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Sodium-glucose cotransporter-2 inhibitors in heart failure : mechanisms and effects in patients with and without type 2 diabetes mellitus
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Apesar dos avanços notáveis no tratamento da insuficiência cardíaca (IC), esta continua a ser uma das principais causas de mortalidade e de morbilidade nas sociedades ocidentais. Os inibidores do co-transportador de sódio e glucose 2 (iSGLT2), uma nova classe terapêutica projetada inicialmente para reduzir a glicémia em doentes com diabetes mellitus do tipo 2 (DM2), emergiram como uma abordagem terapêutica promissora na IC. Os ensaios clínicos de segurança cardiovascular (ECSC) mostraram que os iSGLT2 reduziram consistentemente e de modo significativo os internamentos por IC em doentes com DM2. Estes resultados geraram uma intensa investigação no sentido de elucidar os mecanismos subjacentes a este efeito. No mesmo sentido, os iSGLT2 reduziram a progressão de doença renal nos ensaios clínicos. Recentemente a evidência clínica e a farmacologia dos iSGLT2 sugerem que a proteção cardio-renal conferida por estes fármacos é independente do seu efeito sobre a glicemia. Este percurso de investigação clínica culminou na realização de ensaios clínicos em doente com IC com e sem DM2, tendo sido confirmado o seu efeito terapêutico independente da diabetes. Esta revisão abrangente sumariza a evidência clínica e os dados de segurança que apoiam a utilização dos iSGLT2 na IC e procura esclarecer os efeitos hemodinâmicos, metabólicos e celulares subjacentes à proteção demonstrada pelos iSGLT2 nesta patologia, independentemente da presença de DM2.
Despite remarkable advances in clinical management, Heart Failure remains a major cause of mortality and morbidity in developed countries. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class originally designed as a glucoselowering agent to treat type 2 diabetes mellitus (T2DM), have emerged as promising therapeutic approach for HF patients. Cardiovascular outcome trials (CVOTs) have shown that SGLT2i consistently and significantly reduce hospitalizations for HF in patients with T2DM. These findings have led to an intense research to elucidate the mechanisms underlying such unexpected. In the same way, SGLT2i reduced the progression of kidney disease in CVOTs. More recently, clinical evidence and pharmacology of SGLT2i have suggested that the cardiorenal protection derived from these drugs is independent of glycemic control. This clinical research pathway has culminated in clinical trials of SGLT2i in patients with or without DM, having thus confirmed its therapeutic effects independently of T2DM. This comprehensive review summarizes clinical evidence and safety data that supports the use of SGLT2i in HF, shedding light to the current understanding of the haemodynamic, metabolic and cellular effects of SGLT2i on the failing heart.
Despite remarkable advances in clinical management, Heart Failure remains a major cause of mortality and morbidity in developed countries. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class originally designed as a glucoselowering agent to treat type 2 diabetes mellitus (T2DM), have emerged as promising therapeutic approach for HF patients. Cardiovascular outcome trials (CVOTs) have shown that SGLT2i consistently and significantly reduce hospitalizations for HF in patients with T2DM. These findings have led to an intense research to elucidate the mechanisms underlying such unexpected. In the same way, SGLT2i reduced the progression of kidney disease in CVOTs. More recently, clinical evidence and pharmacology of SGLT2i have suggested that the cardiorenal protection derived from these drugs is independent of glycemic control. This clinical research pathway has culminated in clinical trials of SGLT2i in patients with or without DM, having thus confirmed its therapeutic effects independently of T2DM. This comprehensive review summarizes clinical evidence and safety data that supports the use of SGLT2i in HF, shedding light to the current understanding of the haemodynamic, metabolic and cellular effects of SGLT2i on the failing heart.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2020
Palavras-chave
Insuficiência cardíaca Diabetes mellitus tipo 2 Inibidores do co-transportador de sódio e glucose 2