Fármacos antidiabéticos en cardioprotección: más allá del control de la glicemia
DOI:
https://doi.org/10.22370/syc.1.1.2025.5395.Palabras clave:
myocardial infarction, Sodium-Glucose Transporter 2 Inhibitors, SemaglutideResumen
Las cardiopatías isquémicas constituyen la principal causa de mortalidad cardiovascular, con proyecciones de hasta 20 millones de muertes anuales para 2050. Estas patologías se originan por la interrupción del flujo sanguíneo coronario (isquemia) seguida de su restablecimiento (reperfusión), fenómeno que genera daño miocárdico y disfunción ventricular izquierda. El daño por isquemia/reperfusión (I/R) involucra estrés oxidativo, alteraciones del calcio intracelular y lesión microvascular, lo que amplifica el tamaño del infarto y favorece el desarrollo de insuficiencia cardíaca.
A pesar del uso de terapias convencionales, persiste la necesidad de estrategias que reduzcan el daño miocárdico. Los inhibidores de SGLT2 y los agonistas del receptor GLP-1 (GLP-1RA) han mostrado efectos cardiovasculares beneficiosos independientes de su acción antidiabética. Por lo tanto, este artículo de revisión tiene objetivo discutir la clínica y preclínica asociada al uso de inhibidores de SGLT2 y agonistas GLP-1RA como agentes cardioprotectores, destacando sus potenciales beneficios terapéuticos e identificando aquellos aspectos que aún requieren ser dilucidados.
Los inhibidores del SGLT2, como la empagliflozina y la dapagliflozina, mejoran los resultados cardiovasculares en la insuficiencia cardíaca independientemente del control glicémico, aunque su impacto en el infarto de miocardio sigue siendo incierto. Por otra parte, fármacos como la semaglutida, ha demostrado reducir significativamente eventos cardiovasculares mayores en pacientes obesos sin diabetes, sugiriendo efectos cardioprotectores directos sobre el miocardio.
Estudios preclínicos evidencian que su acción podría involucrar tanto cardiomiocitos como células endoteliales, contribuyendo a la preservación de la función cardíaca. En conjunto, los SGLT2i y GLP-1RA surgen como alternativas prometedoras para la cardioprotección, aunque se requieren estudios clínicos adicionales para dilucidar sus mecanismos y optimizar su eficacia traslacional.
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World Heart Federation. World Heart Report 2023: Confronting the World’s Number One Killer. Ginebra, Suiza: World Heart Federation; 2023.
Chong B, Jayabaskaran J, Jauhari SM, Chan SP, Goh R, Kueh MTW, Li H, Chin YH, Kong G, Anand VV, Wang JW, Muthiah M, Jain V, Mehta A, Lim SL, Foo R, Figtree GA, Nicholls SJ, Mamas MA, Januzzi JL, Chew NWS, Richards AM, Chan MY. Global burden of cardiovascular diseases: projections from 2025 to 2050. Eur J Prev Cardiol. 2025;32(11):1001-1015.
Del Buono MG, Moroni F, Montone RA, Azzalini L, Sanna T, Abbate A. Ischemic Cardiomyopathy and Heart Failure After Acute Myocardial Infarction. Curr Cardiol Rep. 2022;24(10):1505-1515.
Sharif D, Matanis W, Sharif-Rasslan A, Rosenschein U. Doppler echocardiographic myocardial stunning index predicts recovery of left ventricular systolic function after primary percutaneous coronary intervention. Echocardiography. 2016;33(10):1465-1471.
Zhao BH, Ruze A, Zhao L, Li QL, Tang J, Xiefukaiti N, Gai MT, Deng AX, Shan XF, Gao XM. The role and mechanisms of microvascular damage in the ischemic myocardium. Cell Mol Life Sci. 2023;80(11):341.
Niccoli G, Montone RA, Ibanez B, Thiele H, Crea F, Heusch G, Bulluck H, Hausenloy DJ, Berry C, Stiermaier T, Camici PG, Eitel I. Optimized Treatment of ST-Elevation Myocardial Infarction. Circ Res. 2019;125(2):245-258.
Galli M, Niccoli G, De Maria G, Brugaletta S, Montone RA, Vergallo R, Benenati S, Magnani G, D'Amario D, Porto I, Burzotta F, Abbate A, Angiolillo DJ, Crea F. Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction. Nat Rev Cardiol. 2024;21(5):283-298. Erratum in: Nat Rev Cardiol. 2024;21(5):347.
European Society of Cardiology. Cardioprotective drugs [Internet]. 2017. Disponible en: https://www.escardio.org/Education/ESCPrevention-of-CVD-Programme/Treatment-goals/Cardio-Protective-drugs [citado 2025 Mar 19].
Rouleau J. Decreasing the Risk of Heart Failure in a Changing Post-Myocardial Infarction Environment. N Engl J Med. 2024;390(16):1524-1526.
Kübler W, Haass M. Cardioprotection: definition, classification, and fundamental principles. Heart. 1996;75(4):330-3.
Tong C, Zhou B. Cardioprotective strategies in myocardial ischemia-reperfusion injury: Implications for improving clinical translation. J Mol Cell Cardiol Plus. 2024;11:100278.
Heusch G. Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol. 2020;17(12):773-789.
Hausenloy DJ, Kharbanda RK, Møller UK, Ramlall M, Aarøe J, Butler R, Bulluck H, Clayton T, Dana A, Dodd M, Engstrom T, Evans R, Lassen JF, Christensen EF, Garcia-Ruiz JM, Gorog DA, Hjort J, Houghton RF, Ibanez B, Knight R, Lippert FK, Lønborg JT, Maeng M, Milasinovic D, More R, Nicholas JM, Jensen LO, Perkins A, Radovanovic N, Rakhit RD, Ravkilde J, Ryding AD, Schmidt MR, Riddervold IS, Sørensen HT, Stankovic G, Varma M, Webb I, Terkelsen CJ, Greenwood JP, Yellon DM & Bøtker HE; CONDI-2/ERIC-PPCI Investigators. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet. 2019;394(10207):1415-1424.
Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015;373(15):1408-17.
Joshi SS, Singh T, Newby DE, Singh J. Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure. Heart. 2021 Jun 11;107(13):1032-1038. doi: 10.1136/heartjnl-2020-318060. Erratum in: Heart. 2021 Nov;107(22):e15. doi: 10.1136/heartjnl-2020-318060corr1. PMID: 33637556; PMCID: PMC8223636.
Zelniker TA, Braunwald E. Mechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2 Inhibitors: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(4):422-434. Erratum in: J Am Coll Cardiol. 2020;76(12):1505.
McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; 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.
Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424.
Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461.
Butler J, Jones WS, Udell JA, Anker SD, Petrie MC, Harrington J, Mattheus M, Zwiener I, Amir O, Bahit MC, Bauersachs J, Bayes-Genis A, Chen Y, Chopra VK, Figtree G, Ge J, Goodman SG, Gotcheva N, Goto S, Gasior T, Jamal W, Januzzi JL, Jeong MH, Lopatin Y, Lopes RD, Merkely B, Parikh PB, Parkhomenko A, Ponikowski P, Rossello X, Schou M, Simic D, Steg PG, Szachniewicz J, van der Meer P, Vinereanu D, Zieroth S, Brueckmann M, Sumin M, Bhatt DL, Hernandez AF. Empagliflozin after Acute Myocardial Infarction. N Engl J Med. 2024;390(16):1455-1466.
von Lewinski D, Kolesnik E, Tripolt NJ, Pferschy PN, Benedikt M, Wallner M, Alber H, Berger R, Lichtenauer M, Saely CH, Moertl D, Auersperg P, Reiter C, Rieder T, Siller-Matula JM, Gager GM, Hasun M, Weidinger F, Pieber TR, Zechner PM, Herrmann M, Zirlik A, Holman RR, Oulhaj A, Sourij H. Empagliflozin in acute myocardial infarction: the EMMY trial. Eur Heart J. 2022;43(41):4421-4432.
Lim VG, Bell RM, Arjun S, Kolatsi-Joannou M, Long DA, Yellon DM. SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart. JACC Basic Transl Sci. 2019;4(1):15-26.
Nikolaou PE, Konijnenberg LSF, Kostopoulos IV, Miliotis M, Mylonas N, Georgoulis A, Pavlidis G, Kuster CTA, van Reijmersdal VPA, Luiken TTJ, Agapaki A, Roverts R, Orologas N, Grigoriadis D, Pallot G, Boucher P, Kostomitsopoulos N, Pieper MP, Germain S, Loukas Y, Dotsikas Y, Ikonomidis I, Hatzigeorgiou AG, Tsitsilonis O, Zuurbier CJ, Nijveldt R, van Royen N, Andreadou I. Empagliflozin in Acute Myocardial Infarction Reduces No-Reflow and Preserves Cardiac Function by Preventing Endothelial Damage. JACC Basic Transl Sci. 2024 Aug 30;10(1):43-61.
Heusch G, Kleinbongard P. The Enigmata of Cardioprotection With SGLT2 Inhibition. JACC Basic Transl Sci. 2025;10(1):62-64.
Reed J, Kanamarlapudi V, Bain S. Mechanism of cardiovascular disease benefit of glucagon-like peptide 1 agonists. Cardiovasc Endocrinol Metab. 2018;7(1):18-23.
Wang JY, Wang QW, Yang XY, Yang W, Li DR, Jin JY, Zhang HC, Zhang XF. GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach. Front Endocrinol (Lausanne). 2023;14:1085799.
Drucker DJ. The Cardiovascular Biology of Glucagon-like Peptide-1. Cell Metab. 2016;24(1):15-30.
Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232.
Deanfield J, Verma S, Scirica BM, Kahn SE, Emerson SS, Ryan D, Lingvay I, Colhoun HM, Plutzky J, Kosiborod MN, Hovingh GK, Hardt-Lindberg S, Frenkel O, Weeke PE, Rasmussen S, Goudev A, Lang CC, Urina-Triana M, Pietilä M, Lincoff AM; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10454):773-786.
Zhu Q, Luo Y, Wen Y, Wang D, Li J, Fan Z. Semaglutide inhibits ischemia/reperfusion-induced cardiomyocyte apoptosis through activating PKG/PKCε/ERK1/2 pathway. Biochem Biophys Res Commun. 2023;647:1-8.
Liu Y, Li Z, Xu X, Zou Y, Zhang M, Chen Y, Zhu W, Han B. Semaglutide attenuates myocardial ischemia-reperfusion injury by inhibiting ferroptosis of cardiomyocytes via activation of PKC-S100A9 axis. Front Pharmacol. 2025;16:1529652.
Li L, Jin L, Tian Y, Wang J. Semaglutide enhances PINK1/Parkin dependent mitophagy in hypoxia/reoxygenation induced cardiomyocyte injury. Mol Med Rep. 2025;31(5):111.
Stone C, Harris DD, Broadwin M, Kanuparthy M, Nho JW, Yalamanchili K, Hamze J, Abid MR, Sellke FW. Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2025;45(2):285-297.
Sequeira V, Theisen J, Ermer KJ, Oertel M, Xu A, Weissman D, Ecker K, Dudek J, Fassnacht M, Nickel A, Kohlhaas M, Maack C, Dischinger U. Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of high fat diet-induced obesity. ESC Heart Fail. 2025;12(2):1386-1397.
Krammer T, Baier MJ, Hegner P, Zschiedrich T, Lukas D, Wolf M, Le Phu C, Lutz V, Evert K, Kozakov K, Li J, Holzamer A, Maier LS, Provaznik Z, Bers DM, Wagner S, Mustroph J. Cardioprotective effects of semaglutide on isolated human ventricular myocardium. Eur J Heart Fail. 2025;27(7):1315-1325.
Aird WC. Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res. 2007;100(2):174-90.
Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D'Antoni ML, Debuque R, Chandran A, Wang L, Arora K, Rosenthal NA, Tallquist MD. Revisiting Cardiac Cellular Composition. Circ Res. 2016 Feb 5;118(3):400-9.
Hsieh PC, Davis ME, Lisowski LK, Lee RT. Endothelial-cardiomyocyte interactions in cardiac development and repair. Annu Rev Physiol. 2006;68:51-66.
Strijdom H, Lochner A. Cardiac endothelium: More than just a barrier. SA Heart J. 2017;6(3):174–185.
Haybar H, Shahrabi S, Rezaeeyan H, Shirzad R, Saki N. Endothelial Cells: From Dysfunction Mechanism to Pharmacological Effect in Cardiovascular Disease. Cardiovasc Toxicol. 2019;19(1):13-22.
Menghini R, Casagrande V, Rizza S, Federici M. GLP-1RAs and cardiovascular disease: is the endothelium a relevant platform? Acta Diabetol. 2023;60(11):1441-1448.
McLean BA, Wong CK, Kabir MG, Drucker DJ. Glucagon-like Peptide-1 receptor Tie2+ cells are essential for the cardioprotective actions of liraglutide in mice with experimental myocardial infarction. Mol Metab. 2022;66:101641.
Helmstädter J, Frenis K, Filippou K, Grill A, Dib M, Kalinovic S, Pawelke F, Kus K, Kröller-Schön S, Oelze M, Chlopicki S, Schuppan D, Wenzel P, Ruf W, Drucker DJ, Münzel T, Daiber A, Steven S. Endothelial GLP-1 (Glucagon-Like Peptide-1) Receptor Mediates Cardiovascular Protection by Liraglutide In Mice With Experimental Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2020;40(1):145-158.
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