) aims to decrease the risk of disease progression, emergence of complications, and risk of death, especially considering the cardiorenal continuum. Different clinical trials conducted with diabetic and non-diabetic individuals, as well as other risk groups such as heart failure and CKD, and antidiabetic drugs known as sodium-glucose cotransporter type 2 (iSGLT-2) inhibitors have shown beneficial effects on renal and cardiovascular outcomes.

Purpose: The objective of this consensus was to establish recommendations for management with iSGLT-2 by patients with CKD.

Methodology: The consensus was developed in the following stages: formation of the development group; definition of the research questions; search, screening, evaluation, and selection of evidence; synthesis and evaluation of the evidence; discussion in formal panels; generation of recommendations and expert judgment; and drafting, elaboration, and revision of the consensus document.

Results: The 22 clinical experts formulated 15 recommendations for the 12 research questions. The certainty of the evidence ranged from moderate to high based primarily on clinical practice guidelines, systematic literature reviews, clinical trials, and expert consensus. Most of the recommendations were weak.

Conclusion: The recommendations formulated serve as guidelines for implementing iSGLT-2 treatment in Colombian patients with CKD and some of its complications and/or comorbidities. As new scientific evidence emerges, these recommendations should be cautiously reconsidered and revised.

https://doi.org/10.22265/acnef.12.2.938
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References

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-314. https://doi.org/10.1016/j.kint.2023.10.018

Indolfi C, Barilla F, Basile C, Basso C, Cantaluppi V, Capasso G, et al. Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part II: From preventive strategies to treatment of patients with cardio-renal damage. G Ital Cardiol. 2022;23(10):793-812. http://dx.doi.org/10.1714/3881.38645

Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018;392(10159):2052-90. https://doi.org/10.1016/s0140-6736(18)31694-5

Cuenta de Alto Costo. Situación de la enfermedad renal crónica, la hipertensión arterial y la diabetes mellitus en Colombia 2023. Bogotá D. C.: CAC; 2024.

Go AS, Chertow GM, Fan D, Mcculloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296-305. https://doi.org/10.1056/nejmoa041031

Legrand K, Speyer E, Stengel B, Frimat L, Ngueyon Sime W, Massy ZA, et al. Perceived health and quality of life in patients with CKD, including those with kidney failure: findings from national surveys in France. Am J Kidney Dis. 2020;75(6):868-78. https://doi.org/10.1053/j.ajkd.2019.08.026

Yeung E, Bello AK, Levin A, Lunney M, Osman MA, Ye F, et al. Current status of health systems financing and oversight for end-stage kidney disease care: a cross-sectional global survey. BMJ Open. 2021;11(7):e047245. https://doi.org/10.1136/bmjopen-2020-047245

Borg R, Carlson N, Søndergaard J, Persson F. The growing challenge of chronic kidney disease: an overview of current knowledge. Int J Nephrol. 2023;2023:9609266. https://doi.org/10.1155/2023/9609266

Del Vecchio L, Beretta A, Jovane C, Peiti S, Genovesi S. A role for SGLT-2 inhibitors in treating non-diabetic chronic kidney disease. Drugs. 2021;81(13):1491-511. https://doi.org/10.1007/s40265-021-01573-3

Andrianesis V, Glykofridi S, Doupis J. The renal effects of SGLT2 inhibitors and a mini-review of the literature. Ther Adv Endocrinol Metab. 2016;7(5-6):212-28. https://doi.org/10.1177/2042018816676239

Brown E, Wilding JPH, Alam U, Barber TM, Karalliedde J, Cuthbertson DJ. The expanding role of SGLT2 inhibitors beyond glucose-lowering to cardiorenal protection. Ann Med. 2021;53(1):2072-89. https://doi.org/10.1080/07853890.2020.1841281

Podestà MA, Sabiu G, Galassi A, Ciceri P, Cozzolino M. SGLT2 inhibitors in diabetic and non-diabetic chronic kidney disease. Biomedicines. 2023;11(2):279. https://doi.org/10.3390/biomedicines11020279

Aristizábal-Colorado D, Ocampo-Posada M, Rivera-Martínez WA, Corredor-Rengifo D, Rico-Fontalvo J, Gómez-Mesa JE, et al. SGLT2 inhibitors and how they work beyond the glucosuric effect. State of the art. Am J Cardiovasc Drugs. 2024;24(6):707-18. https://doi.org/10.1007/s40256-024-00673-1

Di Costanzo A, Esposito G, Indolfi C, Spaccarotella CAM. SGLT2 inhibitors: a new therapeutical strategy to improve clinical outcomes in patients with chronic kidney diseases. Int J Mol Sci. 2023;24(10):8732. https://doi.org/10.3390/ijms24108732

Bailey CJ, Day C, Bellary S. Renal protection with SGLT2 inhibitors: effects in acute and chronic kidney disease. Curr Diab Rep. 2022;22(1):39-52. https://doi.org/10.1007/s11892-021-01442-z

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323-34. https://doi.org/10.1056/nejmoa1515920

Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Ways K, et al. Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care. 2015;38(3):403-11. https://doi.org/10.2337/dc14-1237

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(4):347-57. https://doi.org/10.1056/nejmoa1812389

McMurray JJV, DeMets DL, Inzucchi SE, Køber L, Kosiborod MN, Langkilde AM, et al. The dapagliflozin and prevention of adverse-outcomes in heart failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019;21(11):1402-11. https://doi.org/10.1002/ejhf.1548

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(15):1413-24. https://doi.org/10.1056/nejmoa2022190

Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-61. https://doi.org/10.1056/nejmoa2107038

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-98. https://doi.org/10.1056/nejmoa2206286

Cannon CP, Perkovic V, Agarwal R, Baldassarre J, Bakris G, Charytan DM, et al. Evaluating the effects of canagliflozin on cardiovascular and renal events in patients with type 2 diabetes mellitus and chronic kidney disease according to baseline HbA1c, including those with HbA1c <7%: results from the CREDENCE trial. Circulation. 2020;141(5):407-10. https://doi.org/10.1161/circulationaha.119.044359

Heerspink HJL, Stefánsson 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(15):1436-46. https://doi.org/10.1056/nejmoa2024816

Herrington W, Staplin N, Wanner C, Green J, Hauske S, Emberson J, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2022;388(2):117-27. https://doi.org/10.1056/nejmoa2204233

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(7):1463-76. https://doi.org/10.1016/j.ekir.2022.04.094

Lv J, Guo L, Wang R, Chen J. Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in nondiabetic patients with chronic kidney disease: a review of recent evidence. Kidney Dis. 2023;9(5):326-41. https://doi.org/10.1159/000530395

Dzau V, Braunwald E. Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J. 1991;121(4 pt. 1):1244-63. https://doi.org/10.1016/0002-8703(91)90694-d

Fontes-Carvalho R, Santos-Ferreira D, Raz I, Marx N, Ruschitzka F, Cosentino F. Protective effects of SGLT-2 inhibitors across the cardiorenal continuum: two faces of the same coin. Eur J Prev Cardiol. 2022;29(9):1352-60. https://doi.org/10.1093/eurjpc/zwab034

Escalada J. SGLT2 inhibitors and the cardiorenal continuum: a paradigm shift in the treatment of patients with T2D. Diabetes Ther. 2022;13(supl. 1):1-3. https://doi.org/10.1007/s13300-022-01281-5

McGill JB, Subramanian S. Safety of sodium-glucose co-transporter 2 inhibitors. Am J Cardiol. 2019;124(supl. 1):S45-52. https://doi.org/10.1016/j.amjcard.2019.10.029

Mascolo A, Di Napoli R, Balzano N, Cappetta D, Urbanek K, De Angelis A, Scisciola L, Di Meo I, Sullo MG, Rafaniello C, Sportiello L. Safety profile of sodium glucose co-transporter 2 (SGLT2) inhibitors: A brief summary. Front Cardiovasc Med. 2022 Sep 21;9:1010693. https://doi.org/10.3389/fcvm.2022.1010693

de Val ÍI, Mercado Castillo H, Díaz Melé MC. Euglycemic diabetic ketoacidosis associated with sodium-glucose cotransporter type 2 inhibitors. Med Clin. 2024;163(2):101-2. https://doi.org/10.1016/j.medcli.2024.01.025

Ministerio de Salud y Protección Social. Guía metodológica para la elaboración de guías de práctica clínica con evaluación económica en el sistema general de seguridad social en salud colombiano. Bogotá, Colombia: Ministerio de Salud y Protección Social; 2014.

Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010;182(18):E839-42. https://doi.org/10.1503/cmaj.090449

Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. https://doi.org/10.1186/s13643-016-0384-4

Whiting P, Savovi? J, Higgins JPT, Caldwell DM, Reeves BC, Shea B, et al. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol. 2016;69:225-34. https://doi.org/10.1016/j.jclinepi.2015.06.005

Higgins J, Green S, editores. Cochrane handbook for systematic reviews of interventions. Versión 5.1.0 [internet]. The Cochrane Collaboration; 2011 [citado 2024 Jun 10]. https://training.cochrane.org/handbook

García Valdés M, Suárez Marín M. El método Delphi para la consulta a expertos en la investigación científica. Rev Cub Salud Pública. 2013;39(2):253-67.

Manterola C, Asenjo-Lobos C, Otzen T. Jerarquización de la evidencia. Niveles de evidencia y grados de recomendación de uso actual. Rev Chil Infectol. 2014;31(6). http://dx.doi.org/10.4067/S0716-10182014000600011

Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, et al. GRADE evidence to decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016;353:i2016. https://doi.org/10.1136/bmj.i2016

Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. https://doi.org/10.1136/bmj.n160

Roddick AJ, Wonnacott A, Webb D, Watt A, Watson MA, Staplin N, et al. UK Kidney Association Clinical Practice Guideline: sodium-glucose co-transporter-2 (SGLT-2) inhibition in adults with kidney disease 2023 update. BMC Nephrol. 2023;24(1):310. https://doi.org/10.1186/s12882-023-03339-3

Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. 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):1788-801. https://doi.org/10.1016/s0140-6736(22)02074-8

Levin A, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684-701. https://doi.org/10.1016/j.kint.2023.10.016

Liew A, Lydia A, Matawaran BJ, Susantitaphong P, Tran HTB, Lim LL. Practical considerations for the use of SGLT-2 inhibitors in the Asia-Pacific countries-an expert consensus statement. Nephrology. 2023;28(8):415-24. https://doi.org/10.1111/nep.14167

Correa-Rotter R, Rosas-Guzmán J, Méndez-Durán A, Sebastián-Díaz MA, Díaz-Avendaño OC, Mehta-Pravin R, et al. Documento de consenso sobre el uso de iSGLT2 en pacientes con enfermedad renal crónica y diabetes. Gac Med Mex. 2022;158(M2):M1-12. https://doi.org/10.24875/GMM.M21000595

Li N, Lv D, Zhu X, Wei P, Gui Y, Liu S, et al. Effects of SGLT2 inhibitors on renal outcomes in patients with chronic kidney disease: a meta-analysis. Front Med. 2021;8:728089. https://doi.org/10.3389/fmed.2021.728089

Reyes-Farias CI, Reategui-Diaz M, Romani-Romani F, Prokop L. The effect of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes mellitus on cardiovascular and renal outcomes: a systematic review and meta-analysis. PLoS One. 2023;18(11):e0295059. https://doi.org/10.1371/journal.pone.0295059

Chen X, Wang J, Lin Y, Yao K, Xie Y, Zhou T. Cardiovascular outcomes and safety of SGLT2 inhibitors in chronic kidney disease patients. Front Endocrinol. 2023;14:1236404. https://doi.org/10.3389/fendo.2023.1236404

Chen HB, Yang YL, Yu TH, Li YH. SGLT2 inhibitors for the composite of cardiorenal outcome in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Eur J Pharmacol. 2022;936:175354. https://doi.org/10.1016/j.ejphar.2022.175354

Ali MU, Mancini GBJ, Fitzpatrick-Lewis D, Lewis R, Jovkovic M, Zieroth S, et al. The effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal outcomes: systematic review and meta-analysis. Can J Cardiol. 2022;38(8):1201-10. https://doi.org/10.1016/j.cjca.2022.05.011

Cao H, Rao X, Jia J, Yan T, Li D. Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2023;60(3):325-35. https://doi.org/10.1007/s00592-022-01989-7

Shiau CH, Tsau LY, Kao CC, Peng YC, Bai CH, Wu JC, et al. Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis. Int Urol Nephrol. 2024;56(4):1359-81. https://doi.org/10.1007/s11255-023-03789-6

Li LF, Ding LL, Zhan ZL, Qiu M. Meta-analysis on the safety and cardiorenal efficacy of SGLT2 inhibitors in patients without T2DM. Front Cardiovasc Med. 2021;8:690529. https://doi.org/10.3389/fcvm.2021.690529

Lin DSH, Yu AL, Lo HY, Lien CW, Lee JK, Chiang FT, et al. Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals. Eur J Endocrinol. 2023;189(1):S17-25. https://doi.org/10.1093/ejendo/lvad078

Obrador GT, Álvarez-Estévez G, Bellorín E, Bonnano-Hidalgo C, Clavero R, Correa-Rotter R, et al. Documento de consenso sobre nuevas terapias para retrasar la progresión de la enfermedad renal crónica con énfasis en los iSGLT-2: implicaciones para Latinoamérica. Nefro Latinoam. 2024;21:1-19. https://bonga.unisimon.edu.co/10.24875/NEFRO.M24000037

Krishnan A, Shankar M, Lerma EV, Wiegley N, GlomCon Editorial Team. Sodium glucose cotransporter 2 (SGLT2) inhibitors and CKD: are you a #flozinator? Kidney Med. 2023;5(4):100608. https://doi.org/10.1016/j.xkme.2023.100608

Tornero Molina F, Portilla Franco ME, Tornero Romero FJ, Herrero Calvo JA. Fragilidad y sarcopenia en la enfermedad renal crónica. Nefrología al Día. 2023:567.

Lee PC, Ganguly S, Goh SY. Weight loss associated with sodium-glucose cotransporter-2 inhibition: a review of evidence and underlying mechanisms. Obes Rev. 2018;19(12):1630-41. https://doi.org/10.1111/obr.12755

Abdul Wahab R, Cohen RV, le Roux CW. Recent advances in the treatment of patients with obesity and chronic kidney disease. Ann Med. 2023;55(1):2203517. https://doi.org/10.1080/07853890.2023.2203517

Yen FS, Wang SI, Hsu CC, Hwu CM, Wei JCC. Sodium-glucose cotransporter-2 inhibitors and nephritis among patients with systemic lupus erythematosus. JAMA Netw Open. 2024;7(6):e2416578. https://doi.org/10.1001/jamanetworkopen.2024.16578

Neuen BL, Heerspink HJL, Vart P, Claggett BL, Fletcher RA, Arnott C, et al. Estimated lifetime cardiovascular, kidney, and mortality benefits of combination treatment with SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal MRA compared with conventional care in patients with type 2 diabetes and albuminuria. Circulation. 2024;149(6):450-62. https://doi.org/10.1161/circulationaha.123.067584

de Boer IH, Khunti K, Sadusky T, Tuttle KR, Neumiller JJ, Rhee CM, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022;45(12):3075-90. https://doi.org/10.2337/dci22-0027

Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-63. https://doi.org/10.1056/nejmoa2110956

Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219-29. https://doi.org/10.1056/nejmoa2025845

Neuen BL, Jardine MJ. SGLT2 inhibitors and finerenone: one or the other or both? Nephrol Dial Transplant. 2022;37(7):1209-11. https://doi.org/10.1093/ndt/gfac046

Rossing P, Filippatos G, Agarwal R, Anker SD, Pitt B, Ruilope LM, et al. Finerenone in predominantly advanced CKD and type 2 diabetes with or without sodium-glucose cotransporter-2 inhibitor therapy. Kidney Int Rep. 2022;7(1):36-45. https://doi.org/10.1016/j.ekir.2021.10.008

Tsukamoto S, Morita R, Yamada T, Urate S, Azushima K, Uneda K, et al. Cardiovascular and kidney outcomes of combination therapy with sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists in patients with type 2 diabetes and chronic kidney disease: a systematic review and network meta-analysis. Diabetes Res Clin Pract. 2022;194:110161. https://doi.org/10.1016/j.diabres.2022.110161

Heerspink HJL, Vart P, Jongs N, Neuen BL, Bakris G, Claggett B, et al. Estimated lifetime benefit of novel pharmacological therapies in patients with type 2 diabetes and chronic kidney disease: a joint analysis of randomized controlled clinical trials. Diabetes Obes Metab. 2023;25(11):3327-36. https://doi.org/10.1111/dom.15232

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