Comparison of baseline clinical characteristics among people with type 2 diabetes on second-line therapy previously added with dapagliflozin or another oral glucose-lowering drug: AGORA study.

INTRODUCTION: Type 2 diabetes mellitus (T2D) has acquired epidemic proportions worldwide. In recent years, new oral glucose-lowering drugs (OGLD) have emerged that improve the cardiovascular-kidney-metabolic control in T2D people. OBJECTIVES: To compare the baseline clinical-biological characteristics among T2D people to whom had added-on dapagliflozin (DAPA group) or another OGLD (SOC group) second-line hypoglycaemic therapies among the AGORA study population. METHODS: This is a multicentre cross-sectional observational study of the baseline characteristics of T2D people recruited through competitive sampling among 46 primary care health centres in Spain for the AGORA study. The inclusion and exclusion criteria of participants, and justification of the sample size are reported. After verifying the data necessary to be evaluated and informed consent, 317 subjects were included to the DAPA group and 288 to the SOC group. Both categorical and continuous variables were analysed and compared with the usual statistics. Cohen's d was used to assess the standardised difference in means. RESULTS: Six hundred and five patients with T2D were assessed (mean age 63.5 [SD±8.1] years, 61.8% men), whom 17.4% were smokers, 47.6% had obesity, 74.8% hypertension, 87.3% dyslipidaemia, and 41.7% reported physical inactivity, with no significant differences between both comparison groups. The mean (SD) evolution time of T2D was 10.1 (5.6) years. Most baseline clinical-biological characteristics at recruitment were similar in both groups. However, DAPA group was younger (2.9 years), and had lower systolic blood pressure (SBP) (2.8mmHg), higher body weight (BW) (3.7kg), and higher glycated haemoglobin A1c (HbA1c) (0.3%) than SOC group. Only 11.5% of participants had poor glycaemic control (HbA1c>8%) at recruitment, 54.9% had good glycaemic control (HbA1c<7%), being significantly lower in the DAPA group (47.3%) than in the SOC group (63.4%). The percentage of T2D patients with high vascular risk (VR) was 46.3%, and 53.7% with very high VR, being significantly higher in the DAPA group (57.4%) than in the SOC group (49.6%). CONCLUSIONS: Most baseline cardiovascular-kidney-metabolic characteristics were similar in T2D patients whom had added dapagliflozin on second-line hypoglycaemic therapy as those whom had added-on another OGLD. However, patients whom had added-on dapagliflozin had higher VR, lower SBP, higher BW, and slightly worse HbA1c control. Future research is necessary to explain the causes of these differences in cardiometabolic control.

La reducción temprana del filtrado glomerular se asocia con aumento de la hemoglobina tras el inicio de dapagliflozina en la insuficiencia cardiaca con fracción de eyección reducida / Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction

Introducción y objetivos: Los inhibidores del cotransportador 2 de sodio-glucosa (iSGLT2) inducen cambios a corto plazo en la función renal y la hemoglobina y su fisiopatología se comprende de manera incompleta. Nuestro objetivo es evaluar la relación entre los cambios de la tasa de filtrago glomerular estimado (TFGre) y la hemoglobina tras el inicio de dapagliflozina en pacientes estables con insuficiencia cardiaca y fracción de eyección reducida (IC-FEr). Métodos: Este análisis post hoc de un ensayo clínico aleatorizado evaluó el efecto de la dapagliflozina sobre el consumo máximo de oxígeno a 1 y 3 meses en pacientes ambulatorios con IC-FEr estable (ensayo DAPA-VO2, NCT04197635). Se utilizó un análisis de regresión lineal mixta para evaluar la relación entre los cambios en la TFGe y la hemoglobina a 1 y 3 meses. Resultados: Se evaluó a 87 pacientes. La media de edad era 67,0±10,5 años, y 21 pacientes (24,1%) eran mujeres. Las medias basales de TFGe y hemoglobina fueron de 66,9±20,7ml/min/1,73 m2 y 14,3±1,7g/dl respectivamente. En comparación con el placebo, la TFGe no cambió significativamente en el grupo de dapagliflozina, pero la hemoglobina aumentó significativamente a 1 y 3 meses. A 1 mes, el aumento de la hemoglobina se relacionó con la disminución de la TFGe solo en el grupo de dapagliflozina (p <0,001). A los 3 meses no había asociación significativa (p=0,123). Los cambios de la TFGe a 1 y 3 meses no se asociaron con cambios en el consumo pico de oxígeno, la calidad de vida o los péptidos natriuréticos. Conclusiones: En pacientes con IC-FEr estable, los cambios en la TFGe a 1 mes inducidos por la dapagliflozina están en relación inversa con cambios en la hemoglobina. Esta asociación no se observa a los 3 meses. (AU)

Introduction and objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF). Methods: This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO2 trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms. Results: A total of 87 patients were evaluated in this substudy. The mean age was 67.0± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9±20.7mL/min/1.73m2 and 14.3±1.7g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P <.001). At 3 months, there was no significant association in either treatment arms (P=.123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides. Conclusions: In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months. (AU)

Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS: This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO2 trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms. RESULTS: A total of 87 patients were evaluated in this substudy. The mean age was 67.0± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9±20.7mL/min/1.73m2 and 14.3±1.7g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P <.001). At 3 months, there was no significant association in either treatment arms (P=.123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides. CONCLUSIONS: In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months.

[Dapagliflozin in the prevention and treatment of heart failure]. / Dapagliflozina en la prevención y tratamiento de la insuficiencia cardiaca.

To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied in its etiopathogenesis, including not only sympathetic nervous system, and renin-angiotensin system, but also vasoactive peptides and sodium-glucose transport protein 2. The DAPA-HF trial demonstrated that the addition of dapagliflozin to the standard treatment in HF with reduced left ventricular ejection fraction, markedly decreases the risk of cardiovascular death, HF hospitalization and overall death. In addition, dapagliflozin improves functional class and quality of life. Importantly, the prognostic benefit starts early after initiating treatment with dapagliflozin, regardless baseline therapy or the presence of diabetes. All these evidences make dapagliflozin as one of the mainstays of treatment for the management of HF with reduced left ventricular ejection fraction.

[Practical approach of dapagliflozin for the treatment of heart failure. Role of primary care physician]. / Abordaje práctico de dapagliflozina en el tratamiento de la insuficiencia cardíaca. Papel del médico de atención primaria.

Despite traditional treatments, morbidity and mortality of patients with heart failure (HF) and reduced left ventricular ejection fraction remains unacceptably high. Traditionally, guidelines recommended a step by step approach in the management of this population. However, this approach could delay the prescription of some drugs with proven efficacy on morbidity and prognosis. As current HF guidelines recommend, an initial comprehensive approach with the aim of targeting all neurohormonal systems that are implied in the etiopathogenesis of HF seems necessary. The DAPA-HF trial demonstrated that dapagliflozin markedly reduces the risk of HF hospitalization, and also improves prognosis. Consequently, dapagliflozin should be considered as a first-line therapy in the management of these patients. On the other hand, primary care physicians are essential for the prevention and treatment of patients with HF and reduced left ventricular ejection fraction. As a result, it is mandatory that they know when and how dapagliflozin should be used. In this review, a practical approach for an appropriate use of this drug is provided.

[Impact of dapagliflozin on cardiovascular risk factors. Beyond glycemic control]. / Impacto de dapagliflozina en los factores de riesgo cardiovascular. Más allá del control de la glucemia.

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a new class of oral hypoglycemic agents that increase urinary glucose excretion independently of insulin secretion, although an apparently simple mechanism, but with multiple metabolic effects. Dapagliflozin was the first SGLT2 inhibitor marketed in Europe in 2012 for the treatment of patients with type 2 diabetes, and consequently, with the greatest clinical experience. The results of different clinical trials and real-life studies have demonstrated its effectiveness in glycemic control, as they reduce glycosylated hemoglobin, while achieving a decrease in body weight and blood pressure, among others, providing a comprehensive metabolic protection.

SGLT-2 inhibitors: A step forward in the treatment of heart failure with reduced ejection fraction.

Heart failure (HF) is a major health problem with a significant impact on morbidity, mortality, quality of life and healthcare costs. Despite the positive impact of disease-modifying therapies developed over the last four decades, HF mortality and hospitalization remain high. We aim at reviewing the evidence supporting the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors, as a novel strategy for HF with reduced ejection fraction (HFrEF) treatment. The consistent observation of a reduction in HF hospitalizations in type-2 diabetes cardiovascular safety trials EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS raised the hypothesis that SGLT-2 inhibitors could have an impact in HF treatment. This hypothesis was first confirmed in 2019 with the DAPA-HF publication showing that dapagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations and cardiovascular mortality. This was reinforced by the EMPEROR-Reduced publication in 2020 showing that empagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations. Both studies established SGLT-2 inhibitors as a fourth pillar of HFrEF prognosis-modifying therapy, in addition to the gold standard triple neurohormonal modulation/blockade.

Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus. / Efecto de dapagliflozina sobre la rigidez arterial en pacientes con diabetes mellitus tipo 2.

INTRODUCTION: Oral antidiabetic inhibitors of the sodium-glucose cotransporter (SGLT2i) reduce cardiovascular morbidity and mortality in DM2. The increase in arterial stiffness can participate in this morbidity and mortality. The aim of this study was to analyse the effect of the administration of dapagliflozin on arterial stiffness. PATIENTS AND METHODS: Prospective observational study that included 32 patients with DM2. Before starting dapagliflozin, and at 6 and 12 months, biochemical parameters in blood and urine were analysed. Before starting dapagliflozin and at 12 months the velocity of the carotid-femoral pulse (VPc-f) was determined by tonometry. Changes in the variables and their interrelation was analysed by repeated data ANOVA, Wilcoxon's test and multiple regression. RESULTS: A significant decrease in the VPc-f was observed. There was no association between decreased VPc-f and changes in blood glucose, uric acid, blood pressure or weight. CONCLUSIONS: Dapagliflozin, in subjects with DM2, produces a medium to long-term decrease in arterial stiffness.

Lo mejor del Congreso 2019 de la Sociedad Europea de Cardiología / The best of the 2019 European Society of Cardiology Congress / O melhor do Congresso da Sociedade Europeia de Cardiologia 2019

Resumen: El Congreso Europeo de Cardiología constituye uno de los eventos más relevantes de la comunidad cardiológica mundial. Fue realizado entre el 31 de agosto y el 4 de setiembre en el corazón de París, siendo el tema central la salud cardiovascular global. Como es habitual, contó con la presencia de más de 30.000 profesionales y destacados invitados. Se presentaron actualizaciones de varias guías de práctica clínica e importantes trabajos científicos que sin duda impactarán en el tratamiento de los pacientes con patología cardiovascular. A continuación realizaremos un breve resumen de algunos de los trabajos presentados: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Summary: The European Congress of Cardiology is one of the most relevant events of the world cardiology community. It was held from August 31 to September 4 in the heart of Paris, France, the central theme being global cardiovascular health. As usual, it was attended by more than 30,000 professionals and prominent guests. Updates of several clinical practice guides and important scientific papers were presented. These undoubtedly will impact in the treatment of patients with cardiovascular pathology. Below we present a brief summary of some of the trials presented: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Sumário: O Congresso Europeu de Cardiologia é um dos eventos mais relevantes da comunidade mundial de cardiologia. Foi realizada de 31 de agosto ao 4 de setembro no coração de Paris, na França, o tema central foi a saúde cardiovascular global. Como sempre, participaram mais de 30.000 profissionais e convidados de destaque. Atualizações de vários guias de prática clínica e importantes artigos científicos foram apresentados que, sem dúvida, impactarão o tratamento de pacientes com patologia cardiovascular. Abaixo, faremos um breve resumo de alguns trials apresentados: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Cetoacidosis diabética euglucémica secundaria al uso de Dapagliflozina / Euglycemic diabetic ketoacidosis secondary to the use of Dapagliflozin

Los inhibidores del cotransportador sodio-glucosa tipo 2 son un grupo de fármacos que se utilizan en tratamiento de la diabetes tipo 2. Un efecto adverso que pueden producir es la cetoacidosis diabética euglucémica, una entidad clínica que se debe conocer para realizar el adecuado diagnóstico y tratamiento, suspendiendo la administración de dichos fármacos.

Inhibitors of sodium-glucose cotransporter type 2 are a group of drugs used in treatment of type 2 diabetes. Euglycemic diabetic ketoacidosis is an adverse effect that may occur and a clinical entity that should be known for proper diagnosis and treatment, suspending the administration of this medication.

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)

Clinical profile of patients with type 2 diabetes mellitus treated with sodium- glucose cotransporter-2 inhibitors and experience in real-world clinical practice in Spain. / Perfil clínico de los pacientes con diabetes mellitus tipo 2 tratados con inhibidores del cotransportador sodio-glucosa tipo 2 y experiencia clínica real en España.

The main aim of the treatment of type 2 diabetes is overall control of cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not achieve glycaemic targets, and a much higher percentage do not achieve weight and blood pressure targets, despite the therapeutic arsenal that has appeared in the last decade for the treatment of this disease. In addition, antidiabetic secretatogues and insulin are associated with weight gain and an increased risk of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic step as the other options after initiation of metformin therapy. The present study reviews the most appropriate patient profile for SGLT2i therapy, based on their safety and efficacy demonstrated in controlled clinical trials. The article discusses which patients are at risk of experiencing the possible secondary effects due to the mechanism of action of this new therapeutic class, in whom SGLT2i should be used with caution. These considerations on the profile of patients suitable for SGLT2i therapy are contrasted with the results obtained in daily clinical practice, both in retrospective studies from other countries and from real-world experiences in Spain. This article presents a selection of studies performed in distinct centres with a minimum follow-up of 6 months and compares their results with those from clinical trials. SGLT2i are used in clinical practice in any therapeutic step and the efficacy results are very similar to those reported by controlled clinical trials, with a slightly higher proportion of genitourinary infections and a low dropout rate. Half the reported patients are diabetics receiving insulin therapy plus a gliflozin, showing the wide uptake of this therapeutic strategy by clinicians. SGLT2i are especially attractive due to their additional effectiveness in weight and blood pressure control and the possibility of using them in association with other antidiabetic agents or in monotherapy in patients at any stage of type 2 diabetes.

Positioning of sodium-glucose cotransporter-2 inhibitors in national and international guidelines. / Posicionamiento en guías nacionales e internacionales de los inhibidores del cotransportador sodio-glucosa tipo 2.

Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) selectively and reversibly inhibit sodium-glucose cotransporter-2 (SGLT2), promoting renal glucose excretion and reducing plasma glycaemia. By increasing renal glucose excretion, these drugs favour a negative energy balance, leading to weight loss. Their glucoselowering effect is independent of insulin. Although these drugs have only recently been developed, they have been included in all the main national and international guidelines since 2014. The present review summarises the most important recommendations on the use of SGLT2 in patients with DM2 contained in the most recently published guidelines and consensus statements.

[Dapagliflozin: Beyond glycemic control in the treatment of type 2 diabetes mellitus]. / Dapagliflozina: Más allá del control glucémico en el tratamiento de la diabetes mellitus tipo 2.

Patients with type 2 diabetes mellitus (T2DM) have a high or very high cardiovascular risk. The clinical practice guidelines focus on the need to achieve optimal glycemic control, and strategies for a multifactorial therapeutic approach have shown significant cardiovascular benefits in these patients. Inhibitors of sodium-glucose co-transporter 2 (SGLT-2) are a new class of orally administered drugs in the treatment of T2DM, which act by inhibiting reabsorption of glucose in the renal proximal tubule with consequent glycosuric effect and lowering of blood glucose. Dapagliflozin, SGLT-2 inhibitor marketed in Europe and Australia, has been shown to achieve glycosylated hemoglobin reductions similar to other oral agents, as well as beneficial effects on major comorbidities associated with T2DM. Therefore, it is considered of interest to review the clinical efficacy of this new oral hypoglycemic on glycemic control, risk of hypoglycemia, and its impact on body weight, blood pressure, lipid profile and renal function.

[Cost-effectiveness analysis of dapagliflozin compared to DPP4 inhibitors and other oral antidiabetic drugs in the treatment of type-2 diabetes mellitus in Spain]. / Análisis de coste-efectividad de dapagliflozina en comparación con los inhibidores de la DPP4 y otros antidiabéticos orales en el tratamiento de la diabetes mellitus tipo 2 en España.

OBJECTIVE: To assess the efficiency of the combined therapy with metformin and dapagliflozin, a new oral anti-diabetic drug with an insulin-independent mechanism of action, in the treatment of type-2 diabetes mellitus (T2DM) compared to DPP4 inhibitors, sulphonylureas and thiazolidindiones, also combined with metformin. DESIGN: Cost-effectiveness analysis using a discrete event simulation model based on the results of the available clinical trials and considering patient's entire life as time horizon. SETTING: National Health System perspective. PARTICIPANTS: The model simulated the natural history of 30,000 patients with T2DM for each of the options compared. MAIN MEASUREMENTS: Quality-adjusted life-years (QALY) and economic consequences of managing the disease and its complications. The analysis considered direct costs updated to 2013. A discount rate of 3% was applied to costs and health outcomes. RESULTS: In the main analysis comparing dapagliflozin with DPP4 inhibitors, dapagliflozin resulted in a treatment option that would provide a slightly higher effectiveness (0.019 QALY) and lower overall associated costs (-€42). In the additional analyses, dapagliflozin was a cost-effective option compared with sulphonylureas and thiazolidinediones resulting in a cost per QALY gained of €3,560 and €2,007, respectively. The univariate and probabilistic sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: The results of the analyses performed suggested that dapagliflozin, in combination with metformin, would be a cost-effective alternative in the Spanish context for the treatment of T2DM.

Comparação entre dapagliflozina versus sitagliptina como terceira droga em pacientes com diabetes mellitus tipo 2 descompensada em uso metformina e sulfoniluréias / Comparison between dapagliflozin versus sitagliptin as third drug in patients with type 2 diabetes mellitus in uncompensated use metformin and sulfonylurea

Introdução: Diabetes Mellitus, doença crônica, com prevalência crescente. Diabetes mellitus tipo 2 (DM2), é o mais comum e tem obesidade como principal fator de risco. O controle glicêmico é difícil ser alcançado ou mantido com monoterapia ou terapia dupla, sendo necessária adição de terceira droga. O rim foi o foco para criara uma nova droga, denominada Dapagliflozina, devido realizar homeostase da glicose. Está é via oral, um inibidor de SGLT2, visto que bloqueia a reabsorção renal de glicose, excreta 70g de glicose ao dia, (correspondente a 280 kcal/dia). Adição a hipoglicemiantes orais mostrou redução hemoglobina glicada (HbA1C), perda de peso, circunferência abdominal e massa gorda abdominal.Objetivos: Comparar eficácia e tolerabilidade entre Dapagliflozina e Sitaglipitina, como terceira droga para tratamento de DM2 descompensado já em uso da combinação de Metformina e Sulfonilureias. Métodos: Seleção de pacientes DM2 descompensados com Metformina e Sulfonilureia. Eles receberam Dapagliflozina 10mg/dia por 12 semanas. Avaliado hemoglobina glicada, glicemia de jejum, peso e circunferência abdominal e a tolerabilidade. Resultados foram comparados com trabalho da Guastapaglia, aonde Sitagliptina 100 mg/dia foi adicionada. Resultados: Média da HbA1c basal foi 8,5%, após 12 semanas houve redução da HbA1C -0,81% e glicemia de jejum de -10 mg/dL. Peso e circunferência abdominal diminuíram (-3kg e -3cm). Relação LDL/HDL não ocorreu alteração, assim como pressão arterial, função renal e hepática. Efeitos colaterais foram vulvovaginite (23,5%) e cistite (11,7%).Conclusão: Ao comparar Dapagliflozina com Sitagliptina, a redução da HbA1C foi semelhante, porem a Dapagliflozina promoveu perda de peso, mas apresentou efeitos colaterais mais graves. Ambas são efetivas para serem adicionadas a DM2 descompensados com Metformina e Sulfonilureia (AU)

Avaliação da eficácia e tolerabilidade da dapagliflozina quando adicionada à terapia combinada de metformina e sulfoniluréia no tratamento do diabetes mellitus tipo 2 / Efficacy and tolerability of dapagliflozin when added to combination therapy of metformin and sulfonylurea in the treatment of type 2 diabetes mellitus

Introdução: O Diabetes Mellitus é uma condição crescente em todo o mundo. Em pacientes DM2, um ótimo controle glicêmico é dificilmente alcançado ou mantido a longo-prazo, independente do tratamento. A fisiopatologia complexa e a natureza progressiva do DM2, muitas vezes, tornam ineficaz o tratamento em monoterapia com os agentes anti-diabéticos disponíveis atualmente. Afim de, evitar a progressão da doença, é fundamental uma intervenção terapêutica precoce para preservar a função das células β e aumentar a sensibilidade à insulina. Objetivos: Revisão bibliográfica e apresentação dos resultados iniciais da eficácia e a tolerabilidade da adição da dapagliflozina ao tratamento de pacientes com DM2 em uso de metformina e sulfoniluréia. Métodos: Estudo de coorte prospectivo com a randomização de pacientes com DM2, em uso regular de metformina associada à sulfoniluréia por no mínimo 12 semanas e controle glicêmico inadequado. Os pacientes que preencherem os critérios receberam dapagliflozina na dose de 10mg/dia por 12 semanas, em dose diária única. Níveis variáveis foram avaliados no início e após a introdução do tratamento. Resultados: 6 pacientes completaram tratamento. Os níveis de glicemia de jejum apresentaram redução de 16,12% em relação aos valores iniciais. Redução de peso ocorreu na maioria dos pacientes e o efeito-colateral mais temido da medicação, a infecção de trato genito-urinário, não teve repercussão importante em nossa casuística. Conclusão: Não existe um único antidiabético que possa corrigir todos os distúrbios metabólicos. Portanto, uma terapia eficaz exige múltiplas drogas em combinação. Inibidores do SGLT2 podem ser utilizados como monoterapia e em combinação com outros anti-diabéticos.(AU)

Avaliação da eficácia e tolerabilidade da dapagliflozina quando adicionada à terapia combinada de metformina e sulfoniluréia no tratamento de diabetes mellitus tipo2 / Evaluation of the efficacy and tolerability of dapagliflozin when added to metformin and sulfonylurea combination therapy in the treatment of type 2 diabetes mellitus

O Diabetes Mellitus é uma condição crescente em todo o mundo. Em pacientes DM2, um ótimo controle glicêmico é dificilmente alcançado ou mantido a longo-prazo, independente do tratamento. Apenas 25% dos pacientes estão bem controlados após 9 anos de doença. A fisiopatologia complexa e a natureza progressiva do DM2, muitas vezes, tornam ineficaz o tratamento em monoterapia com os agentes anti-diabéticos disponíveis atualmente. Afim de, evitar a progressão da doença, é fundamental uma intervenção terapêutica precoce para preservar a função das células ß e aumentar a sensibilidade à insulina. A associação medicamentosa mais frequente utilizada no Brasil é metformina com sulfoniuréia. Porém, assim como em monoterapias, um controle glicêmico ideal pode não ser atingido. Em janeiro de 2014, foi liberado pela Food and Drug Administration, o uso e comercialização de um novo medicamento para tratamento do DM2, a dapagliflozina. Um bloqueador do SGLT2, proteína responsável pela reabsorção da glicose no rim, levando a glicosúria com consequente melhora do controle glicêmico. Sua adição a outros hipoglicemiantes orais mostrou redução significativa dos níveis séricos de HbA1c, com resultados promissores em relação a eficácia e segurança, ou seja, uma nova abordagem terapêutica com potencial para o tratamento do DM2. Objetivos: Revisão bibliográfica e apresentação dos resultados iniciais da eficácia e a tolerabilidade da adição da dapagliflozina ao tratamento de pacientes com DM2 em uso de metformina e sulfoniluréia. Métodos: Estudo de coorte prospectivo com a randomização de pacientes com DM2, em uso regular de metformina associada à sulfoniluréia por no mínimo 12 semanas e controle glicêmico inadequado. Os pacientes que preencherem os critérios receberam dapagliflozina na dose de 10mg/dia por 12 semanas, em dose diária única. Variáveis como níveis séricos de HbA1c, glicemia de jejum, insulina, perfil lipídico, creatinina, urina 1, urocultura, índice de massa corpórea (definido com peso/altura²), circunferência abdominal e pressão arterial foram avaliados no início e após a introdução do tratamento. Efeitos colaterais previstos em bula e demais reações adversas durante o uso da medicação foram questionados, tratados com suspensão imediata do fármaco e exclusão do estudo. Resultados: 6 pacientes completaram tratamento. Os níveis de glicemia de jejum apresentaram redução de16,12% em relação aos valores iniciais. HbA1c foi dosada inicialmente nos pacientes, porém devido dificuldades técnicas o exame não foi realizado no controle. Redução de peso ocorreu na maioria dos pacientes, porém em porcentagem menor do que a descrita pelos trabalhos realizados em monoterapia. O efeito-colateral mais temido da medicação, a infecção de trato genito-urinário, não teve repercussão importante em nossa casuística. Conclusão: Não existe um único antidiabético que possa corrigir todos os distúrbios metabólicos. Portanto, uma terapia eficaz exige múltiplas drogas em combinação. Inibidores do SGLT2 podem ser utilizados como monoterapia e em combinação com outros anti-diabéticos. Apesar de se tratar de uma medicação em fase III e os resultados obtidos até o momento revelarem um importante impacto no tratamento de DM2, novos estudos são necessários para avaliar os resultados de segurança, os efeitos a longo prazo e as complicações diabéticas.