SGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the art
Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms un...
- Autores:
-
Aristizábal‑Colorado, David
Ocampo‑Posada, Martín
Rivera‑Martínez, Wilfredo Antonio
Corredor‑Rengifo, David
Rico‑Fontalvo, Jorge
Gómez‑Mesa, Juan Esteban
Duque‑Ossman, John Jairo
Abreu‑Lomba, Alin
- Tipo de recurso:
- Fecha de publicación:
- 2024
- Institución:
- Universidad Simón Bolívar
- Repositorio:
- Repositorio Digital USB
- Idioma:
- eng
- OAI Identifier:
- oai:bonga.unisimon.edu.co:20.500.12442/15416
- Acceso en línea:
- https://hdl.handle.net/20.500.12442/15416
https://doi.org/10.1007/s40256-024-00673-1
https://link.springer.com/article/10.1007/s40256-024-00673-1
- Palabra clave:
- Rights
- closedAccess
- License
- Attribution-NonCommercial-NoDerivs 3.0 United States
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SGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the art |
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SGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the art |
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SGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the art |
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SGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the art |
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SGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the art |
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Aristizábal‑Colorado, David Ocampo‑Posada, Martín Rivera‑Martínez, Wilfredo Antonio Corredor‑Rengifo, David Rico‑Fontalvo, Jorge Gómez‑Mesa, Juan Esteban Duque‑Ossman, John Jairo Abreu‑Lomba, Alin |
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Aristizábal‑Colorado, David Ocampo‑Posada, Martín Rivera‑Martínez, Wilfredo Antonio Corredor‑Rengifo, David Rico‑Fontalvo, Jorge Gómez‑Mesa, Juan Esteban Duque‑Ossman, John Jairo Abreu‑Lomba, Alin |
| description |
Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group’s mechanism of action. |
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2024 |
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2024-08-26T22:11:31Z |
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2024 |
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Aristizábal-Colorado, D., Ocampo-Posada, M., Rivera-Martínez, W.A. et al. SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art. Am J Cardiovasc Drugs (2024). https://doi.org/10.1007/s40256-024-00673-1 |
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1179187X (En línea) 11753277 (Impreso) |
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https://hdl.handle.net/20.500.12442/15416 |
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https://doi.org/10.1007/s40256-024-00673-1 |
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https://link.springer.com/article/10.1007/s40256-024-00673-1 |
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Aristizábal-Colorado, D., Ocampo-Posada, M., Rivera-Martínez, W.A. et al. SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art. Am J Cardiovasc Drugs (2024). https://doi.org/10.1007/s40256-024-00673-1 1179187X (En línea) 11753277 (Impreso) |
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eng |
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eng |
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Aristizábal‑Colorado, David68d7494f-ac81-4146-b8df-d989a92ef8ee-1Ocampo‑Posada, Martín4544031f-1f13-4c14-8e55-9951c5a29f64-1Rivera‑Martínez, Wilfredo Antonioe58a20fe-9a93-42a9-91a4-23232b4061ad-1Corredor‑Rengifo, Davidfa08b81d-3aef-4fcb-b2ce-5c770aad6def-1Rico‑Fontalvo, Jorgea156782c-eb0d-4540-a7cb-92742ffaee75-1Gómez‑Mesa, Juan Estebanf3f086f6-6efe-481e-8ce1-a0456b014614-1Duque‑Ossman, John Jairo295ca250-a47d-4d47-ad40-a3e8ac7a1fe6-1Abreu‑Lomba, Alin5c64a8c6-95ae-4e0f-b8c2-cb6d95aa36f3-12024-08-26T22:11:31Z2024-08-26T22:11:31Z2024Aristizábal-Colorado, D., Ocampo-Posada, M., Rivera-Martínez, W.A. et al. SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art. Am J Cardiovasc Drugs (2024). https://doi.org/10.1007/s40256-024-00673-11179187X (En línea)11753277 (Impreso)https://hdl.handle.net/20.500.12442/15416https://doi.org/10.1007/s40256-024-00673-1https://link.springer.com/article/10.1007/s40256-024-00673-1Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group’s mechanism of action.pdfengSpringerAttribution-NonCommercial-NoDerivs 3.0 United Stateshttp://creativecommons.org/licenses/by-nc-nd/3.0/us/info:eu-repo/semantics/closedAccesshttp://purl.org/coar/access_right/c_14cbAmerican Journal of Cardiovascular DrugsAm J Cardiovasc DrugsSGLT2 Inhibitors and how they work beyond the glucosuric effect. State of the artinfo:eu-repo/semantics/articleArtículo científicohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1Liu L, Simon B, Shi J, Mallhi AK, Eisen HJ. Impact of diabetes mellitus on risk of cardiovascular disease and all-cause mortality: Evidence on health outcomes and antidiabetic treatment in United States adults. World J Diabetes. 2016;7:449–61. https://doi.org/10.4239/wjd.v7.i18.449.National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis Off J Natl Kidney Found. 2012;60:850–86. https://doi.org/10.1053/j.ajkd.2012.07.005.Wu B, Bell K, Stanford A, Kern DM, Tunceli O, Vupputuri S, et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns—NHANES 2007–2012. BMJ Open Diabetes Res Care. 2016;4: e000154. https://doi.org/10.1136/bmjdrc-2015-000154.Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22. https://doi.org/10.1056/NEJMoa1603827.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. https://doi.org/10.1056/NEJMoa1504720.Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295–306. https://doi.org/10.1056/NEJMoa1811744.Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, et al. ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). Eur Heart J. 2023. https://doi.org/10.1093/eurheartj/ehad192.McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599–726. https://doi.org/10.1093/eurheartj/ehab368.Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020;17:761–72. https://doi.org/10.1038/s41569-020-0406-8.Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:2099. https://doi.org/10.1056/NEJMc1712572.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. https://doi.org/10.1056/NEJMoa1812389.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. The Lancet. 2019;393:31–9. https://doi.org/10.1016/S0140-6736(18)32590-X.Wright EM, Loo DD, Panayotova-Heiermann M, Lostao MP, Hirayama BH, Mackenzie B, et al. “Active” sugar transport in eukaryotes. J Exp Biol. 1994;196:197–212. https://doi.org/10.1242/jeb.196.1.197.Biegus J, Fudim M, Salah HM, Heerspink HJL, Voors AA, Ponikowski P. Sodium–glucose cotransporter-2 inhibitors in heart failure: Potential decongestive mechanisms and current clinical studies. Eur J Heart Fail. https://doi.org/10.1002/ejhf.2967.Packer M. SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism. Nat Rev Cardiol. 2023;20:443–62. https://doi.org/10.1038/s41569-022-00824-4.Salvatore T, Galiero R, Caturano A, Rinaldi L, Di Martino A, Albanese G, et al. An overview of the cardiorenal protective mechanisms of SGLT2 inhibitors. Int J Mol Sci. 2022;23:3651. https://doi.org/10.3390/ijms23073651.Palmiero G, Cesaro A, Vetrano E, Pafundi PC, Galiero R, Caturano A, et al. Impact of SGLT2 inhibitors on heart failure: from pathophysiology to clinical effects. Int J Mol Sci. 2021;22:5863. https://doi.org/10.3390/ijms22115863.Pabel S, Hamdani N, Luedde M, Sossalla S. SGLT2 inhibitors and their mode of action in heart failure-has the mystery been unravelled? Curr Heart Fail Rep. 2021;18:315–28. https://doi.org/10.1007/s11897-021-00529-8.Tsai K-F, Chen Y-L, Chiou TT-Y, Chu T-H, Li L-C, Ng H-Y, et al. Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases. Antioxid Basel Switz. 2021;10:1166. https://doi.org/10.3390/antiox10081166.Storgaard H, Gluud LL, Bennett C, Grøndahl MF, Christensen MB, Knop FK, et al. Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS ONE. 2016;11: e0166125. https://doi.org/10.1371/journal.pone.0166125.Rajeev SP, Cuthbertson DJ, Wilding JPH. Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition. Diabetes Obes Metab. 2016;18:125–34. https://doi.org/10.1111/dom.12578.Cefalu WT, Leiter LA, Yoon K-H, Arias P, Niskanen L, Xie J, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet Lond Engl. 2013;382:941–50. https://doi.org/10.1016/S0140-6736(13)60683-2.Yagi S, Hirata Y, Ise T, Kusunose K, Yamada H, Fukuda D, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2017;9:78. https://doi.org/10.1186/s13098-017-0275-4.Xu L, Nagata N, Nagashimada M, Zhuge F, Ni Y, Chen G, et al. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing m2 macrophages in diet-induced obese mice. EBioMedicine. 2017;20:137–49. https://doi.org/10.1016/j.ebiom.2017.05.028.Youssef ME, Yahya G, Popoviciu MS, Cavalu S, Abd-Eldayem MA, Saber S. Unlocking the full potential of SGLT2 inhibitors: expanding applications beyond glycemic control. Int J Mol Sci. 2023;24:6039. https://doi.org/10.3390/ijms24076039.Jin Z, Yuan Y, Zheng C, Liu S, Weng H. Effects of sodium-glucose co-transporter 2 inhibitors on liver fibrosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: an updated meta-analysis of randomized controlled trials. J Diabetes Complications. 2023;37: 108558. https://doi.org/10.1016/j.jdiacomp.2023.108558.Szekeres Z, Sandor B, Bognar Z, Ramadan FHJ, Palfi A, Bodis B, et al. Clinical study of metabolic parameters, leptin and the SGLT2 inhibitor empagliflozin among patients with obesity and type 2 diabetes. Int J Mol Sci. 2023;24:4405. https://doi.org/10.3390/ijms24054405.Yaribeygi H, Maleki M, Butler AE, Jamialahmadi T, Sahebkar A. Sodium-glucose co-transporter-2 inhibitors and epicardial adiposity. 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Heart Fail Rev. 2017;22:889–902. https://doi.org/10.1007/s10741-017-9644-1.Sattar N, Fitchett D, Hantel S, George JT, Zinman B. Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial. Diabetologia. 2018;61:2155–63. https://doi.org/10.1007/s00125-018-4702-3.Scheen AJ. Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: a common comorbidity associated with severe complications. Diabetes Metab. 2019;45:213–23. https://doi.org/10.1016/j.diabet.2019.01.008.Bajaj HS, Brown RE, Bhullar L, Sohi N, Kalra S, Aronson R. SGLT2 inhibitors and incretin agents: associations with alanine aminotransferase activity in type 2 diabetes. Diabetes Metab. 2018;44:493–9. https://doi.org/10.1016/j.diabet.2018.08.001.Burns KD, Cherney D. Renal angiotensinogen and sodium-glucose cotransporter-2 inhibition: insights from experimental diabetic kidney disease. Am J Nephrol. 2019;49:328–30. https://doi.org/10.1159/000499598.Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: A systematic review and meta-analysis. J Am Soc Hypertens. 2014;8:262-275.e9. https://doi.org/10.1016/j.jash.2014.01.007.Teo YH, Teo YN, Syn NL, Kow CS, Yoong CSY, Tan BYQ, et al. Effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus: a systematic review and meta-analysis of randomized-controlled trials. J Am Heart Assoc. 2021;10: e019463. https://doi.org/10.1161/JAHA.120.019463.Fioretto P, Mansfield TA, Ptaszynska A, Yavin Y, Johnsson E, Parikh S. Long-term safety of dapagliflozin in older patients with type 2 diabetes mellitus: a pooled analysis of phase IIb/III studies. Drugs Aging. 2016;33:511–22. https://doi.org/10.1007/s40266-016-0382-1.Oshima N, Onimaru H, Yamashiro A, Goto H, Tanoue K, Fukunaga T, et al. SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats. Hypertens Res Off J Jpn Soc Hypertens. 2024;47:46–54. https://doi.org/10.1038/s41440-023-01417-5.Ahwin P, Martinez D. The relationship between SGLT2 and systemic blood pressure regulation. Hypertens Res. 2024;47:2094–103. https://doi.org/10.1038/s41440-024-01723-6.Barnett AH, Mithal A, Manassie J, Jones R, Rattunde H, Woerle HJ, 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. Lancet Diabetes Endocrinol. 2014;2:369–84. https://doi.org/10.1016/S2213-8587(13)70208-0.Joannidis M, Klein SJ, Ostermann M. 10 myths about frusemide. Intensive Care Med. 2019;45:545–8. https://doi.org/10.1007/s00134-018-5502-4.Scheen AJ. An update on the safety of SGLT2 inhibitors. Expert Opin Drug Saf. 2019;18:295–311. https://doi.org/10.1080/14740338.2019.1602116.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. https://doi.org/10.3389/fmed.2021.728089.Vallon V, Richter K, Blantz RC, Thomson S, Osswald H. Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol JASN. 1999;10:2569–76. https://doi.org/10.1681/ASN.V10122569.Alicic RZ, Johnson EJ, Tuttle KR. SGLT2 inhibition for the prevention and treatment of diabetic kidney disease: a review. Am J Kidney Dis Off J Natl Kidney Found. 2018;72:267–77. https://doi.org/10.1053/j.ajkd.2018.03.022.Cassis P, Locatelli M, Cerullo D, Corna D, Buelli S, Zanchi C, et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy. JCI Insight. 2018;3(e98720):98720. https://doi.org/10.1172/jci.insight.98720.Vallon V, Gerasimova M, Rose MA, Masuda T, Satriano J, Mayoux E, et al. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol. 2014;306:F194-204. https://doi.org/10.1152/ajprenal.00520.2013.Bae JH, Park E-G, Kim S, Kim SG, Hahn S, Kim NH. Effects of sodium-glucose cotransporter 2 inhibitors on renal outcomes in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Sci Rep. 2019;9:13009. https://doi.org/10.1038/s41598-019-49525-y.Tuttle KR. Digging deep into cells to find mechanisms of kidney protection by SGLT2 inhibitors. J Clin Invest. 2023. https://doi.org/10.1172/JCI167700.Rohm TV, Meier DT, Olefsky JM, Donath MY. 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