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1.
Int. j. cardiovasc. sci. (Impr.) ; 35(1): 95-106, Jan.-Feb. 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1356307

RESUMO

Abstract Background: Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular impairment, increasing the rates of atherosclerotic and non-atherosclerotic events. Additionally, adverse kidney events are directly linked with T2DM and cardiovascular diseases. In this context, the sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated both cardioprotective and renoprotective effects in patients with or without T2DM. Therefore, the present meta-analysis aims to evaluate cardiovascular outcomes involving SGLT2i as monotherapy or other add-on antidiabetic agents (ADA) in patients with or without T2DM. Objetive: The present meta-analysis aims to evaluate cardiovascular outcomes involving SGLT2i as monotherapy or add-on other ADA in patients with or without T2DM. Methods: The entrance criteria to SGLT2i studies were: describing any data regarding cardiovascular effects; enrolling more than 1,000 participants; being approved by either the FDA or the EU, and having available access to the supplementary data. The trial had to exhibit at least one of the following results: major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure, cardiovascular death, hospitalization for heart failure, renal or cardiovascular adverse events, or non-cardiovascular death. The significance level of 0.05 was adopted in the statistical analysis. Results: Nine trials with a total of 76,285 participants were included in the meta-analysis. SGLT2i reduced MACE (RR 0.75, 95% CI [0.55-1.01]), cardiovascular death or hospitalization for heart failure (RR 0.72, 95% CI [0.55-0.93]), cardiovascular death (RR 0.66, 95% CI [0.48-0.91]), hospitalization for heart failure (RR 0.58, 95% CI [0.46-0.73]), renal or cardiovascular adverse events (RR 0.55, 95% CI [0.39-0.78]), and non-cardiovascular death (RR 0.88, 95% CI [0.60-1.00]). Conclusions: Conjunction overall data suggests that these drugs can minimize the risk of cardiovascular events, thus decreasing mortality in patients, regardless of the presence of T2DM.


Assuntos
Humanos , Cardiotônicos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Reprodutibilidade dos Testes , Avaliação de Resultados em Cuidados de Saúde , Transportador 2 de Glucose-Sódio , Hospitalização , Nefropatias/tratamento farmacológico
2.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 66(supl.1): s17-s24, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1057108

RESUMO

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.


Assuntos
Humanos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Transportador 2 de Glucose-Sódio/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Hipoglicemiantes/farmacologia , Nefropatias/prevenção & controle , Compostos Benzidrílicos/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/prevenção & controle , Transportador 2 de Glucose-Sódio/uso terapêutico , Canagliflozina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Taxa de Filtração Glomerular , Glucose/metabolismo , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Rim/efeitos dos fármacos , Rim/fisiopatologia , Rim/metabolismo , Nefropatias/etiologia , Nefropatias/metabolismo
3.
Rev. chil. endocrinol. diabetes ; 12(2): 124-132, abr. 2019. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-995453

RESUMO

La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.


Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.


Assuntos
Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Quimioterapia Adjuvante , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Transportador 2 de Glucose-Sódio/antagonistas & inibidores , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Metformina/uso terapêutico
4.
Int. braz. j. urol ; 45(1): 169-178, Jan.-Feb. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-989961

RESUMO

ABSTRACT Purpose: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). Materials and Methods: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. Results: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. Conclusions: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Proteínas de Transporte de Sódio-Glucose/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Neoplasias Renais/metabolismo , Prognóstico , Imuno-Histoquímica , Análise de Sobrevida , Pessoa de Meia-Idade , Estadiamento de Neoplasias
5.
Arch. endocrinol. metab. (Online) ; 62(4): 424-430, July-Aug. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-950077

RESUMO

ABSTRACT Objective: This analysis compared the efficacy and safety of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin, both added on to metformin. Materials and methods: This was a post-hoc analysis from a double-blind, randomized, 24-week clinical trial (NCT01606007) of patients with type 2 diabetes (T2D) inadequately controlled with metformin. We compared the dapagliflozin 10 mg (n = 179) and saxagliptin 5 mg (n = 176) treatment arms. Results: Dapagliflozin showed significantly greater mean reductions versus saxagliptin in HbA1c (difference versus saxagliptin [95% CI]: −0.32% [-0.54, −0.10]; p < 0.005), fasting plasma glucose (-0.98 [-1.42, −0.54] mmol/L; p < 0.0001), body weight (-2.39 [-3.08, −1.71] kg; p < 0.0001) and systolic blood pressure (SBP) (-3.89 [-6.15, −1.63] mmHg; p < 0.001). More dapagliflozintreated than saxagliptin-treated patients achieved the composite endpoint of HbA1c reduction ≥ 0.5%, weight loss ≥ 2 kg, SBP reduction ≥ 2 mmHg and no major/minor hypoglycemia (24% versus 7%). No major events of hypoglycemia were reported. More patients on dapagliflozin (6%) versus saxagliptin (0.6%) experienced genital infections. Conclusion: Dapagliflozin demonstrated greater glycemic efficacy than saxagliptin with additional benefits on weight and SBP, and the safety profile was consistent with previous studies.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Compostos Benzidrílicos/uso terapêutico , Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Adamantano/efeitos adversos , Adamantano/uso terapêutico , Método Duplo-Cego , Diabetes Mellitus Tipo 2/sangue , Dipeptídeos/efeitos adversos , Transportador 2 de Glucose-Sódio/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico
6.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 63(7): 636-641, July 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-896368

RESUMO

Summary Introduction: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. Objective: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile. Method: A literature search on Pubmed database was performed using the following keywords: "SGLT-2 inhibitors," "dapagliflozin," "empagliflozin," "canagliflozin." Results: SGLT-2 inhibitors are a class of oral antidiabetic drugs directed to the kidney. Their mechanism of action is to reduce blood glucose by inducing glycosuria. Extra-glycemic benefits have been described, such as weight loss, decline in blood pressure and levels of triglycerides and uric acid, and they can slow the progression of kidney disease. Genitourinary infections are the main side effects. There is a low risk of hypotension and hypoglycemia. Diabetic ketoacidosis is a serious adverse effect, although rare. Empagliflozin has already had its cardiovascular benefit demonstrated and studies with other drugs are currently being performed. Conclusion: SGLT-2 inhibitors are a new treatment option for type 2 diabetes mellitus, acting independently of insulin. They have potential benefits other than the reduction of blood glucose, but also carry a risk for adverse effects.


Resumo Introdução: O diabetes mellitus é uma das doenças crônicas mais frequentes no mundo, com altas taxas de morbimortalidade, resultando em um grande impacto negativo socioeconômico. Apesar de existirem diversas classes de antidiabéticos orais, a maioria dos pacientes acometidos está fora da meta terapêutica. Objetivo: Revisar o uso dos inibidores da SGLT-2 no tratamento do diabetes mellitus tipo 2, com enfoque nos efeitos favoráveis, desfavoráveis e no perfil cardiovascular. Método: Foi realizada uma pesquisa bibliográfica transversal com artigos científicos obtidos da base de dados Pubmed, utilizando os descritores: "SGLT-2 inhibitors", "dapagliflozin", "empagliflozin", "canagliflozin". Resultados: Os inibidores da SGLT-2 são uma classe de antidiabéticos orais com atuação no rim. O mecanismo de ação é reduzir a glicemia induzindo glicosúria. Benefícios extraglicêmicos já foram descritos, como redução de peso, pressão arterial, triglicerídeos e ácido úrico, além de retardar a progressão da doença renal. O principal efeito colateral é a infecção geniturinária, com baixo risco de hipotensão e hipoglicemia. Cetoacidose diabética é um efeito adverso grave, mas infrequente. A empagliflozina já teve seu benefício cardiovascular demonstrado, e estudos com outras drogas estão em andamento. Conclusão: Os inibidores da SGLT-2 são uma nova opção de tratamento do diabetes mellitus tipo 2, que atua de forma insulino-independente e com potenciais benefícios adicionais, além da redução da glicemia, mas também com risco de efeitos adversos.


Assuntos
Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose , Hipoglicemiantes/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Glicemia/efeitos dos fármacos , Transportador 2 de Glucose-Sódio , Canagliflozina/uso terapêutico , Glucosídeos/uso terapêutico , Hipoglicemiantes/efeitos adversos , Rim/efeitos dos fármacos
7.
Rev. cuba. endocrinol ; 27(2): 0-0, mayo.-ago. 2016.
Artigo em Espanhol | LILACS | ID: lil-780735

RESUMO

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)


Assuntos
Humanos , Terapia Combinada/métodos , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/uso terapêutico , Acervo de Biblioteca/estatística & dados numéricos , Transportador 2 de Glucose-Sódio/uso terapêutico
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