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Are the antidiabetic SGLT2 inhibitors a cardiovascular treatment?
¿Son los inhibidores del receptor SGLT2 fármacos antidiabéticos o cardiovasculares?
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Ariana P. Vargas Delgado, Juan Antonio Requena Ibañez
Corresponding author
, Carlos G. Santos-Gallego, Juan Jose Badimon
Atherothrombosis Research Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States
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Table 1. SGLT receptors.
Table 2. Principal clinical trials with SGLT2i.
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Abstract

The sodium-glucose co-transporter 2 inhibitors (SGLT2i) were first conceived to treat type 2 diabetes due to their hypoglycaemic effect. However, due to an increasing number of studies, SGLT2i are changing the way we treat, and understand, diabetes, and cardiovascular risk, in general.

The EMPA-REG OUTCOME clinical trial, in 2015, showed for the first time that empagliflozine-a glucose lowering agent-lowers the risk of death from cardiovascular causes and death from any cause. Also, this SGLT2i lowered hospital admission for heart failure and delayed renal function worsening. From then on, other clinical trials with SGLT2i such as CANVAS (Canagliflozin) and DECLARE-TIMI 58 (Dapagliflozin) confirmed these positive effects.

With a proven and non-related glucose-lowering effect on heart failure, overall death, cardiovascular death, and renal function, SGLT2i stands out among the rest of anti-diabetic drugs. Since its role in treating patients with heart failure and type 2 diabetes has been undoubtedly established, new studies are paving the way for non-diabetic patients as well. A potential paradigm shift is being witnessed and, probably, the dawn of a new field, cardio-endocrinology, which involves new and far-reaching pharmacological agents.

Keywords:
Cardiovascular risk
Diabetes
Heart failure
Riesgo cardiovascular
Insuficiencia cardíaca
Resumen

Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) fueron incialmente desarrollados para el tratamiento de la diabetes por su actividad hipoglucemiante. Sin embargo, a la luz de los estudios clínicos más recientes, están revolucionando el abordaje de la enfermedad cardiovascular (CV) en el paciente diabético.

En el año 2015, el ensayo clínico EMPA-REG OUTCOME nos demuestra por primera vez que la empagliflozina –un fármaco considerado «antidiabético»—reduce la mortalidad CV y por cualquier causa, además de eventos CV mayores, hospitalización por IC y progresión de enfermedad renal. Posteriormente, otros estudios clínicos con agentes del mismo grupo farmacológico, CANVAS con canagliflozina y DECLARE-TIMI-58 con dapagliflozina, corroboran la exitencia de los beneficios CV asociados a la inhibición del receptor SGLT2.

Los beneficios observados los sitúan más allá de simples agentes hipoglucemiantes, con un demostrado efecto cardionefroprotector en la enfermedad aterosclerótica, insuficiencia cardíaca, mortalidad total, mortalidad cardiovascular y progresión de insuficiencia renal. Actualmente ya son una realidad en pacientes diabéticos de alto y muy alto riesgo cardiovascular, mientras su evidencia en el paciente no diabético es cada vez mayor. Asistimos por tanto a un cambio de paradigma y posiblemente al nacimiento de una nueva especialidad, la cardio-endocrinología, con la implicación de nuevos tratamientos que deben ser considerados más que sólo fármacos antidiabéticos.

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