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PURPOSE: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. METHODS: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. RESULTS: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. CONCLUSIONS: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.
Assuntos
Diabetes Mellitus Experimental , Glibureto , Ratos , Masculino , Animais , Glibureto/efeitos adversos , Hipoglicemiantes/efeitos adversos , Ácido Gálico/efeitos adversos , Estreptozocina/efeitos adversos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Córnea/patologia , Água/efeitos adversos , GlicemiaRESUMO
OBJECTIVE: To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus. METHODS: Studies published in English, in the last 10 years, in the databases MEDLINE®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords "Gestational diabetes", "Glyburide", "Metformin" and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide. RESULTS: The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036). CONCLUSION: The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.
Assuntos
Diabetes Gestacional , Metformina , Glicemia , Diabetes Gestacional/tratamento farmacológico , Feminino , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Recém-Nascido , Insulina/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico , GravidezRESUMO
ABSTRACT Objective To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus. Methods Studies published in English, in the last 10 years, in the databases MEDLINE®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords "Gestational diabetes", "Glyburide", "Metformin" and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide. Results The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036). Conclusion The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/tratamento farmacológico , Metformina/efeitos adversos , Metformina/uso terapêutico , Glicemia , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.
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Compostos Benzidrílicos/uso terapêutico , Glicemia/efeitos dos fármacos , Doenças das Artérias Carótidas/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glibureto/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Vasodilatação/efeitos dos fármacos , Adulto , Idoso , Compostos Benzidrílicos/efeitos adversos , Biomarcadores/sangue , Glicemia/metabolismo , Brasil , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Quimioterapia Combinada , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Glucosídeos/efeitos adversos , Glibureto/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
O diabetes mellitus gestacional (DMG) é uma complicação que atinge o metabolismo da gestante, resultando em intolerância à glicose e consequente hiperglicemia, originada pela insuficiência de insulina materna. Este estudo tem como objetivo identificar os tratamentos disponíveis e mais utilizados para o DMG. Trata-se de um uma revisão de literatura, feita a partir de 22 referências, acerca dos tratamentos para o DMG. As bases de dados escolhidas foram Google Acadêmico, UpToDate, SciELO e o acervo da Universidade do Planalto Catarinense. Estudos apontam a insulina humana NPH e regular como a principal escolha, quando comparada aos seus análogos, apesar de ainda existirem muitas controvérsias quanto ao início do tratamento, o esquema terapêutico e os ajustes das doses. Pesquisas têm demonstrado bons resultados sobre a eficácia e a segurança dos hipoglicemiantes orais gliburida e metformina no tratamento de gestantes diabéticas, mas é evidente a necessidade de mais estudos para confirmar a efetividade deles e garantir um bom desenvolvimento do concepto. Concluiu-se que o controle dietético e o exercício físico são a primeira opção de tratamento para o DMG. Todavia, caso a euglicemia não seja atingida, opta-se pelo tratamento medicamentoso por meio da insulinoterapia ou hipoglicemiantes orais, o que possibilita a redução da incidência dos efeitos adversos ao binômio materno-fetal.(AU)
Gestational diabetes mellitus (DMG) is a complication that affects the pregnant woman's metabolism, resulting in glucose intolerance and consequent hyperglycemia, caused by insufficient maternal insulin. This study aims to identify the available and most used treatments for DMG. This is a literature review, based on 22 references, about treatments for Gestational Diabetes; the databases chosen were Google Scholar, UpToDate, SciELO and the collection of the Universidade do Planalto Catarinense. Studies point to human insulin NPH and regular as the main choice when compared to its analogues, although there are still many controversies about the beginning of treatment, therapeutic scheme and dose adjustments. Researches have shown good results on the efficacy and safety of oral hypoglycemic agents glyburide and metformin in the treatment of diabetic pregnant women, but it is evident the need for further studies to confirm their effectiveness and to guarantee a good development of the fetus. It was concluded that dietary control and physical exercise are the first treatment option for DGM. However, if euglycemia is not achieved, drug treatment is chosen through insulin therapy or oral hypoglycemic agents, which makes it possible to reduce the incidence of adverse effects to the maternal-fetal binomial.(AU)
Assuntos
Humanos , Feminino , Gravidez , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/terapia , Diabetes Mellitus/tratamento farmacológico , Exercício Físico , Bases de Dados Bibliográficas , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêuticoRESUMO
BACKGROUND: Recent findings on the benefits of glibenclamide as a neuroprotective drug have started a new era for prospective studies on sulfonylureas. The effect of glibenclamide blocking the Sur1-Trpm4 channel was examined in models of subarachnoid hemorrhage and stroke, with findings of significantly reduced tight-junction abnormalities, resulting in less edema formation and considerably reduced transsynaptic apoptosis of hippocampal neurons and significantly ameliorated impairments in spatial learning. Based on these data, we plan a clinical trial to establish evidence of glibenclamide as an adjunct treatment in aneurysmal subarachnoid hemorrhage. METHODS: An estimated 80 patients meeting the inclusion criteria of radiological confirmatory evidence of an aneurysmal subarachnoid hemorrhage, age 18-70 years, and presentation of less than 96 h from the ictus will be allocated randomly into two groups, one receiving 5 mg daily oral intake of glibenclamide for 21 days and another control group receiving a placebo. The study's primary outcome is the modified Rankin scale (mRS) after 6 months, as favorable (mRS 0-2) or unfavorable (mRS 3-6). The secondary outcomes will be late cognitive status, assessed after 6 months by psychological tests (the Short Form Health Survey Questionnaire and the Montreal Cognitive Assessment), as well as death at 6 months, delayed cerebral ischemia and occurrence of serious adverse events due to study medication. DISCUSSION: There is a growing interest in the scientific community regarding glibenclamide in brain edema and traumatic brain injury, but with very little of this interest targeting spontaneous brain hemorrhage, especially aneurism rupture. Positive outcomes are expected for the treatment patients, especially in language and memory preservation, as has been shown in experimental models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03569540 . Retrospectively registered on 26 June 2018.
Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Glibureto/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Adolescente , Adulto , Idoso , Encéfalo/fisiopatologia , Brasil , Método Duplo-Cego , Feminino , Glibureto/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/fisiopatologia , Hemorragia Subaracnóidea/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
AIM: Strict blood glucose control in the treatment of diabetes can sometimes lead to hypoglycemia. The main aim of this study was to assess the prevalence of hypoglycemia among patients receiving sulfonylureas alone, or in combination with metformin, for the treatment of Type 2 Diabetes Mellitus (T2DM) in Argentina. METHODS: This is a real life, multi-center, retrospective, and cross-sectional study based on clinical chart reviews including cross-sectional data, and evaluation of patient questionnaires of T2DM patients (>30 years), treated with sulfonylureas alone or in combination with metformin, during a routine clinic visit in 16 medical centers across Argentina. Socio-demographic and clinical parameters were collected from medical records, as well as hypoglycemic events from both the medical records and the patient questionnaires. The glycated hemoglobin (HbA1c) levels were obtained from medical records as well as a blood test. RESULTS: The study included a total of 397 patients with a mean age of 62.5 years, diagnosed for 9.9 years, and 54.2% male. Mean HbA1c levels were 8.1%, (65mmol/mol) at enrolment, with 36.4% being in control (HbA1c<7%, (53mmol/mol). Patients with HbA1c<7%, (53mmol/mol) were significantly older, diagnosed at older age, and had lower triglyceride levels. Almost 50% reported hypoglycemic episodes that were mostly mild, and with women more likely to report them. The large majority (86%) were on combined metformin and sulfonylureas, most commonly Glibenclamide (48.6%). Patients on combined therapy were significantly younger and more likely to have uncontrolled diabetes. CONCLUSIONS: This study demonstrated that out of a sample of 397 patients with T2DM treated with sulfonylureas alone or in combination with metformin in Argentina, around 50% of them reported symptoms of hypoglycemia induced by sulfonylureas, and one third of them achieved target HbA1c<7% levels.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Compostos de Sulfonilureia/efeitos adversos , Idoso , Argentina/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Gerenciamento Clínico , Quimioterapia Combinada , Feminino , Glibureto/administração & dosagem , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/administração & dosagem , Metformina/uso terapêutico , Pessoa de Meia-Idade , Prevalência , Fatores Socioeconômicos , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/uso terapêuticoRESUMO
OBJECTIVE: To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA). RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value â¼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model. RESULTS: Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null. CONCLUSIONS: Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.
Assuntos
Arritmias Cardíacas/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Compostos de Sulfonilureia/efeitos adversos , Disfunção Ventricular/epidemiologia , Idoso , Arritmias Cardíacas/induzido quimicamente , Causas de Morte , Morte Súbita Cardíaca/etiologia , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/epidemiologia , Feminino , Glipizida/efeitos adversos , Glipizida/uso terapêutico , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Compostos de Sulfonilureia/uso terapêutico , Estados Unidos/epidemiologia , Disfunção Ventricular/induzido quimicamente , Disfunção Ventricular/complicaçõesRESUMO
Drug-drug interactions between canagliflozin, a sodium glucose co-transporter 2 inhibitor, and glyburide, metformin, and simvastatin were evaluated in three phase-1 studies in healthy participants. In these open-label, fixed sequence studies, participants received: Study 1-glyburide 1.25 mg/day (Day 1), canagliflozin 200 mg/day (Days 4-8), canagliflozin with glyburide (Day 9); Study 2-metformin 2,000 mg/day (Day 1), canagliflozin 300 mg/day (Days 4-7), metformin with canagliflozin (Day 8); Study 3-simvastatin 40 mg/day (Day 1), canagliflozin 300 mg/day (Days 2-6), simvastatin with canagliflozin (Day 7). Pharmacokinetic parameters were assessed at prespecified intervals. Co-administration of canagliflozin and glyburide did not affect the overall exposure (maximum plasma concentration [Cmax ] and area under the plasma concentration-time curve [AUC]) of glyburide and its metabolites (4-trans-hydroxy-glyburide and 3-cis-hydroxy-glyburide). Canagliflozin did not affect the peak concentration of metformin; however, AUC increased by 20%. Though Cmax and AUC were slightly increased for simvastatin (9% and 12%) and simvastatin acid (26% and 18%) following coadministration with canagliflozin, compared with simvastatin administration alone; however, no effect on active 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitory activity was observed. There were no serious adverse events or hypoglycemic episodes. No drug-drug interactions were observed between canagliflozin and glyburide, metformin, or simvastatin. All treatments were well-tolerated in healthy participants.
Assuntos
Canagliflozina/administração & dosagem , Glibureto/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Metformina/farmacocinética , Sinvastatina/farmacocinética , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Argentina , Disponibilidade Biológica , Biotransformação , Canagliflozina/efeitos adversos , Esquema de Medicação , Interações Medicamentosas , Feminino , Glibureto/administração & dosagem , Glibureto/efeitos adversos , Glibureto/sangue , Meia-Vida , Voluntários Saudáveis , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/sangue , Masculino , Taxa de Depuração Metabólica , Metformina/administração & dosagem , Metformina/efeitos adversos , Metformina/sangue , Pessoa de Meia-Idade , Modelos Biológicos , Sinvastatina/administração & dosagem , Sinvastatina/efeitos adversos , Sinvastatina/sangue , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Cardiovascular disease, endothelial dysfunction, and oxidative stress are common complications among patients with type 2 diabetes (T2DM). In addition to the average blood glucose concentration, glycemic variability may be an important factor for the development of chronic diabetes complications. Patients with T2DM are treated with various types of oral glucose-lowering drugs. Exercise is considered to benefit the health of both healthy and unhealthy individuals, which has been confirmed by a number of scientific research studies in which the participants' health improved. Our general aim in this study will be to evaluate glucose variability after submaximal exercise test in patients receiving treatment with either vildagliptin or glibenclamide. The specific aims of this study are to evaluate the oxidative stress, endothelial function, and metabolic and cardiovascular responses to exercise under treatment with vildagliptin or glibenclamide. All these responses are important in patients with T2DM. METHODS/DESIGN: This study is a PROBE (Prospective, Randomized, Open-label, Blinded-Endpoint) design clinical trial. The estimated sample needed is 20 patients with T2DM. In addition to the routine treatment (metformin), patients will receive a second drug orally for 12 weeks: the METV group will receive metformin plus vildagliptin (50 mg twice daily), and the METG group will receive metformin plus glibenclamide (5 to 10 mg twice daily.). Before and after intervention, evaluation of glycemic variability, endothelial function, oxidative stress, and metabolic and cardiovascular response will be performed at rest, during and after a submaximal exercise test (30 minutes, with an intensity based at 10% under the heart rate at the second threshold). DISCUSSION: In addition to drug treatment, exercise is recommended for treatment of glycemic control in patients with T2DM, especially for its beneficial effects on blood glucose and HbA1c. Few studies have determined the effects of the association between exercise and oral glucose-lowering drugs. The study will be conducted to assess the metabolic and cardiovascular responses at rest, and during and after submaximal exercise in patients receiving one of two oral glucose-lowering drugs (vildagliptin or glibenclamide). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01867502 study release date: May-17-2013.