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1.
Rev. bras. med. fam. comunidade ; 17(44): 2428, 20220304. ilus, tab
Article in Portuguese | LILACS, ColecionaSUS | ID: biblio-1380389

ABSTRACT

Introdução: Introdução: Diabetes mellitus tipo 2 é um importante e crescente problema de saúde para todos os países. Objetivo: Este trabalho visa avaliar a qualidade da evidência disponível sobre os fármacos inibidores de sódio-glicose 2 e agonistas de glucagon 1 em pessoas com diabetes mellitus e doença cardiovascular aterosclerótica Métodos: Realizou-se revisão integrativa utilizando as bases de dados MEDLINE via PubMed, Embase via Cochrane Library, Cochrane Library, LILACS via BVS. A pergunta de pesquisa foi estruturada da seguinte forma: população ­ pessoas com diabetes mellitus tipo 2 e doença cardiovascular estabelecida; intervenção ­ tratamento usual exceto insulina + inibidores de sódio-glicose 2 ou tratamento usual exceto insulina + agonistas de glucagon 1; controle - tratamento usual exceto insulina + placebo; desfecho ­ mortalidade geral, mortalidade por causas cardiovasculares, morbidade, efeitos adversos. Resultados: Selecionaram-se dois estudos sobre empagliflozina. Esse medicamento associado ao tratamento usual foi superior ao placebo associado ao tratamento usual no desfecho primário (HR 0,86; IC95% 0,74­0,99; p=0,04), na redução de hospitalização por insuficiência cardíaca (HR 0,65; IC95% 0,50­0,85; p=0,002), da mortalidade cardiovascular (HR 0,62; IC95% 0,49­0,77) e da mortalidade geral (HR 0,68; IC95% 0,57­0,82; p<0,001). No subgrupo de pessoas com diabetes que não usavam insulina, houve benefício com empagliflozina em relação ao desfecho primário (HR 0,79; IC95% 0,64­0,97; DR 2,5; NNT 40) e a mortes de causa cardiovascular (HR 0,61; IC95% 0,44­0,85; DR 2; NNT 49). Houve heterogeneidade entre os subgrupos com benefício de empagliflozina no desfecho primário apenas para aqueles com idade ³65 anos (p=0,01) e hemoglobina glicada <8,5 (p=0,01). Em relação às mortes por causas cardiovasculares, houve diferença (p=0,05) com o uso de empagliflozina reduzindo o risco somente no subgrupo com índice de massa corporal <30. Não houve diferença significativa em relação ao placebo para acidente vascular encefálico fatal e não fatal, tampouco no desfecho composto de acidente vascular encefálico debilitante não fatal e acidente vascular encefálico fatal (HR 0,81; IC95% 0,43­1,50; p=0,50). Houve mais pessoas acometidas por acidente vascular encefálico no grupo intervenção em que a hemoglobina glicada inicial era ≥8,5%, favorecendo o placebo (p=0,01). Conclusões: Os dados encontrados favorecem o benefício de utilizar esse medicamento no Sistema Único de Saúde em pessoas com doenças cardiovasculares. Entretanto, houve heterogeneidade entre grupos populacionais, o que pode ajudar a delinear estratégias de uso para esses medicamentos. São necessários mais estudos para avaliar qual seria o motivo de não haver benefício em desfechos cerebrovasculares isoladamente.


Introduction: Introduction: Type 2 diabetes mellitus is an important and growing health problem worldwide. Objective: This study aims to evaluate the quality of the evidence available on sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists in people with diabetes mellitus and atherosclerotic cardiovascular disease. Methods: This integrative review was performed using the following databases: MEDLINE via PubMed, Embase via Cochrane Library, Cochrane Library, LILACS via VHL. The research question was structured as follows: population ­ people with type 2 diabetes mellitus and established cardiovascular disease; intervention ­ usual treatment, except insulin + sodium-glucose cotransporter 2 inhibitors or usual treatment, except insulin + and glucagon-like peptide 1 agonists; control ­ usual treatment, except insulin + placebo; outcome ­ overall mortality, mortality from cardiovascular causes, morbidity, adverse effects. Results: Two studies on empagliflozin were selected. This drug associated with the usual treatment was superior to placebo associated with the usual treatment in the primary outcome (hazard ratio ­ HR 0.86; 95% confidence interval ­ 95%CI 0.74­0.99; p=0.04), in reducing heart failure hospitalization (HR 0.65; 95%CI 0.50­0.85; p=0.002), in cardiovascular mortality (HR 0.62; 95%CI 0.49­0.77), and in overall mortality (HR 0.68; 95%CI 0.57­0.82; p<0.001). The subgroup of people with diabetes who were not on insulin benefited from using empagliflozin concerning the primary outcome (HR 0.79; 95%CI 0.64­0.97; risk difference ­ RD 2.5; number needed to treat ­ NNT 40) and cardiovascular mortality (HR 0.61; 95%CI 0.44­0.85; RD 2; NNT 49). The analysis of the subgroups showed heterogeneity. Participants aged 65 years or older (p=0.01) and those with glycated hemoglobin lower than 8.5 benefited from empagliflozin in the primary outcome. A difference (p=0.05) related to cardiovascular mortality was found, with the use of empagliflozin reducing the risk only in the subgroup with body mass index <30. No significant difference was identified with respect to placebo for fatal and nonfatal stroke nor for the composite outcome of nonfatal disabling stroke and fatal stroke (HR 0.81; 95%CI 0.43­1.50; p=0.50). More people had strokes in the intervention group in which the initial glycated hemoglobin was ≥8.5%, favoring placebo (p=0.01). Conclusions: The data found suggest the benefit of the Brazilian public health system using this drug in people with cardiovascular diseases. However, the population groups were heterogeneous, which may help outline strategies for using these medications. Further studies are necessary to assess why isolated cerebrovascular outcomes showed no benefit.


Introducción: Diabetes mellitus tipo 2 es un importante y creciente problema de salud para todos los países. Objetivo: Este trabajo busca evaluar la calidad de la evidencia disponible sobre los fármacos Inhibidores del Cotransportador de Sodio-Glucosa 2 y agonistas de Péptido 1 similar al glucagón en personas con diabetes mellitus y enfermedad cardiovascular aterosclerótica. Métodos: Se realizó revisión integrativa utilizando las bases de datos MEDLINE vía PubMed, Embase vía Cochrane Library, Cochrane Library, LILACS vía BVS. La pregunta de investigación fue estructurada de la siguiente manera: población ­ personas con diabetes mellitus tipo 2 y enfermedad cardiovascular establecida; intervención ­ tratamiento usual excepto insulina + inhibidores de sodium-glucose cotransporter-2 o tratamiento usual excepto insulina + agonistas de Péptido 1 similar al glucagón; control ­ tratamiento habitual excepto insulina + placebo; desenlace ­ mortalidad general, mortalidad por causas cardiovasculares, morbilidad, efectos adversos. Resultados: Se seleccionaron dos estudios sobre empagliflozina. Este medicamento asociado al tratamiento habitual fue superior al placebo asociado al tratamiento usual en el resultado primario (HR 0.86; IC95% 0.74­0.99; p=0,04), en la reducción de hospitalización por insuficiencia cardíaca (HR 0.65; IC95% 0.50­0.85; p=0.002), de la mortalidad cardiovascular (HR 0,62; IC95% 0,49­0,77) y de la mortalidad general (HR 0,68; IC95% 0,57­0,82; p=0,001). En el subgrupo de personas con diabetes que no usaban insulina, hubo beneficio con empagliflozina con relación al desenlace primario (HR 0.79; IC95% 0.64­0.97; DR 2.5; NNT 40) y a muertes de causa cardiovascular (HR 0.61; IC95% 0.44­0.85; DR 2; NNT 49). No hubo diferencia significativa con relación al placebo para accidentes cerebrovasculares fatal y no fatal, tampoco en el resultado compuesto de accidente cerebrovascular debilitante no fatal y fatal (HR 0.81; IC95% 0.43­1.50; p=0.50). Hubo más personas acometidas por accidente cerebrovascular en el grupo intervención en que la hemoglobina glicada inicial era un 8,5%, favoreciendo el placebo (p=0.01). Conclusión: Los datos encontrados favorecen el beneficio de utilizar ese medicamento en el Sistema Único de Salud en personas con enfermedad cardiovascular. Entretanto ha habido heterogeneidad entre los grupos de población, lo que puede ayudar a delinear qué estrategias de uso para estos medicamentos. Son necesarios más estudios para evaluar cuál sería el motivo de no haber beneficio en resultados cerebrovasculares aisladamente.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide 1 , Sodium-Glucose Transporter 2 Inhibitors
2.
Int. j. cardiovasc. sci. (Impr.) ; 35(1): 95-106, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1356307

ABSTRACT

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.


Subject(s)
Humans , Cardiotonic Agents , Cardiovascular Diseases/mortality , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Reproducibility of Results , Outcome Assessment, Health Care , Sodium-Glucose Transporter 2 , Hospitalization , Kidney Diseases/drug therapy
3.
Arch. endocrinol. metab. (Online) ; 66(1): 68-76, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1364297

ABSTRACT

ABSTRACT The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI −0.66 to −0.59) and body weight by 0.60 kg (95% CI −0.64 to −0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.


Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use , Blood , Body Weight , Brazil , Glycated Hemoglobin A/analysis , Randomized Controlled Trials as Topic , Canagliflozin/therapeutic use
4.
Protein & Cell ; (12): 336-359, 2022.
Article in English | WPRIM | ID: wpr-929159

ABSTRACT

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na+/H+ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.


Subject(s)
Animals , Diabetes Mellitus , Diabetes Mellitus, Type 2/drug therapy , Glucose , Humans , Mice , Myocardial Infarction/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Ventricular Remodeling
5.
Rev. bras. hipertens ; 28(4): 283-287, 10 dez. 2021.
Article in Portuguese | LILACS | ID: biblio-1367465

ABSTRACT

A doença cardiovascular (DCV) representa um fardo individual e social em pacientes com diabetes mellitus tipo 2 (DM2). A diabetes é uma doença crônica onerosa do ponto de vista social e econômico. O seu tratamento inclui medidas não farmacológicas, como dieta e exercício físico, bem como a adição de medicamentos em pacientes que não atingem controle glicêmico satisfatório através de medidas comportamentais. Medicamentos da classe inibidores de SGLT2 (iSGLT2), objeto deste manuscrito, têm sido associados com a redução de eventos cardiovasculares e mortalidade, além de redução da pressão arterial e peso, sem conferir aumento de risco de hipoglicemia


Cardiovascular disease (CVD) represents an individual and social burden in patients with type 2 diabetes mellitus (T2DM). Diabetes is a chronic, socially and economically costly disease. Its treatment includes non-pharmacological measures, such as diet and exercise, as well as the addition of medication in patients who do not achieve satisfactory glycemic control through behavioral approach. Drugs as SGLT2 inhibitor (SGLT2i), object of this manuscript, have been associated with a reduction in cardiovascular events and mortality, in addition to a reduction in blood pressure and weight, without increasing the risk of hypoglycemia.


Subject(s)
Diabetes Mellitus/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Hypertension/drug therapy
6.
Rev. urug. cardiol ; 36(2): e401, ago. 2021. ilus, tab
Article in Spanish | LILACS, BNUY, UY-BNMED | ID: biblio-1289997

ABSTRACT

La diabetes mellitus, la insuficiencia cardíaca y la enfermedad renal crónica tienen alta prevalencia en la población. Asimismo, estas patologías están comprendidas en un "círculo vicioso" porque comparten mecanismos fisiopatológicos que predisponen a su coexistencia en un mismo paciente, incrementando significativamente el riesgo de eventos cardiovasculares. Recientemente se han agregado al arsenal terapéutico las gliflozinas, un grupo de fármacos con beneficios en las tres enfermedades mencionadas. Saber cómo se desarrolló la investigación con estos fármacos y sus mecanismos de acción es fundamental para optimizar el tratamiento de los pacientes.


Diabetes mellitus, heart failure, and chronic kidney disease are highly prevalent in the population. Likewise, these pathologies are included in a "vicious circle" because they share pathophysiological mechanisms that predispose to their coexistence in the same patient, significantly increasing the risk of cardiovascular events. Gliflozins, a group of drugs with benefits in the three mentioned pathologies, have recently been added to the therapeutic arsenal. Knowing how research with these drugs and its mechanisms of action is essential to optimize the treatment of patients.


Diabetes mellitus, insuficiência cardíaca e doença renal crônica são altamente prevalentes na população. Estas patologias fazem parte de um "círculo vicioso", compartilhando mecanismos fisiopatológicos que predispõem à coexistência no mesmo paciente, e aumentando significativamente o risco de eventos cardiovasculares. As gliflozinas, são un grupo de drogas com benefícios das três patologias citadas, foram adicionadas recentemente ao arsenal terapêutico. Saber como foram desenvolvidas as pesquisas com esses medicamentos e seus mecanismos de ação é essencial para otimizar o tratamento dos pacientes.


Subject(s)
Humans , Diabetes Mellitus/drug therapy , Renal Insufficiency, Chronic/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Heart Failure/drug therapy , Hypoglycemic Agents/pharmacology , Treatment Outcome
8.
Chinese Medical Journal ; (24): 1317-1323, 2021.
Article in English | WPRIM | ID: wpr-878102

ABSTRACT

BACKGROUND@#Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.@*METHODS@#This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.@*RESULTS@#We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.@*CONCLUSIONS@#The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.


Subject(s)
Benzhydryl Compounds , Canagliflozin , Cardiovascular Diseases , China , Diabetes Mellitus, Type 2/drug therapy , Glucosides , Humans , Male , Sodium-Glucose Transporter 2 Inhibitors , Tertiary Care Centers
9.
Evid. actual. práct. ambul ; 24(4): e002166, 2021.
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: biblio-1359440

ABSTRACT

En este artículo, la autora jerarquiza la relevancia de la eficacia documentada de los agonistas del péptido similar alglucagón-1 y los inhibidores del cotransportador sodio-glucosa tipo 2, que ha conducido a recientes modificaciones en el paradigma del cuidado en los pacientes con diabetes tipo 2. (AU)


In this article, the author highlights the relevance of the documented efficacy of glucagon-like peptide-1 agonists and type 2 sodium-glucose cotransporter inhibitors, which has led to recent changes in the paradigm of care in patients with type 2diabetes. (AU)


Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide 1/therapeutic use , Glucagon-Like Peptide 1/agonists , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use
12.
Rev. cuba. endocrinol ; 31(3): e250, sept.-dic. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156399

ABSTRACT

Introducción: Los medicamentos inhibidores del cotransportador sodio-glucosa actúan inhibiéndose de forma selectiva y reversible a nivel renal. A través de este mecanismo, reducen la reabsorción de glucosa, la cual pasa a excretarse por la orina y de esta forma, contribuyen a normalizar la glucemia. Objetivo: Describir la función de los inhibidores del cotransportador sodio-glucosa tipo 2 en el tratamiento de la diabetes mellitus. Métodos: Se utilizó como buscador de información científica a Google Académico, Google, Pubmed y SciELO. Se evaluaron artículos de revisión, de investigación y páginas Web, que en general, tenían menos de 10 años de publicados, en idioma español, portugués o inglés. Fueron excluidos los artículos que no cumplieron con estos requisitos. Esto permitió el estudio de 98 artículos, de los cuales 75 fueron referenciados. Conclusiones: La administración de los inhibidores del cotransportador sodio-glucosa induce cambios favorables en la hemoglobina glucosilada, el peso corporal y la presión arterial, además de presentar un bajo riesgo de hipoglucemia. Aunque constituyen un grupo farmacológico que puede ser utilizado como monoterapia, con mayor frecuencia son usados como coadyuvantes en el tratamiento de los pacientes con diabetes mellitus, que reciben tratamiento farmacológico con otros medicamentos normo o hipoglucemiantes y que no han alcanzado las metas de control. Se debe estar alerta ante la aparición de posibles efectos secundarios o reacciones adversas, para descontinuar el tratamiento y tomar las medidas correspondientes(AU)


Introduction: Sodium-glucose co-transporter inhibitors´ drugs (SGLT) work by selectively and reversiblely inhibiting at the renal level. Through this mechanism, they reduce glucose reabsorption, which is excreted through urine and thus contribute to normalizing blood glucose. Objective: Describe the role of sodium-glucose co-transporter inhibitors 2 in the treatment of diabetes mellitus. Methods: There were used as search engines for scientific information : Google Scholar, Google, Pubmed and SciELO. The keywords used were: Glyphozines, sodium-glucose co-transporter inhibitors, diabetes mellitus, treatment and weight loss. Review articles, research articles and web pages were assessed, which generally had less than 10 years of publication, and were in Spanish, Portuguese or English language. Items that did not meet these requirements were excluded. This allowed the study of 98 articles, of which 75 were referenced. Conclusions: Administration of sodium-glucose co-transporter inhibitors induces favorable changes in glycosylated haemoglobin, body weight and blood pressure, as well as a low risk of hypoglycaemia. Although they are a pharmacological group that can be used as monotherapy, they are mostly used as adjuvants in the treatment of patients with diabetes mellitus who receive drug treatment with other normo or hypoglycemic medications and who have not met control goals. It is important to be alert to possible side effects or adverse reactions to discontinue treatment and take appropriate action(AU)


Subject(s)
Humans , Diabetes Mellitus/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use , Review Literature as Topic , Search Engine/methods
13.
J. bras. nefrol ; 42(4): 467-477, Oct.-Dec. 2020. graf
Article in English, Portuguese | LILACS | ID: biblio-1154642

ABSTRACT

ABSTRACT Sodium glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) were initially approved to improve glycemic control in the treatment of type 2 diabetes. Clinical trials have also demonstrated beneficial effects with regards to cardiovascular and renal parameters. Beyond improving glycemic control, these therapies promote weight loss and lower blood pressure when used individually, and in an additive manner when used together. Accordingly, taking advantage of complementary mechanisms of action with the combined use of these two classes of agents to further improve cardiorenal outcomes is conceptually appealing, but has yet to be explored in detail in clinical trials. In this review, we discuss proposed mechanisms for renal protection, clinical benefits, and adverse events associated with the individual and combined use of SGLT2 inhibitors and GLP-1RA. The management of type 2 diabetes has significantly changed over the last few years, moving away from solely glycemic control towards the concurrent management of associated comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors and GLP-1RA in patients with type 2 diabetes.


RESUMO Inibidores do cotransporter-2 de glicose sódica (SGLT2) e agonistas do receptor peptídeo-1 do tipo glucagon (GLP-1RA) foram inicialmente aprovados para melhorar o controle glicêmico no tratamento da diabetes tipo 2. Os ensaios clínicos também demonstraram efeitos benéficos em relação aos parâmetros cardiovasculares e renais. Além de melhorar o controle glicêmico, essas terapias promovem perda de peso e redução da pressão arterial quando usadas individualmente, e de forma aditiva quando usadas em conjunto. Consequentemente, tirar proveito de mecanismos de ação complementares com o uso combinado dessas duas classes de agentes para melhorar ainda mais os resultados cardiorrenais é conceitualmente atraente, mas ainda precisa ser explorado em detalhes em ensaios clínicos. Nesta revisão, discutimos os mecanismos propostos para proteção renal, benefícios clínicos e eventos adversos associados ao uso individual e combinado de inibidores de SGLT2 e GLP-1RA. O tratamento do diabetes tipo 2 mudou significativamente nos últimos anos, passando do controle exclusivamente glicêmico para o tratamento simultâneo de comorbidades associadas em uma população de pacientes com risco significativo de doença cardiovascular e progressão da doença renal crônica. É nessa perspectiva que procuramos delinear a justificativa para o uso sequencial e/ou combinado de inibidores de SGLT2 e GLP-1RA em pacientes com diabetes tipo 2.


Subject(s)
Humans , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents/therapeutic use
14.
Rev. Assoc. Med. Bras. (1992) ; 66(9): 1283-1288, Sept. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1136379

ABSTRACT

SUMMARY The pharmacological therapy for type 2 diabetes mellitus has presented important advances in recent years, which has impacted the treatment of patients with established cardiovascular disease or with high cardiovascular risk. In this scenario, two drug classes have emerged and demonstrated clear clinical benefits: SGLT-2 inhibitors and GLP-1 agonists. The present review discusses the pharmacology, adverse effects, and clinical trials that have demonstrated the benefits of these medications in reducing cardiovascular risk.


RESUMO A terapia farmacológica do diabetes mellitus tipo 2 apresentou avanços importantes nos últimos anos, impactando principalmente o tratamento dos pacientes com doença cardiovascular estabelecida ou com alto risco cardiovascular. Nesse cenário, surgiram duas classes de fármacos com claros benefícios clínicos; os inibidores da SGLT-2 e os agonistas do GLP-1. Na presente revisão os autores discutem desde a farmacologia, efeitos adversos e também os estudos clínicos que demonstraram os benefícios dessas medicações na redução de risco cardiovascular.


Subject(s)
Humans , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Risk Factors , Sodium-Glucose Transporter 2 Inhibitors
15.
Actual. osteol ; 16(2): [95]-[103], mayo.-ago. 2020. ilus, graf, tab
Article in English | LILACS | ID: biblio-1129692

ABSTRACT

Introduction. Diabetes is a chronic disease associated with important comorbidities. Type 2 diabetes (T2DM) is associated with a three times increased risk of hip fracture but reports describing potential associations with vertebral fractures (VF) are contradictory. Our objective was to evaluate the factors involved in the prevalent VF in women with and without T2DM. Materials and methods. A cross-sectional design was used and the relationship between morphometric VF and T2DM in adult women was evaluated. The cases were adult women with morphometric VF and the controls were adult women without VF. Thoracic and spinal radiographs in lateral and antero-posterior projections were obtained. Bone mineral density (BMD) values of the lumbar spine (L-BMD) were measured by DXA. Results. A greater number of women with T2DM were found in the VF group (61% vs 31.5%). Non-T2DM women with VF were significantly older and with lower L-BMD than non-T2DM without VF. We observed a negative correlation between age and L-BMD (r=-0.463) in non-T2DM women, but not in the T2DM with FV group. T2DM was a risk factor for prevalent VF with OR of 3.540 (IC95% 1.750-7.160). Conclusion. Our study showed a higher prevalence of T2DM in the VF group. T2DM women with VF were younger and had higher L-BMD than non-T2DM women, L-BMD did not correlate with age and VF were not distributed according to BMD-L and age. (AU)


Introducción. La diabetes es una enfermedad crónica asociada con comorbilidades importantes. La diabetes tipo 2 (DM2) se asocia con un riesgo tres veces mayor de fractura de cadera pero la asociación con fracturas vertebrales (FV) es contradictoria. Nuestro objetivo fue evaluar los factores involucrados en las FV prevalentes en mujeres adultas con y sin DM2. Materiales y métodos. Se realizó un diseño transversal y se evaluó la relación entre FV morfométrica y DM2 en mujeres adultas. Los casos fueron mujeres adultas con FV morfométricas y los controles fueron mujeres adultas sin FV. Se obtuvieron radiografías torácicas y espinales en proyecciones lateral y anteroposterior. Los valores de densidad mineral ósea (DMO) de la columna lumbar (DMO-L) se midieron por DXA. Resultados. Se observó un mayor número de mujeres con DM2 en el grupo de FV (61% frente a 31.5%). Las mujeres sin DM2 con FV eran significativamente mayores y con una DMO-L más baja que las mujeres sin DM2 sin FV. Observamos una correlación negativa entre la edad y la DMO-L (r= -0.463) en mujeres sin DM2 y FV, pero no en DM2 con FV. La DM2 fue un factor de riesgo para FV prevalente con un OR 3.540 (IC95% 1.750-7.160). Conclusión. Nuestro estudio demostró una mayor prevalencia de DM2 en el grupo de FV. Las mujeres con DM2 y FV eran más jóvenes y tenían mayor DMO-L que las mujeres sin DM2, la DMO-L no correlacionó con la edad y las FV no se distribuyeron de acuerdo a la DMO-L y edad. (AU)


Subject(s)
Humans , Female , Adult , Young Adult , Spinal Fractures/microbiology , Diabetes Mellitus, Type 2/complications , Osteoporosis/complications , Vitamin D/blood , Absorptiometry, Photon , Bone Density , Cross-Sectional Studies , Risk Factors , Spinal Fractures/chemically induced , Spinal Fractures/diagnostic imaging , Age Factors , Thiazolidinediones/therapeutic use , PPAR gamma/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Rosiglitazone/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Pioglitazone/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use
16.
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s17-s24, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057108

ABSTRACT

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.


Subject(s)
Humans , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Kidney Diseases/prevention & control , Benzhydryl Compounds/therapeutic use , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/prevention & control , Sodium-Glucose Transporter 2/therapeutic use , Canagliflozin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Glomerular Filtration Rate , Glucose/metabolism , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Kidney/drug effects , Kidney/physiopathology , Kidney/metabolism , Kidney Diseases/etiology , Kidney Diseases/metabolism
18.
Rev Assoc Med Bras (1992) ; 66(4): 458-465, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1136227

ABSTRACT

SUMMARY After metformin failure in treatment for diabetes type 2, there is no trivial option for adjuvant medication. The last two oral class medications, gliflozins and gliptins, have different mechanisms of action but have never been compared in long run studies. The aim of the present meta-analysis is to assess the overall long-term efficacy of these drugs after metformin failure. A systematic review and meta-analysis were performed, including all trials with a duration of over 2 years, comparing gliflozins or gliptins after metformin failure in type 2 diabetes. Data Sources: Pubmed (Medline), Embase, Lilacs, and the Cochrane Library from inception through July 2016 without language restrictions. The longest study period found in the literature was 4 years. We selected 1 article on empagliflozin, 1 on dapagliflozin, and 1 on saxagliptin with missing data. After one year of treatment, over 50% of the patients presented HbA1c > 7%. Efficacy rate after 4 years of empagliflozin (23%) was better than dapagliflozin (5%) and saxagliptin (7%); however, it presented statistically non-significant values for HbA1c (7.4 and 7.3% between gliflozins), and missing data for saxaglifozin. Nonetheless, empagliflozin performed better than glimepiride in the 4-year period (standardized mean difference SMD 0.4, confidence interval CI 95% 0.23 to 0.56). The failure of the secondary treatment using gliflozins occurs in less than one year of treatment (less than 50% of the patients presenting HbA1c > 7 %). Empagliflozin offered better glycemic control compared to sulfonylureas but was similar to dapagliflozin.


RESUMO Após a falha da metformina no tratamento do diabetes tipo 2, não existe uma opção trivial para a medicação adicional. Os dois últimos medicamentos de classe oral, gliflozinas e gliptinas, têm mecanismos de ação diferentes, mas nunca foram comparados em estudos de longo prazo. O objetivo da presente meta-análise é a avaliação da eficácia global em longo prazo desses medicamentos após a falha da metformina. Uma revisão sistemática e meta-análise foram realizadas, incluindo todos os ensaios com uma duração de mais de dois anos, comparando gliflozinas ou gliptinas após a insuficiência de metformina no diabetes tipo 2. Fontes de dados: PubMed (Medline), Embase, Lilacs e a Biblioteca Cochrane desde o início até julho de 2016, sem restrições de idioma. O período mais longo de estudo encontrado na literatura foi de quatro anos. Foi selecionado um artigo sobre empagliflozina, um artigo sobre dapagliflozina e um artigo sobre saxagliptina com dados faltantes. Após um ano de tratamento, mais de 50% dos pacientes apresentavam HbA1c >7%. A taxa de eficácia em quatro anos de empagliflozina (23%) foi melhor que dapagliflozina (5%) e saxagliptina (7%), porém com valores estatisticamente não significativos para HbA1c (7,4% e 7,3% entre gliflozinas) e dados ausentes para a saxaglifozina. No entanto, a empagliflozina teve um desempenho melhor do que a glimepirida no período de quatro anos (diferença média padronizada SMD 0,4, intervalo de confiança IC 95% 0,23 a 0,56). A falha do tratamento secundário com gliflozinas ocorre em menos de um ano de tratamento (menos de 50% dos pacientes com HbA1c >7%). A empagliflozina ofereceu melhor controle glicêmico em comparação com as sulfonilureias, mas semelhante à dapagliflozina.


Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Metformin , Benzhydryl Compounds , Network Meta-Analysis , Hypoglycemic Agents
19.
Arch. endocrinol. metab. (Online) ; 63(5): 478-486, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1038500

ABSTRACT

ABSTRACT Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.


Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Randomized Controlled Trials as Topic , Drug Therapy, Combination , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage
20.
Rev. méd. Chile ; 147(9): 1093-1098, set. 2019. tab
Article in Spanish | LILACS | ID: biblio-1058650

ABSTRACT

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new pharmacological alternative for the treatment of diabetes. Aim: To report our experience with the use of this type of drugs in type 2 diabetics treated in an outpatient clinic. Material and Methods: We selected 77 type 2 diabetic patients aged 59 ± 11 years (45 men) who started SGLT2i, based on the advice of their treating physician. We registered their demographic characteristics and changes in metabolic parameters, weight, blood pressure, albuminuria and adverse effects, during a follow-up of at least three months. Results: We observed a decrease of glycosylated hemoglobin A1c of 0.8 ± 1.14% (p < 0.01) and a weight decrease of 2.5 ± 2.24 kg (p < 0.01). The proportion of patients with a glycosylated hemoglobin A1c of less than 7% increased from 7.2% to 30.9% (p = 0.002). In addition, a relative decrease in albuminuria of 39.9% was observed (p = 0.07). The treatment was well tolerated with a rate of adverse effects of 21%, all of them being categorized as mild. Of these, most of them corresponded to genital mycotic infections. Conclusions: The effects observed in this study are comparable and of similar magnitude to randomized studies of SGLT2i reported in the international literature.


Subject(s)
Humans , Male , Middle Aged , Aged , Pharmaceutical Preparations , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium , Glucose , Hypoglycemic Agents/therapeutic use
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