[Evidence of iSGLT2 in the treatment of chronic kidney disease]. / Evidencias de los iSGLT2 en el tratamiento de la enfermedad renal crónica.

The prevalence and incidence of chronic kidney disease (CKD) is constantly on the rise and it is foreseeable that in the coming decades it will be the main chronic disease in the developed world. CKD is also one of the main causes of cardiovascular morbidity and mortality, with cardiovascular diseases being the main etiology of CKD, so that one and the other feed back into what is known as the cardiorenal axis. Until five years ago, the only pharmacological treatment that had been shown to modify the course of the disease were inhibitors of the renin angiotensin system. However, in recent years, the development of inhibitors of the sodium glucose cotransporter type2 have led to a revolution in cardiovascular and renal protection, both in diabetic and non-diabetic patients, constituting, at present, the cornerstone in the CKD management.

[Clinical and practical management of sodium-glucose cotransporter type 2 inhibitors in patients with chronic kidney disease]. / Manejo clínico-práctico de los inhibidores del cotransportador sodio-glucosa tipo 2 en pacientes con enfermedad renal crónica.

The discovery of the nephroprotective role of sodium-glucose cotransporter type 2 (iSGLT2) inhibitor drugs in people with type 2 diabetes mellitus (DM 2) following the results obtained in the respective cardiovascular safety trials led to a change in the approach to diabetic kidney disease in recent years, positioning this group in the first step in the treatment of this comorbidity. The publication of the results of the DAPA-CKD study with dapagliflozin, demonstrating its benefit in slowing the progression of chronic kidney disease (CKD) in patients with and without DM, has opened a new age in the management of this pathology. These drugs are also safe and easy to use for the clinician. This article reviews the management of iSGLT2 in patients with diabetic and non-diabetic CKD.

Reacciones adversas de los inhibidores del cotransportador sodio-glucosa tipo 2 en personas con diabetes mellitus

Introducción: Las bondades que ofrece el uso de los inhibidores del cotransportador sodio-glucosa tipo 2 en el tratamiento de la diabetes mellitus, se reportan preocupantes eventos y reacciones adversas por el empleo de este grupo de medicamentos. De ahí, la necesidad de su conocimiento por parte de los facultativos. Objetivo: Mencionar las reacciones adversas a medicamentos más frecuentes de los inhibidores del cotransportador sodio-glucosa tipo 2 en personas con diabetes mellitus. y describir aquellas de mayor interés clínico por su gravedad. Métodos: La información se obtuvo en el trimestre octubre-diciembre de 2020. Se evaluaron diferentes artículos de revisión, de investigación y páginas Web, en general tenían menos de 10 años de publicados, en idioma español, portugués o inglés. Se utilizó como motores de búsqueda de información científica a Google Académico, Pubmed y SciElo. Fueron utilizadas como palabras claves: inhibidores del cotransportador sodio-glucosa tipo 2; tratamiento; reacciones adversas; y diabetes mellitus. Fueron excluidos los artículos que no reunían las condiciones señaladas. Esto permitió el estudio de 88 artículos, de los cuales 50 fueron referenciados. Conclusiones: Los inhibidores del cotransportador sodio-glucosa tipo 2, pueden producir variadas reacciones adversas -descritas en el texto-, que de manera potencial pueden aumentar la morbilidad y mortalidad. Su uso ofrece la posibilidad de reacciones adversas graves de interés clínico, entre las que se describen: cetoacidosis diabética euglucémica, insuficiencia renal aguda, riesgo de amputaciones de los pies y fascitis necrosante del perineo.

Introduction: The benefits offered by the use of sodium-glucose cotransporter type 2 inhibitors in the treatment of diabetes mellitus, worrisome adverse events and reactions are reported for the use of this group of drugs. Hence, the need for physicians to be aware of them. Objective: To describe the most frequent adverse drug reactions of sodium-glucose cotransporter type 2 inhibitors in people with diabetes mellitus and those of greatest clinical interest due to their severity. Methods: The information was obtained in the October-December 2020 quarter. Different review articles, research articles and Web pages were evaluated, generally less than 10 years old, in Spanish, Portuguese or English. Google Scholar, Pubmed and SciElo were used as search engines for scientific information. The following keywords were used: sodium-glucose cotransporter type 2 inhibitors; treatment; adverse reactions; and diabetes mellitus. Articles that did not meet the indicated conditions were excluded. This allowed the study of 88 articles, of which 50 were referenced. Conclusions: Type 2 sodium-glucose cotransporter inhibitors can produce various adverse reactions -described in the text-, which can potentially increase morbidity and mortality. Their use offers the possibility of serious adverse reactions of clinical interest, among which the following are described: euglycemic diabetic ketoacidosis, acute renal failure, risk of foot amputations and necrotizing fasciitis of the perineum.

Diabetes e insuficiencia cardiaca. ¿Son los inhibidores del cotransportador de sodioglucosa tipo dos el futuro del tratamiento? / Diabetes and heart failure. Are type two sodium-glucose cotransporter inhibitors the future of treatment?

Introducción: La diabetes mellitus es una enfermedad metabólica cuya incidencia y prevalencia van en aumento. Produce múltiples complicaciones tales como enfermedad aterosclerótica e insuficiencia cardiaca, siendo esta última, una de las principales causas de muerte. La diabetes mellitus puede desembocar en insuficiencia cardiaca a través de la miocardiopatía diabética.Para el tratamiento de la misma, destacan los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2), fármacos que actúan en el túbulo contorneado proximal renal. Objetivos: conocer el impacto de los iSGLT2 en el tratamiento de la diabetes mellitus con insuficiencia cardiaca asociada, identificar los mecanismos que relacionan diabetes mellitus e insuficiencia cardiaca y conocer el manejo de este tipo de pacientes. Resultados y discusión: Los estudios de seguridad cardiovascular EMPAREG-OUTCOME, CANVAS DECLARE-TIMI 58 y CREDENCE, han demostrado que empagliflozina, canagliflozina y dapagliflozina disminuyen el riesgo de eventos cardiovasculares mayores, muerte por causa cardiovascular y reducen el porcentaje de hospitalizaciones por insuficiencia cardiaca. Su mecanismo de acción no está del todo claro, no obstante, sus efectos glucosúricos y natriuréticos resultan potencialmente beneficiosos sobre la presión arterial, peso corporal, remodelado cardiaco y función renal. Estos estudios también señalan la importancia de conocer los efectos secundarios y monitorizarlos para prevenirlos, que, aunque infrecuentes, pueden ocasionar infecciones o amputaciones. Conclusion: essegún la evidencia actual, los iSGLT2 constituyen la mejor opción terapéutica en pacientes con diabetes e insuficiencia cardiaca concomitante y aquellos con enfermedad renal crónica (FG entre 30-60 ml/min/1,73 m2), recomendándose además su empleo en aquellos pacientes con insuficiencia cardiaca sin diabetes.(AU)

Introduction: Diabetes mellitus is a metabolic disease whose incidence and prevalence are increase. It produces multiple complications such as atherosclerotic disease and cardiac insufficiency, heart disease, the latter being one of the main causes of death. Diabetes mellitus can lead to heart failure through diabetic cardiomyopathy. For its treatment, sodium-glucose cotransporter type 2 inhibitors stand out. (iSGLT2), drugs that act on the renal proximal convoluted tubule. Objective: to know the impact of iSGLT2 in the treatment of diabetes mellitus with nsufficiency associated heart failure, identify the mechanisms that relate diabetes mellitus and heart failure and know the management of this type of patients. Results and Discussion: Cardiovascular safety studies EMPAREG-OUTCOME, CANVAS DECLARE-TIMI 58 and CREDENCE have shown that empagliflozin, canagliflozin, and dapagliflozin they reduce the risk of major cardiovascular events, death due to cardiovascular causes and reduce the percentage of hospitalizations for heart failure. Its mechanism of action is not entirely clear, however, its glycosuric and natriuretic effects are potentially beneficial on the blood pressure, body weight, cardiac remodeling and renal function.These studies also point out the importance of knowing side effects and monitoring them to prevent them, which, although rare, can cause infections or amputations. Conclusion: saccording to current evidence, iSGLT2 constitute the best therapeutic option in patients with diabetes and concomitant heart failure and those with chronic kidney disease (GFR between 30-60 ml/min/1.73 m2), also recommending its use in those patients with heart failure without diabetes.(AU)

Uso de empagliflozina en pacientes diabéticos tipo 2 con insuficiencia cardíaca

Resumen: Introducción: La insuficiencia cardíaca es una patología con alta prevalencia y morbimortalidad. Entre las estrategias terapéuticas se debe considerar el abordaje de las comorbilidades, entre ellas la diabetes mellitus tipo 2. Los pacientes con insuficiencia cardíaca que la asocian, tienen 75% más riesgo de hospitalización y mortalidad. La Food and Drug Administration ha enfatizado desde 2008 que todo nuevo hipoglucemiante debe tener un efecto beneficioso o al menos neutro a nivel cardiovascular. Varios estudios han demostrado que los inhibidores del cotransportador sodio glucosa tipo 2 (empagliflozina, canagliflozina y dapagliflozina) cumplen con estos requerimientos. El objetivo de este trabajo es describir la experiencia en "vida real" de la empagliflozina en pacientes con diabetes mellitus 2 e insuficiencia cardíaca con fracción de eyección reducida. Metodología: Se realizó un estudio prospectivo, longitudinal, entre julio 2019 - abril 2021 en una Unidad Multidisciplinaria de Insuficiencia Cardíaca. Resultados: Se incluyeron 25 pacientes Se incluyeron 25 pacientes (13 hombres) con edad media 61 años. La dosis objetivo de empagliflozina se alcanzó en el 95% de los pacientes. Se observó un descenso de peso, hemoglobina glicosilada y glicemia de ayunas. Conclusiones: La empagliflozina presentó buena tolerabilidad, con efectos beneficiosos a nivel cardiovascular y mínimos efectos adversos.

Abstract: Introduction: Heart failure is a pathology with high prevalence and morbidity and mortality. Among the therapeutic strategies, addressing comorbidities should be considered, including type 2 diabetes mellitus. Patients with associated heart failure have a 75% higher risk of hospitalization and mortality. The Food and Drug Administration has emphasized since 2008 that all new hypoglycemic agents must have a beneficial or at least neutral effect at the cardiovascular level. Several studies have shown that sodium-glucose cotransporter 2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin) meet these requirements. The objective of this work is to describe the "real life" experience of empagliflozin in patients with type 2 diabetes mellitus and heart failure with reduced ejection fraction. Methodology: A prospective, longitudinal study was carried out between July 2019 and April 2021 in a Multidisciplinary Heart Failure Unit. Results: Twenty-five patients (13 men) with a mean age of 61 years were included. The target dose of empagliflozin was achieved in 95% of patients. A decrease in weight, glycosylated hemoglobin and fasting blood glucose was observed. Conclusions: Empagliflozin presented good tolerability, with beneficial effects at the cardiovascular level and minimal adverse effects.

Resumo: Introdução: A insuficiência cardíaca é uma patologia com alta prevalência e morbidade e mortalidade. Dentre as estratégias terapêuticas, deve-se considerar a abordagem de comorbidades, incluindo diabetes mellitus tipo 2. Pacientes com insuficiência cardíaca associada apresentam risco 75% maior de hospitalização e mortalidade. A Food and Drug Administration tem enfatizado desde 2008 que todos os novos agentes hipoglicemiantes devem ter um efeito benéfico ou pelo menos neutro no nível cardiovascular. Vários estudos mostraram que os inibidores do cotransportador 2 de sódio-glicose (empagliflozina, canagliflozina e dapagliflozina) atendem a esses requisitos. O objetivo deste trabalho é descrever a experiência da "vida real" da empagliflozina em pacientes com diabetes mellitus tipo 2 e insuficiência cardíaca com fração de ejeção reduzida. Metodologia: Foi realizado um estudo prospectivo, longitudinal, entre julho de 2019 e abril de 2021 em uma Unidade Multidisciplinar de Insuficiência Cardíaca. Resultados: Vinte e cinco pacientes (13 homens) com idade média de 61 anos foram incluídos. A dose alvo de empagliflozina foi alcançada em 95% dos pacientes. Observou-se diminuição do peso, da hemoglobina glicosilada e da glicemia de jejum. Conclusões: A empagliflozina apresentou boa tolerabilidade, com efeitos benéficos a nível cardiovascular e efeitos adversos mínimos.

Rol de nuevos fármacos antidiabéticos en prevención cardiovascular e insuficiencia cardiaca / Role of newer antidiabetic drugs on cardiovascular prevention and heart failure

Más allá del control de la glucemia existen otros objetivos importantes a la hora de brindar atención integral a pacientes con diabetes mellitus. Se realizó una revisión bibliográfica con el objetivo de identificar el papel que desempeñan los nuevos fármacos antidiabéticos en la prevención cardiovascular y la insuficiencia cardiaca. El uso de SGLT2i y GLP-1a acarrea una disminución significativa de eventos cardiovasculares, sin diferencias entre ambos, exceptuando las hospitalizaciones por insuficiencia cardiaca, en donde es evidente la superioridad de estos últimos (en especial dapaglifozina y empaglifozina). La evidencia actual respecto al efecto de los DPP-4i es diversa, aunque se observa un aumento del riesgo de hospitalizaciones por insuficiencia cardiaca con el consumo de algunos fármacos de esta clase (saxagliptina).(AU)

Beyond glucemic control there are other important goals when it comes to providing integral care to patients with diabetes mellitus. A bibliographic review was made in order to identify the role played by new antidiabetic drugs in cardiovascular prevention and heart failure. The use of SLGT2i and GLP1a leads to a significant decrease in cardiovascular events, with no difference between the two, except when it comes to hospitalizations for heart failure, where the superiority of the last ones (especially dapaglifozin and empaglifozin) is evident. The current evidence regarding the effect of dpp-4i is diverse, although an increased risk of hospitalizations for heart failure is observed with the use of some drugs of this class (saxagliptin).(AU)

Inhibidores del cotransportador de sodio-glucosa tipo 2: Efecto de los mecanismos moleculares en el miocardio / Sodium-glucose cotransporter 2 inhibitors: Effect of molecular mechanisms on the myocardium

Resumen Los receptores del cotransportador de sodio-glucosa han demostrado una gran relevancia en la función miocárdica. Los receptores tipo 1 se encuentran en el miocardio en valores bajos, sin embargo, se elevan en patologías cardiacas por medio de distintos mecanismos moleculares. Por otra parte, los receptores tipo 2 están ausentes en el miocardio. Los fármacos que inhiben este receptor tienen beneficio cardiovascular evidente en estudios clínicos y experimentales, principalmente en pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca, en los que se ha demostrado una reducción de la mortalidad por causas cardiovasculares y reducción en hospitalización por insuficiencia cardiaca. Existen interrogantes sobre el mecanismo de acción directo de este grupo antihiperglicemiantes sobre el cardiomiocito y se han desarrollado hipótesis y teorías para explicar este efecto. El objetivo de este artículo es revisar y analizar los diferentes mecanismos metabólicos, estructurales, funcionales y mitocondriales en un contexto molecular de los inhibidores del cotransportador sodio-glucosa tipo 2. La acción fisiopatológica del receptor tipo 1 en el miocardio también es importante y se encuentran en desarrollo estudios clínicos para establecer el efecto de su inhibición a nivel cardíaco.

Abstract Sodium-glucose cotransporter receptors have demonstrated relevance in myocardial function. Type 1 receptors are found in the myocardium in low values, however, they are elevated in cardiac pathologies by means of different molecular mechanisms. On the other hand, type 2 receptors are absent in the myocardium. The drugs that inhibit this receptor have been shown to have a cardiovascular benefit demonstrated in clinical and experimental studies, mainly in patients with type 2 diabetes mellitus and heart failure, presenting a reduction in mortality due to cardiovascular causes and a reduction in hospitalization due to heart failure. Due to the above, many questions arise about the mechanism of direct action of this antihyperglycemic group on cardiomyocyte, which is why they have been developed from hypotheses and theories to clarify this action by medicines. The objective of this article is to analyze the different metabolic, structural, functional and mitochondrial mechanisms in a molecular context of the inhibitors of the sodium-glucose cotransporter type 2. On the other hand, to analyze the pathophysiological action of the type 1 receptor in the myocardium, since that future clinical studies will be developed to establish the effect with its inhibition at the cardiac level.

Role of newer antidiabetic drugs on cardiovascular prevention and heart failure. / Rol de nuevos fármacos antidiabéticos en prevención cardiovascular e insuficiencia cardiaca.

Beyond glucemic control there are other important goals when it comes to providing integral care to patients with diabetes mellitus. A bibliographic review was made in order to identify the role played by new antidiabetic drugs in cardiovascular prevention and heart failure. The use of SLGT2i and GLP1a leads to a significant decrease in cardiovascular events, with no difference between the two, except when it comes to hospitalizations for heart failure, where the superiority of the last ones (especially dapaglifozin and empaglifozin) is evident. The current evidence regarding the effect of dpp-4i is diverse, although an increased risk of hospitalizations for heart failure is observed with the use of some drugs of this class (saxagliptin).

El efecto de los antihiperglicemiantes en los parámetros ecocardiográficos diastólicos y sistólicos / The effect of antihyperglycemic agents on diastolic and systolic echocardiographic parameters

Resumen La enfermedad metabólica diabetes mellitus tipo 2 ocasiona alteraciones en la estructura y en la funcionalidad miocárdica por diferentes mecanismos bioquímicos los cuales pueden ocasionar disfunción diastólica y sistólica, por lo cual el uso de los antihiperglicemiantes aparte de su efecto en la reducción de la hiperglicemia y la hemoglobina glicosilada, algunos han demostrado reducción en la mortalidad cardiovascular y de las hospitalizaciones por insuficiencia cardiaca, basado en estudios clínicos sobre este impacto en el miocardio. También se ha evaluado el efecto de estos fármacos por medio del ecocardiograma transtorácico. El objetivo de este articulo es analizar los valores de los parámetros ecocardiográficos sistólicos y diastólicos en pacientes diabéticos tipo 2 o alguna cardiopatía de base como antecedente de infarto al miocardio e insuficiencia cardiaca con el uso de metformina, sulfonilureas, los inhibidores de la dipeptidilpeptidasa 4 (sitagliptina, alogliptina y linagliptina, vildagliptina), los análogos de GLP1 (liraglutide, albiglutide y exenatide).

Abstract Metabolic disease type 2 diabetes mellitus causes alterations in both structure and myocardial functionality by different biochemical mechanisms which can cause diastolic and systolic dysfunction, which is why the use of antihyperglycemic agents apart from its effect in the reduction of hyperglycemia and glycosylated hemoglobin, some groups have shown reduction in cardiovascular mortality and hospitalizations for heart failure this based on clinical studies, by hypothesis, theories and pleiotropic mechanisms on this impact on the myocardium. On the other hand, the effect of these drugs on the myocardium has also been evaluated by transthoracic echocardiography. Therefore, the aim of this article is to analyze the values of systolic and diastolic echocardiographic parameters in type 2 diabetic patients or some underlying heart disease as a history of myocardial infarction and heart failure with the use of metformin, sulfonylureas, inhibitors of the dipeptidylpeptidase 4 (sitagliptin, alogliptin and linagliptin, vildagliptin), GLP1 analogues (liraglutide, albiglutide and exenatide).

Diuretic treatment of the patient with diabetes and heart failure. Role of SGLT2 inhibitors and similarities with carbonic anhydrase inhibitors. / Tratamiento diurético del paciente con diabetes e insuficiencia cardiaca. El papel de los inhibidores de la SGLT2 y semejanzas con los inhibidores de la anhidrasa carbónica.

Sodium-glucose cotransporter-2 inhibitors have changed the concept of the effects that hypoglycemic drugs have on hearth failure (HF). For the first time, a therapeutic group has modified the evolution of HF. Its effect goes beyond glycemic control, and different theories have been postulated to justify this benefit. In the article we sent, we analyze the influence of the different pharmacological groups used in type 2 diabetes mellitus on HF, and we present the theory of the mechanism of action associated with the benefit of these drugs. In our opinion, this benefit in HF is secondary to its diuretic effect, specifically an effect very similar to carbon dioxide inhibitors. We think that our theory is novel, explains the mechanism of action and we have not found in the literature any article that explains the mechanism of action in such a precise way.

Efecto cardiometabólico de los inhibidores del cotransportador sodio glucosa tipo 2 (SGLT2) / Cardiometabolic effect of inhibitors of sodium glucose cotransporter type 2 (SGLT2)

Resumen: El advenimiento de nuevos fármacos para el tratamiento de los distintos componentes del síndrome metabólico, que por su farmacocinética y farmacodinamia tengan un efecto pleiotrópico, ha tomado auge. Hace poco los inhibidores del cotransportador sodio glucosa tipo 2 (SGLT2) prescritos para el tratamiento de la diabetes mellitus 2 han demostrado tener un efecto protector cardiorrenal. Éstos actúan en el segmento S1 del túbulo proximal disminuyendo la filtración de glucosa e incrementando su excreción urinaria; con efecto glucosúrico y natriurético. Este último es el principal mecanismo de protección cardiovascular. Modelos experimentales y estudios, entre los que destacan el estudio EMPAREG y el programa CANVAS, han demostrado que los inhibidores de SGLT2 permiten disminuir la progresión de la miocardiopatía hipertrófica, fibrosis, remodelamiento, disfunción sistólica e insuficiencia cardiaca, por su efecto en la precarga y poscarga. Los resultados de estos estudios reconocen a este grupo de fármacos (específicamente a la empagliflozina y canagliflozina) como tratamiento de protección cardiovascular en pacientes con diabetes mellitus 2, recomendados actualmente por la FDA, ACC/AHA, la Sociedad Europea de Cardiología y recientemente por la Asociación Americana de Diabetes (ADA) en su reciente publicación de 2018.

Abstract: There is an increase in the use of new drugs for the treatment of the different elements that integrate the metabolic syndrome; that, by their pharmacokinetics and pharmacodynamics have a pleiotropic effect. Recently, the inhibitors of sodium glucose cotransporter type 2 (SGLT2) used for the treatment of diabetes mellitus type 2 have demonstrated a cardio-renal protector effect. They function at the S1 segment of the proximal tube, lowering the filtration of glucose and enhancing its excretion; resulting in a glycosuric and natriuretic effect. This is the main mechanism of cardiovascular protection. Experimental essays and different studies, such as the EMAREG study and the CANVAS program, have established that the inhibitors of SGLT2 reduce the progression of hypertrophic cardiomyopathy, fibrosis, cardiac remodeling, systolic dysfunction and heart failure. The results of these studies recognize this group of drugs (empaglifozine and canaglifozine) as a valid treatment for cardiovascular protection in patients with diabetes mellitus type 2, and which is recommended by the FDA, the ACC/AHA, the European Society of Cardiology and the American Diabetes Association (ADA) in its last publication in 2018.

Uso de la dapagliflozina en el tratamiento de la diabetes mellitus tipo 2 / Use of dapagliflozin in the treatment of type 2 diabetes mellitus

Introducción: la dapagliflozina es un inhibidor del cotransportador sodio-glucosa tipo 2, un nuevo grupo de fármacos que disminuyen la glucemia, con bajo riesgo de hipoglucemia y con discreta pérdida de peso. Objetivo: describir algunos aspectos de interés sobre el uso de la dapagliflozina en el tratamiento de los pacientes con diabetes mellitus tipo 2, para lo cual, se realizó una revisión de varios artículos publicados sobre el tema, a través de algunas bases de datos y de los buscadores habituales (PubMed, Cochrane, Google, y otros), teniendo en cuenta su calidad y actualidad, según criterio de los autores. Desarrollo: la dapagliflozina es administrada por vía oral, e inhibe la reabsorción de glucosa en el túbulo proximal renal y aumenta la excreción urinaria de glucosa (efecto glucosúrico). Se utiliza a una dosis de 10 mg diarios, sola o asociada a otros medicamentos normo o hipoglucemiantes. En ambos casos es capaz de disminuir los niveles de la hemoglobina glucosilada. Su efectividad es similar a las sulfonilureas. Los efectos adversos más frecuentes se relacionan con un incremento de las infecciones genitourinarias, cetoacidosis con glucemias no tan elevadas, y cáncer. Conclusiones: la dapagliflozina es efectiva en reducir los niveles de la hemoglobina glucosilada, el peso corporal y de la presión arterial en pacientes con diabetes mellitus tipo 2, sobre todo, cuando se adiciona a otros medicamentos como la metformina. Su uso debe ser considerado como un tratamiento coadyuvante, aunque su indicación se debe individualizar, debido a su costo y sus posibles efectos adversos(AU)

Introduction: dapagliflozin is a sodium-glucose cotransporter 2 inhibitor, a new group of pharmaceuticals that reduce glycemia, with low risk of hypoglycemia and modest loss of weight. Objective: to describe some aspects of interest on the use of dapagliflozin in the treatment of patients with type 2 diabetes mellitus for which several articles published on this topic were reviewed through some databases and the regular searchers (PubMed, Cochrane, Google and others), taking into account their quality and topicality, according to the authors' criteria. Development: dapagliflozin is orally administered and inhibits the re-absorption of glucose in the renal proximal tubule and increases the urinary glucose excretion (glycosuric effect). The dose is 10 mg daily, single or combined with other normoglycemic and hypoglycemic drugs. In both cases, it is able to diminish the levels of glycosylate hemoglobin. The effectiveness of this new drug is similar to that of the sulfonylureas. The most frequent effects are related to increase in genitourinary infections, ketoacidosis with not so high glycemia values and cancer. Conclusions: dapagliflozin is effective for the reduction of levels of glycosylate hemoglobin, body weight and blood pressure in patients with type 2 diabetes mellitus, mainly when added to other drugs like metformin. It should be considered as a coadjuvant treatment, although it should be prescribed on an individual footing due to its cost and possible adverse effects(AU)

Uso de la dapagliflozina en el tratamiento de la diabetes mellitus tipo 2 / Use of dapagliflozin in the treatment of type 2 diabetes mellitus

Introducción: la dapagliflozina es un inhibidor del cotransportador sodio-glucosa tipo 2, un nuevo grupo de fármacos que disminuyen la glucemia, con bajo riesgo de hipoglucemia y con discreta pérdida de peso. Objetivo: describir algunos aspectos de interés sobre el uso de la dapagliflozina en el tratamiento de los pacientes con diabetes mellitus tipo 2, para lo cual, se realizó una revisión de varios artículos publicados sobre el tema, a través de algunas bases de datos y de los buscadores habituales (PubMed, Cochrane, Google, y otros), teniendo en cuenta su calidad y actualidad, según criterio de los autores. Desarrollo: la dapagliflozina es administrada por vía oral, e inhibe la reabsorción de glucosa en el túbulo proximal renal y aumenta la excreción urinaria de glucosa (efecto glucosúrico). Se utiliza a una dosis de 10 mg diarios, sola o asociada a otros medicamentos normo o hipoglucemiantes. En ambos casos es capaz de disminuir los niveles de la hemoglobina glucosilada. Su efectividad es similar a las sulfonilureas. Los efectos adversos más frecuentes se relacionan con un incremento de las infecciones genitourinarias, cetoacidosis con glucemias no tan elevadas, y cáncer. Conclusiones: la dapagliflozina es efectiva en reducir los niveles de la hemoglobina glucosilada, el peso corporal y de la presión arterial en pacientes con diabetes mellitus tipo 2, sobre todo, cuando se adiciona a otros medicamentos como la metformina. Su uso debe ser considerado como un tratamiento coadyuvante, aunque su indicación se debe individualizar, debido a su costo y sus posibles efectos adversos(AU)

Introduction: dapagliflozin is a sodium-glucose cotransporter 2 inhibitor, a new group of pharmaceuticals that reduce glycemia, with low risk of hypoglycemia and modest loss of weight. Objective: to describe some aspects of interest on the use of dapagliflozin in the treatment of patients with type 2 diabetes mellitus for which several articles published on this topic were reviewed through some databases and the regular searchers (PubMed, Cochrane, Google and others), taking into account their quality and topicality, according to the authors criteria. Development: dapagliflozin is orally administered and inhibits the re-absorption of glucose in the renal proximal tubule and increases the urinary glucose excretion (glycosuric effect). The dose is 10 mg daily, single or combined with other normoglycemic and hypoglycemic drugs. In both cases, it is able to diminish the levels of glycosylate hemoglobin. The effectiveness of this new drug is similar to that of the sulfonylureas. The most frequent effects are related to increase in genitourinary infections, ketoacidosis with not so high glycemia values and cancer.Conclusions: dapagliflozin is effective for the reduction of levels of glycosylate hemoglobin, body weight and blood pressure in patients with type 2 diabetes mellitus, mainly when added to other drugs like metformin. It should be considered as a coadjuvant treatment, although it should be prescribed on an individual footing due to its cost and possible adverse effects(AU)

Relevance of weight in the management of patients with type 2 diabetes mellitus: towards an adipocentric approach to diabetes. / Importancia del peso en el control del paciente con diabetes mellitus tipo 2: hacia una visión adipocéntrica del abordaje de la diabetes.

In recent decades, there has been a worldwide parallel increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given that increased visceral fat is the main risk factor for the development of T2DM in genetically predisposed individuals. An intervention focused on intensive blood glucose control in T2DM with classic drugs increases the risk of weight gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle changes, drugs and/or surgery simultaneously improves most cardiovascular (CV) risk factors, including hyperglycemia. Intensive intervention on lifestyle induces an overall benefit in patients with T2DM, but long-term weight loss is modest and has not been shown to reduce CV morbidity and mortality. The emergence of new therapeutic classes for T2DM and obesity, which simultaneously improve HbA1c, weight and other CV risk factors without inducing hypoglycaemia, represents a major change in the management of patients with diabesity. A sodium-glucose cotransporter-2 inhibitor and a GLP-1 receptor agonist have recently been shown to decrease CV and total mortality in type 2 diabetic patients with CV disease. Furthermore, bariatric surgery rapidly induces remission or improvement of T2DM in a large percentage of patients and reduces diabetes-related mortality. The emergence of new therapies raises the possibility of changing the current glucose-centred therapeutic strategy for a weight-centred approach.

[Type 2 diabetes mellitus: new treatments]. / Diabetes mellitus tipo 2: nuevos tratamientos.

The benefits and problems associated with traditional hypoglycemic drugs, such as failure of beta cells, hypoglycemia and weight gain, that lead to a worsening of diabetes, are reviewed. New hypoglycemic drugs with incretin effect (glucagon-like peptide-1 agonists and dipeptidyl peptidase 4 inhibitors), achieve, in a glucose dependent manner, an glycosylated hemoglobin reduction without hypoglycemia or increase in body weight. Recently, another group of oral hypoglycemic drugs, sodium-glucose cotransporter type 2 inhibitors, have demonstrated efficacy in diabetes control by inhibiting renal glucose reabsorption. However, long-term effects and cardiovascular prevention remain to be demonstrated. We have more and better drugs nowadays. Hypoglycemic treatment should be customized (glycosylated hemoglobin levels, risk-benefit, risk of hypoglycemia, weight changes, cardiovascular risk), with a combination of drugs being necessary in most cases. However, we do not have yet an ideal hypoglycemic drug. Moreover we must remember that an early and intensive treatment of dyslipidemia and hypertension is essential for the prevention of cardiovascular disease in patients with type 2 diabetes.

[Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and familial renal glycosuria to the treatment of type 2 diabetes mellitus]. / Inhibidores SGLT-2: de la corteza del manzano y la glucosuria familiar al tratamiento de la diabetes mellitus tipo 2.

The therapeutic armamentarium for the treatment of hyperglycemia in type 2 diabetes mellitus is still inadequate. We are currently witnessing the introduction of a new mode of hypoglycemic treatment through induction of glycosuria to decrease the availability of the metabolic substrate, i.e. glucose. Clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors are as efficacious as other oral hypoglycemic drugs. This article discusses the basic features of this new treatment concept and the efficacy and safety of this new drug group.