Evidência molecular e clínica do benefício cardiovascular dos inibidores de SGLT2: estado da arte
Barra lateral de artigos
Como Citar
Detalhes do artigo
Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Conteúdo do artigo principal
Resumo
O diabetes mellitus (dm) é uma doença crônica com alta incidência e prevalência. A doença é um problema de saúde pública que tem motivado a busca contínua por medidas de controle farmacológico e não farmacológico. Graças às evidências atuais, sabe-se que o dm, além dos níveis elevados de glicose no sangue, é acompanhado por otros problemas metabólicos como obesidade, alterações no metabolismo lipídico, entre outros; Além do exposto, os pacientes estão em risco de problemas cardiovasculares. O problema é que um grande número de pacientes com risco cardiovascular (CV) ou patologia cardiovascular já estabelecida sofre de diabetes mellitus. A relação entre dm e patologias cardiovasculares é de extrema importância, pois cada uma aumenta o risco de sofrer uma da outra e piora o prognóstico. Entre 1980 e 1990, o co-transportador sódio-glicose 2 (SGLT2) foi identificado como alvo para o tratamento do DM tipo 2. Com base nessa descoberta, foram criados os inibidores de SGLT2 (i-SGLT2), um novo grupo de drogas que reduzem a glicose níveis. Além disso, eles têm múltiplos efeitos micro e macrovasculares (empagliflozina, canagliflozina e dapagliflozina). Portanto, revisaremos as evidências do iSGLT2 como tratamento para insuficiência cardíaca crónica e seu impacto positivo no sistema renal, redução da pressão arterial, perda de peso, entre outros benefícios.
Referências
Rosas J, Rosas J, Romero AR. Inhibidores de SGLT2 en el tratamiento de la diabetes mellitus. Revista de la ALAD, 2015; 5:(1):14-22.
Fuster V, Ibáñez B. Diabetes y enfermedad cardiovascular. Revista Española de Cardiología Suplementos, 2008; 8(3):35C-44C.
Wilcox T, De Block C, Schwartzbard AZ, Newman JD. Diabetic agents, from metformin to SGLT2 inhibitors and GLP1 receptor agonists: JACC Focus Seminar. J Am Coll Cardiol. 2020; 75(16):1956–74.
Donahoe SM, Stewart GC, McCabe CH. Diabetes and mortality following acute coronary syndromes. JAMA. 2007; 298:765-75.
Del Olmo-Garcia MI, Merino-Torres JF. GLP-1 receptor agonists and cardiovascular disease in patients with type 2 diabetes. J Diabetes Res. 2018; 2018:4020492.
Zoungas S, Arima H, Gerstein HC. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: A meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 2017; 5:431-7.
Dalama B, Mesa J. Nuevos hipoglucemiantes orales y riesgo cardiovascular. Cruzando la frontera metabólica. Rev Esp Cardiol. 2016; 69(11):1088–97.
Zou CY, Liu XK, Sang YQ, Wang B, Liang J. Effects of SGLT2 inhibitors on cardiovascular outcomes and mortality in type 2 diabetes: A meta-analysis. Medicine. 2019; 98(49):e18245.
Pérez G, González O, Cano M. Sodium-glucos cotransporter type 2 inhibitors (SGLT2): From familial renal glucosuria to the treatment of type 2 diabetes mellitus. Nefrologia. 2010; 30(6):618–25.
Boorsma EM, ter Maaten JM, Damman K. Congestion in heart failure: A contemporary look at physiology, diagnosis and treatment. Nat Rev Cardiol. 2020: 17(10):641-655.
Buitrago AF, Sánchez CA. Mecanismos de acción de los inhibidores de cotransportador de sodio y glucosa tipo 2 —SGLT2—: Más allá del control de la glicemia. Rev Colomb Cardiol. 2020;27:22–5.
Benzing T, Salant D. Insights into glomerular filtration and albuminuria. N Engl J Med. 2021; 384(15):1437–46.
Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2020; 75(4):422–434.
Dekkers CCJ, Petrykiv S, Laverman GD, Cherney DZ, Gansevoort RT, Heerspink HJL. Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers. Diabetes Obes Metab. 2018; 20(8):1988–9.
Xie X, Atkins E, Lv J. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016; 387:435-43.
Sharma A, Verma S. Mechanisms by which glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce cardiovascular risk in adults with type 2 diabetes mellitus. Can J Diabetes. 2020; 44(1):93–102.
Baartscheer A, Schumacher CA, Wüst RCI, Fiolet JWT, Stienen GJM, Coronel R, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/ H+ exchanger in rats and rabbits. Diabetologia. 2017; 60(3):568–73.
Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, Garcia-Ropero A, Mancini D, Pinney S, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2021; 77(3):243–55.
Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013; 27:473–8.
Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue lowgrade inflammation: The potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab. 2018; 44:457-64.
Inzucchi SE, Kosiborod M, Fitchett D. Improvement in cardiovascular outcomes with empagliflozin is independent of glycemic control. Circulation 2018; 138:1904-7.
Lim GB. Beneficios de la farmacoterapia combinada para HFrEF. Reseñas de la naturaleza. Cardiología. 2020; 17(8):455.
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(22):2117–28.
Sarafidis PA, Tsapas A. Empagliflozin. Cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2016; 374(11):1092.
McGuire DK, Shih WJ, Cosentino F, Charbonnel B, Cherney DZI, Dagogo-Jack S, et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: A meta-analysis. JAMA Cardiol. 2021; 6(2):148–58.
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):1413–1424.
Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the emperor-Reduced and DAPA-HF trials. Lancet. 2020; 396(10254):819–829.
Packer M, Butler J, Filippatos G. Design of a prospective patient-level pooled analysis of two parallel trials of empagliflozin in patients with established heart failure. Eur J Heart Fail. 2020; 22:2393-8.
Butler J, Anker SD, Filippatos G, Khan MS, Ferreira JP, Pocock SJ, et al. Empagliflozin and healthrelated quality of life outcomes in patients with heart failure with reduced ejection fraction: the emperor-Reduced trial. Eur Heart J. 2021; 42(13):1203–12.
Anker SD, Butler J, Filippatos G. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021; 385(16):1451-1461.
McMurray J, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381(21):1995– 2008.
Jensen J, Omar M, Kistorp C, Gustafsson F, Køber L, Møller JE, et al. Sodium-Glucose cotransporter-2 inhibitors in heart failure with reduced ejection fraction: Current evidence and future perspectives. Basic Clin Pharmacol Toxicol. 2022; 10.1111/bcpt.13739.
Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019; 380(4):347–357.
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.
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):1436-1446.
Dziuba J, Alperin P, Racketa J, Iloeje U, Goswami D, Hardy E, et al. Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes. Diabetes Obes Metab. 2014; 16:628–35.
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377(7):644–57.
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(24):2295–306.
Neuen BL, Young T, Heerspink H, Neal B, Perkovic V, Billot L, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: A systematic review and metaanalysis. Lancet Diabetes & endocrinology. 2019; 7(11):845–854.
Wanner C, Inzucchi SE, Lachin JM. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016; 375:323-34.
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink H, Charytan dm, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019; 380(24):2295–2306.
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377(7):644–657.
Mudaliar S, Polidori D, Zambrowicz B, Henry RR. Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport: From bench to bedside. Diabetes Care. 2015; 38:2344–53.
Stratton IM, Adler AI, Neil HA. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000; 321:405-12.
Vaduganathan M, Claggett BL, Jhund PS. Estimating lifetime benefits of comprehensive diseasemodifying pharmacological therapies in patients with heart failure with reduced ejection fraction: A comparative analysis of three randomised controlled trials. Lancet. 2020; 396:121-8.
Wu JH, Foote C, Blomster J. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: A systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016; 4:411-9.
Scheen AJ. SGLT2 inhibition: Efficacy and safety in type 2 diabetes treatment. Expert Opin Drug Saf. 2015; 29:1–26.
Pascual-Figal DA, Ferrero-Gregori A, Gomez-Otero I. Mid-range left ventricular ejection fraction: Clinical profile and cause of death in ambulatory patients with chronic heart failure. Int J Cardiol. 2017; 240:265-70.
Fitchett DH, Udell JA, Inzucchi SE. Heart failure outcomes in clinical trials of glucose-lowering agents in patients with diabetes. Eur J Heart Fail. 2017; 19:43-53.
Levey AS, Stevens LA, Schmid CH. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150:604-12.
Nathan DM, Cleary PA, Backlund J-YC. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353:2643–53.
Stratton IM. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000; 321:405–12.
Trevor AJ, Katzung BG, Masters SB. Katzung’s and Trevor’s pharmacology: Examination and board review. 6th ed. Stamford, CT: Appleton & Lange; 2001.
Katzung BG. Basic and clinical pharmacology. 6th ed. Stamford, CT: Appleton and Lange; 1995.
Knollmann B, Brunton L, Hilal-Dandan R. Goodman and Gilman’s the pharmacological basis of therapeutics. 13th ed. Columbus, OH: McGraw-Hill Education; 2017.
Ficha tecnica invokana 300 mg comprimidos recubiertos con pelicula [internet]. aemps.es. [citado 2022 mar 20]. disponible en: https://cima.aemps.es/cima/dochtml/ft/113884006/ ft_113884006.html
Ficha tecnica forxiga 10 mg comprimidos recubiertos con pelicula [internet]. aemps.es. [citado 2022 mar 20]. disponible en: https://cima.aemps.es/cima/dochtml/ft/112795007/ ft_112795007.html
Ficha tecnica jardiance 10 mg comprimidos recubiertos con pelicula [internet]. aemps.es. [citado 2022 mar 20]. disponible en: https://cima.aemps.es/cima/dochtml/ft/114930014/ ft_114930014.html