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1.
Rev. clín. esp. (Ed. impr.) ; 220(2): 135-138, mar. 2020.
Artículo en Español | IBECS | ID: ibc-186427

RESUMEN

Existe una asociación bidireccional entre la insuficiencia cardiaca (IC) y la diabetes mellitus tipo 2 (DM2) que hace que la combinación de ambas enfermedades en un mismo paciente haya pasado a tener un incremento exponencial. Dicha combinación, parte de múltiples causas comunes que llevan a vías fisiopatológicas que resultan en un efecto deletéreo de la DM2 sobre la IC. La consecuencia clínica inevitable es que ante dicha situación el paciente presente peor clínica y peor pronóstico que el paciente con IC sin DM2. Por todo ello debemos tener en cuenta cómo tratar la DM2 en pacientes con IC, y cómo tratar la IC en pacientes con DM2. En esta revisión se hace hincapié en los últimos datos publicados al respecto


There is a bidirectional association between heart failure (HF) and type 2 diabetes mellitus (DM2), which has resulted in an exponential increase in the combination of the 2 diseases in a single patient. This combination is one of many common causes that lead to the pathophysiological pathways resulting in the deleterious effect of DM2 on HF. The inevitable clinical consequence is that, when faced with this situation, patients present worse symptoms and a poorer prognosis than patients with HF but without DM2. We should therefore consider how to treat DM2 in patients with HF and how to treat HF in patients with DM2. In this review, we highlight the latest published data on this issue


Asunto(s)
Humanos , Insuficiencia Cardíaca/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Metformina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Insuficiencia Cardíaca/complicaciones , Hemoglobina A Glucada/análisis , Factores de Riesgo , Susceptibilidad a Enfermedades/epidemiología , Estado Prediabético/complicaciones
2.
Medicine (Baltimore) ; 99(10): e19378, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32150083

RESUMEN

BACKGROUND: Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction. The relationship between metformin therapy and cognitive function in patients with T2D is unknown. Therefore, we determined the relationship between metformin therapy and cognitive function in patients with T2D using a meta-analysis. METHODS: We systematically searched the Cochrane library, PubMed, and Embase to identify studies showing correlations, and we calculated hazard ratios (HRs). RESULTS: We identified 10 studies including 254,679 participants. Metformin significantly reduced the occurrence of cognitive dysfunction in patients with T2D (HR 0.90; 95% CI [0.88, 0.92]). Compared with other hypoglycemic drugs, sulfonylureas also improved cognitive dysfunction (HR 0.92; 95% CI [0.88, 0.95]). Thiazolidinediones gave no statistically significant improvement in cognitive dysfunction (HR 0.97; 95% CI [0.87, 1.07]). The use of insulin aggravated cognitive dysfunction (HR 1.34; 95% CI [1.24, 1.43]). In the subgroup analysis of various regions controlling for age, gender, education, diabetes course, complications, metformin administration and dosage, and follow-up time, metformin significantly improved cognitive dysfunction in patients in the Americas and Europe (HR 0.69; 95% CI [0.63, 0.74]), (HR 0.71; 95% CI [0.66, 0.76], respectively), while metformin did not significantly improve cognitive dysfunction in Asian patients (HR 0.99; 95% CI [0.96, 1.01]). CONCLUSIONS: Metformin significantly improved cognitive dysfunction in patients with T2D. Sulfonylureas also improved cognitive dysfunction. Thiazolidinediones had no significant effect on cognitive dysfunction. The use of insulin aggravated cognitive dysfunction. Metformin improved cognitive dysfunction more significantly in patients in the Americas and Europe than in Asia.


Asunto(s)
Disfunción Cognitiva/etiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/efectos adversos , Disfunción Cognitiva/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Metformina/uso terapéutico
3.
Orv Hetil ; 161(13): 491-501, 2020 Mar.
Artículo en Húngaro | MEDLINE | ID: mdl-32202151

RESUMEN

Introduction and aim: The of this research was to conduct a network meta-analysis based on a systematic literature search to compare the relative frequency of urinary tract infections using sodium-glucose cotransporter-2 (SGLT2) inhibitors combined with metformin in the therapy of type 2 diabetes. Method: MEDLINE and EMBASE databases were searched to identify publications of randomized, controlled trials investigating SGLT2 inhibitors combined with metformin in the therapy of type 2 diabetes and providing information on the frequency of urinary tract infections. Results: 10 165 unique citations were screened to identify 10 publications to be included in the network meta-analysis. The network meta-analysis showed reduced risk of urinary tract infections for low-dose ertugliflozin compared to other SGLT2 inhibitors (ertugliflozin 5 mg vs. empagliflozin 10 mg: RR: 0.606, 95% CrI: 0.264-1.415; ertugliflozin 5 mg vs. dapagliflozin 10 mg: RR = 0.853, 95% CrI: 0.301-2.285). For high-dose comparisons, empagliflozin 25 mg showed reduced risk of urinary tract infections compared to both ertugliflozin 15 mg (RR = 0.745, 95% CrI 0.330-1.610) and dapagliflozin 10 mg (RR = 0.680, 95% CrI: 0.337-1.289). The difference between active substances and their doses was not statistically significant for the relative frequency of urinary tract infections. The meta-regression revealed a statistically significant association between baseline fasting plasma glucose level and relative frequency of urinary tract infections (ß = 0.785, 95% CrI: 0.062-1.587). Conclusion: There was no statistically significant difference between SGLT2 inhibitors investigated in this study in terms of the relative frequency of urinary tract infections. This research demonstrates the applicability of network meta-analyses when assessing the relative effectiveness and safety of interventions. Orv Hetil. 2020; 161(13): 491-501.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/administración & dosificación , Metformina/uso terapéutico , Proteínas de Transporte de Sodio-Glucosa/antagonistas & inhibidores , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Infecciones Urinarias/epidemiología , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Asian Pac J Cancer Prev ; 21(3): 733-741, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32212801

RESUMEN

OBJECTIVE: To compare the Ki-67 index of endometrial cancer cells before and after treatment between the metformin and placebo group in women with endometrial cancer (EC). METHODS: This study was a randomized, double-blind, placebo-controlled trial conducting in non-diabetic women who diagnosed with endometrioid EC and had a schedule for elective surgical staging at Rajavithi Hospital between August 2018 and June 2019. Tissue specimens were obtained via endometrial curettage at the time of initial diagnosis (pre-treatment) and hysterectomy (post-treatment) to assess the value of the Ki-67 index by immunochemistry. Patients were randomly assigned into 2 groups: metformin and placebo group. Metformin 850 mg or placebo 1 tab were administered once daily for at least 7 days, starting on the first morning after recruitment until one day before surgery. Baseline characteristics (e.g., age, body mass index, co-morbidities) including surgical and pathological characteristics were recorded. The metabolic effect of metformin was also evaluated by a recording of fasting blood sugar, HbA1C and potential adverse events including nausea, vomiting, dizziness, and hypoglycemic symptom. RESULTS: A total of 49 EC patients were included in this study. Twenty-five patients were assigned to the metformin group and 24 patients were assigned to the placebo group. Baseline demographic, surgical, and pathological characteristics between the 2 groups were similar. Metformin significantly changed the Ki-67 index relative to placebo, with a mean decrease of 23.3% (p=0.001) and a mean proportional decrease of 39.1% (p=0.006) before and after treatment. Additionally, no significant differences were detected in metabolic effects and adverse events between the metformin and the placebo groups. CONCLUSION: Short-term treatment with an oral metformin significantly reduced a proliferative marker Ki-67 index in women with endometrioid EC awaiting surgical staging. This study supports the biological effect of metformin in EC and potential applications in the adjuvant treatment in EC patients.


Asunto(s)
Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/metabolismo , Metformina/uso terapéutico , Biomarcadores/análisis , Proliferación Celular , Método Doble Ciego , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad
5.
Life Sci ; 245: 117361, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32001268

RESUMEN

AIMS: Evaluation of the anti-diabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs) on Type 2 diabetic rats and compared their effect to metformin treatment. MAIN METHODS: Diabetic rats were treated with different doses of nanoparticles one time per week for 4 weeks. Fasting blood glucose level was determined for studied groups during the experimental period (30 days). At the end of the experiment, oral glucose tolerance test was carried out, serum samples were collected for biochemical assays. Then animals were sacrificed to obtain tissues for assessment of glucose transporters, insulin receptors and insulin signaling proteins. KEY FINDING: SPIONs treatment normalized fasting blood glucose and lowering insulin level in diabetic rats compared to untreated diabetic rats. SPIONs significantly ameliorate the glucose sensing and the active components of insulin signaling pathway. The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better. SIGNIFICANCE: To our knowledge, this is the first study that explores the anti-diabetic effects of SPIONs on diabetic model.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Compuestos Férricos/uso terapéutico , Glucosa/metabolismo , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Nanopartículas de Magnetita/uso terapéutico , Animales , Glucemia/análisis , Prueba de Tolerancia a la Glucosa , Masculino , Metformina/uso terapéutico , Ratas , Ratas Sprague-Dawley
7.
Eur J Endocrinol ; 182(4): 447-457, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32069218

RESUMEN

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umeå University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5ß-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Dieta Reductora/métodos , Ejercicio/fisiología , Glucocorticoides/metabolismo , Pérdida de Peso/fisiología , Adulto , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/terapia , Dieta Paleolítica , Terapia por Ejercicio/métodos , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Resistencia a la Insulina , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento
8.
Expert Opin Pharmacother ; 21(2): 207-211, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31893931

RESUMEN

Introduction: Approximately 1% of adolescents have polycystic ovary syndrome (PCOS) and almost 40-70% of these patients are overweight or obese. Obese adolescents with PCOS have more severe insulin resistance and hyperandrogenemia, a more adverse lipid profile and a worse quality of life than normal-weight adolescents with PCOS. Accordingly, weight loss is an important component of the management of these patients.Areas covered: The authors discuss the different options for weight loss in obese adolescents with PCOS. Lifestyle changes appear to be effective but adherence to this intervention is suboptimal. There are also limited data regarding the optimal diet in this population. Few small studies have evaluated the effects of pharmacotherapy in these patients. Conflicting data have been reported regarding the effects of metformin on body weight. Notably, agents that have been approved for weight loss in adults have not been evaluated in adolescents with PCOS.Expert opinion: More studies are needed to identify the most appropriate diet for obese adolescents with PCOS. Well-designed randomized controlled studies are also needed to define the safety and efficacy of pharmacotherapy in this population.


Asunto(s)
Estilo de Vida , Obesidad Pediátrica/terapia , Síndrome del Ovario Poliquístico/terapia , Adolescente , Femenino , Humanos , Hiperandrogenismo/terapia , Resistencia a la Insulina , Metformina/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de Peso
9.
Life Sci ; 243: 117276, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31926250

RESUMEN

AIMS: Chemo-resistance still was the main obstacle for AML patients, more effective and less toxic forms of therapies were desperately needed. Metformin, a classic hypoglycemic drug for diabetes recently delivered us a new identity that it exerted anti-tumor activity through suppressing mTOR in various tumors. But the anti-tumor effect of metformin in AML was not clear. METHODS: In this study, we used CCK8 assay and apoptosis assay to determine the anti-leukemia activity of metformin combined with AraC, and explore the mechanism of the joint role of Ara-C/metformin in AML. We finally used xenograft experiment in mice to determine the anti-leukemia effect of Ara-C/metformin in vivo. KEY FINDINGS: We found that metformin could synergistically sensitize AML cells to Ara-C via inhibiting mTORC1/P70S6K pathway. In vivo experiment also verified metformin in aid of Ara-C caused an obviously synergistic anti-tumor effect. SIGNIFICANCE: We firstly found the synergistic anti-tumor effect of Ara-C/metformin in AML through inhibiting mTORC1/P70S6K pathway.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Metformina/uso terapéutico , Proteínas Quinasas S6 Ribosómicas 70-kDa/antagonistas & inhibidores , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Citarabina/administración & dosificación , Sinergismo Farmacológico , Humanos , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Metformina/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Medicine (Baltimore) ; 99(2): e18708, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914078

RESUMEN

Sarcopenia is a geriatric syndrome and it impairs physical function. Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of sarcopenia. The purpose of this study is to explore characteristics of general information and metabolic factors of sarcopenia in patients with T2DM in the northeast of China, and provide information for the prevention and treatment of sarcopenia in clinical practice.Patients with T2DM aged ≥65 were recruited in Changchun from March 2017 to February 2018. Questionnaires of general information, physical examination, laboratory and imaging examination were conducted. The patients were assigned into sarcopenia group and non-sarcopenia group according to the diagnostic criteria proposed by Asian working group for sarcopenia (AWGS), and the differences between 2 groups were analyzed.A total of 132 participants were included in this study, of which, 38 (28.8%) were diagnosed with sarcopenia. 94 (71.2%) were with no sarcopenia. Logistic regression analysis showed that age (OR: 1.182, 95%CI: 1.038-1.346), trunk fat mass (TFM) (OR: 1.499, 95%CI: 1.146-1.960) and free thyroxine (FT4) (OR: 1.342, 95%CI: 1.102-1.635) were independent risk factors for sarcopenia. BMI (body mass index) (OR: 0.365, 95%CI: 0.236-0.661), exercise (OR: 0.016, 95%CI: 0.001-0.169), female (OR: 0.000, 95%CI: 0.00-0.012), metformin (OR: 0.159, 95%CI: 0.026-0.967) and TSM (trunk skeletal muscle mass) (OR: 0.395, 95%CI: 0.236-0.661) were protective factors for sarcopenia.Sarcopenia in patients with T2DM is associated with increased age, increased TFM and increased FT4 level. Regular exercise, female, metformin administrations, high BMI and increased TSM are associated with lower risk of sarcopenia.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Sarcopenia/epidemiología , Sarcopenia/fisiopatología , Factores de Edad , Anciano , Anciano de 80 o más Años , Composición Corporal/fisiología , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Ejercicio/fisiología , Femenino , Humanos , Modelos Logísticos , Masculino , Metformina/uso terapéutico , Músculo Esquelético/fisiopatología , Factores de Riesgo , Factores Sexuales , Tiroxina/sangre
11.
AAPS PharmSciTech ; 21(2): 48, 2020 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-31900731

RESUMEN

Doxorubicin and Metformin HCL is a known chemotherapeutic combination that wipes out tumors and prevents their recurrence. However, limited site specificity confines its application. Here we report Doxorubicin and Metformin HCL-loaded guar gum micro-particles prepared by emulsification cum-solidification method. Developed micro-particles were characterized as spherical shape particles with smooth surface and micro size diameter. Encapsulation of drugs in combination was confirmed by their characteristic functional groups (FT-IR), change in phase transition temperature (DSC) and X-ray diffraction pattern (XRD). Particles were observed to be stable at 25 and 5°C. The in vitro Doxorubicin and Metformin HCL release study in simulated gastric (SGF), intestinal (SIF) and colonic fluid (SCF) confirms restricted release in SGF (9.3 and 9.6%, respectively, in 2 h) and SIF (10.8 and 14.7%, respectively, in the next 3 h) and highest release in SCF (about 68 and 73.3%, respectively) in colon. Developed micro-particles showed 78% recovery in tumor volume and considerable improvement in histological changes. X-ray images confirmed good target ability of micro-particles to colon. In conclusion, the specially designed, stable micro-particles are able to target drug combination to colon and improve efficacy by ensuring maximum drug release in colon as compared with Doxorubicin and Metformin HCL combination.


Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Galactanos/administración & dosificación , Mananos/administración & dosificación , Metformina/administración & dosificación , Gomas de Plantas/administración & dosificación , Administración Oral , Animales , Doxorrubicina/metabolismo , Doxorrubicina/uso terapéutico , Femenino , Humanos , Técnicas In Vitro , Masculino , Metformina/metabolismo , Metformina/uso terapéutico , Ratas , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier
12.
Expert Opin Pharmacother ; 21(1): 121-130, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31689132

RESUMEN

Background: Vildagliptin is a dipeptidyl peptidase-4 inhibitor that reduces glycemia in patients with type 2 diabetes mellitus (T2DM). When approved in 2013, data on vildagliptin combined with >750 mg/day metformin in Japanese patients were limited. There is a need to confirm the safety and efficacy of vildagliptin in combination with oral antidiabetic drugs (OADs).Research design and methods: This 52-week post-marketing surveillance (PMS) observational study in Japanese T2DM patients evaluated the safety and efficacy of vildagliptin in combination with OADs including high-dose metformin or insulin but excluding combination with sulfonylureas alone.Results: During this survey of 3006 Japanese T2DM patients, 13.61% of patients experienced adverse events (AEs) and 2.20% reported a serious AE (SAE). The frequency of AEs/SAEs was similar when in combination with biguanides (12.93%/1.46%), metformin ≥1000 mg/day (12.92%/1.22%), metformin <1000 mg/day (12.62%/1.54%), thiazolidine derivatives (16.71%/2.86%), α-glucosidase inhibitors (13.18%/1.90%), rapid-acting insulin secretagogues  (glinides) (20.41%/5.71%), or insulin (15.87%/2.47%). The mean ± SD changes from baseline at endpoint in glycated hemoglobin and fasting blood glucose were -0.76 ± 1.27% and -23.3 ± 57.3 mg/dL, respectively, and these changes were consistent, regardless of concomitant OAD.Conclusions: Long-term vildagliptin combination therapy is safe and effective in Japanese T2DM patients in real-world settings.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Hipoglucemiantes/administración & dosificación , Vildagliptina/administración & dosificación , Anciano , Glucemia/efectos de los fármacos , Estudios de Cohortes , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Femenino , Hemoglobina A Glucada/análisis , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/uso terapéutico , Japón , Masculino , Metformina/administración & dosificación , Metformina/uso terapéutico , Persona de Mediana Edad , Vigilancia de Productos Comercializados , Compuestos de Sulfonilurea/uso terapéutico , Vildagliptina/efectos adversos
13.
Curr Diabetes Rev ; 16(2): 143-147, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30451115

RESUMEN

INTRODUCTION: The Diabetes Prevention Program study results indicated that metformin therapy was not as beneficial as a lifestyle modification for delaying the development of type 2 diabetes in individuals at high risk of the disease. A key feature in the etiology of type 2 diabetes mellitus, which appears in the prediabetic phase, is a significant deficiency, compared to healthy controls, in highly flexible poly-cis-unsaturated fatty acyl chains in membrane phospholipids. This deficiency lowers membrane flexibility, which in turn, reduces the amount of all functional Class I glucose transporters, and thereby reduces glucose-mediated ATP production. This leads to an increase in essentially saturated free fatty acid (FFA) levels for fatty-acid-mediated ATP production, which will set up a vicious cycle of raising the levels of essentially saturated FFAs and lowering the level of transmembrane glucose transport. Metformin suppresses hepatic gluconeogenesis, which reduces the plasma glucose concentration. CONCLUSION: We hypothesize that chronic metformin treatment leads to an additional increase in essentially saturated FFAs, which causes an additional rise in membrane stiffness and hypoxia. So we propose that all these metformin-mediated activities accelerated the onset of type 2 diabetes in the participants of the metformin group in the Diabetes Prevention Program study, compared to the participants of the lifestyle-intervention group in this study. We propose that the biochemical reactions, involved in the fatty-acid-mediated ATP production, play an important part in the increase of the observed essentially saturated FFA concentrations. These statements should also extend to the metformin therapy of individuals with type 2 diabetes.


Asunto(s)
Membrana Celular/efectos de los fármacos , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Grasos/metabolismo , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Estado Prediabético/metabolismo , Glucemia/metabolismo , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/terapia , Progresión de la Enfermedad , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Estilo de Vida Saludable , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Metformina/farmacología , Metformina/uso terapéutico , Estado Prediabético/sangre , Estado Prediabético/tratamiento farmacológico , Estado Prediabético/terapia , Medición de Riesgo , Factores de Riesgo
14.
Int J Cancer ; 146(3): 803-809, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30980539

RESUMEN

Metformin has been linked to improve survival of patients with various cancers. There is little information on survival of glioblastoma patients after use of metformin. We assessed the association between metformin use and survival in a pooled analysis of patient data from 1,731 individuals from the randomized AVAglio, CENTRIC and CORE trials. We performed multivariate Cox analyses for overall survival (OS) and progression-free survival (PFS) comparing patients' use of metformin at baseline and/or during concomitant radiochemotherapy (TMZ/RT). Further exploratory analyses investigated the effect of metformin with a history of diabetes and nonfasting glucose levels in relation to OS or PFS of glioblastoma patients. Metformin alone or in any combination was not significantly associated with OS or PFS (at baseline, hazard ratio [HR] for OS = 0.87; 95% confidence interval [CI] = 0.65-1.16; HR for PFS = 0.84; 95% CI = 0.64-1.10; during TMZ/RT HR for OS = 0.97; 95% CI = 0.68-1.38; HR for PFS = 1.02; 95% CI = 0.74-1.41). We found a statistically nonsignificant association of metformin monotherapy with glioblastoma survival at baseline (HR for OS = 0.68; 95% CI = 0.42-1.10; HR for PFS = 0.57; 95% CI = 0.36-0.91), but not during the TMZ/RT period (HR for OS = 0.90; 95% CI = 0.51-1.56; HR for PFS = 1.05; 95% CI = 0.64-1.73). Diabetes mellitus or increased nonfasting glucose levels were not associated with a difference in OS or PFS in our selected study population. Metformin did not prolong survival of patients with newly diagnosed glioblastoma in our analysis. Additional studies may identify patients with specific tumor characteristics that are associated with potential benefit from treatment with metformin, possibly due to metabolic vulnerabilities.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/mortalidad , Glioblastoma/mortalidad , Metformina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/terapia , Quimioradioterapia , Femenino , Glioblastoma/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Temozolomida/uso terapéutico , Adulto Joven
15.
J Assoc Physicians India ; 67(12): 44-49, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31801331

RESUMEN

Background: This study evaluated the adherence and swallowing experience with novel oval-shaped, compact-sized metformin (500 mg/1000 mg)-glimepiride (1mg/2mg) combination, sustained-release tablet (Gluformin G1/Gluformin G2 SR; GM-new-SR) in Indian patients with T2DM, previously treated with conventional metformin-glimepiride combination tablet. Methods: Patients' adherence, swallowing experience, and satisfaction were assessed at baseline and month-3 by Adherence to Refills and Medication Scale (ARMS12; adherent: ARMS12 score=12; nonadherent: ARMS12 score >12) and questionnaire based 5-point Likert scale, respectively. Safety was also assessed. Results: Of 1550 patients enrolled, 1547 (99.8%) completed the study. After 3 months of switching to GM-new-SR tablets, adherence rate increased from 4.38% to 91.1%, with concurrent reduction in mean ARMS-12 score by 6.3±4.36 (p<0.0001). Compared to baseline, all glycemic indices, HbA1c, PPG, and FPG, significantly improved (p<0.0001) in the overall population. Reduction in HbA1c levels was significant only in patients who were adherent to therapy as opposed to nonadherent patients (7.8±1.74 to 7.1±0.85, p<0.0001 vs. 7.7±1.39 to 6.7±0.77, p=0.4276). Most patients attributed ease of swallowing of GM-new-SR tablets to its modified shape (95.5%) and size (94.9%). Most patients (90.4%) were satisfied with the new tablet formulation. Size of the tablet was the most common reason for patients' nonadherence with conventional tablets, which was reported to be less frequent with GM-new-SR tablets (2.5% vs 53.4%). Conclusion: Treatment with GM-new-SR tablets significantly increased adherence and was associated with improvement in glycemic indices, which could be attributed to the compact shape and size of the new tablet formulation.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Glucemia , Deglución , Quimioterapia Combinada , Hemoglobina A Glucada , Humanos , Cumplimiento de la Medicación , Comprimidos
16.
Mayo Clin Proc ; 94(12): 2455-2466, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31806099

RESUMEN

OBJECTIVE: To investigate the factors that are associated with the effect of metformin on endothelial dysfunction in polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: From March 24, 2014, to November 18, 2016, 48 women with PCOS were randomly assigned to 1500 mg/d of metformin (N=29) or no treatment (N=13) for 3 months; 42 patients (29 in the initial treatment group and 13 in the no treatment group) completed the study. Study variables were measured at baseline and after 3 months. Participants who did not receive metformin initially were then treated with metformin for another 3 months, and study variables were measured again. Endothelial function was measured as reactive hyperemia-peripheral arterial tonometry (RH-PAT) from the index finger. RESULTS: The age and baseline endothelial function (mean ± SD) of the participants were 32.7±6.9 years and 1.8±0.5, respectively. No notable change was observed in endothelial function after 3 months with metformin compared with no treatment. However, after stratifying participants who received metformin based on baseline endothelial function, there was a significant improvement following metformin treatment in participants with abnormal baseline endothelial function (1.3±0.3 vs 1.7±0.3; P<.001) but not in those with normal baseline endothelial function (2.1±0.4 vs 2.0±0.5; P=.11). CONCLUSION: Metformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. Metformin has a direct effect on endothelial function in PCOS, and measurement of endothelial function can stratify and follow response to metformin treatment in PCOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02086526.


Asunto(s)
Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adulto , Femenino , Humanos , Manometría , Síndrome del Ovario Poliquístico/fisiopatología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
17.
BMC Infect Dis ; 19(1): 1039, 2019 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-31818258

RESUMEN

BACKGROUND: Ligands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated. METHODS: We examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC). RESULTS: Systemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to TB at 2nd month and 6th month of anti-TB treatment (ATT). RAGE ligands were increased in TB-DM individuals with bilateral and cavitary disease. sRAGE and S100A12 correlated with glycated hemoglobin levels. Within the TB-DM group, those with known diabetes (KDM) revealed significantly increased levels of AGE and sRAGE compared to newly diagnosed DM (NDM). KDM participants on metformin treatment exhibited significantly diminished levels of AGE and sRAGE in comparison to those on non-metformin regimens. CONCLUSIONS: Our data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy.


Asunto(s)
Antígenos de Neoplasias/sangre , Diabetes Mellitus/tratamiento farmacológico , Metformina/uso terapéutico , Proteínas Quinasas Activadas por Mitógenos/sangre , Proteína S100A12/sangre , Tuberculosis Pulmonar/sangre , Adulto , Anciano , Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Comorbilidad , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Femenino , Productos Finales de Glicación Avanzada/sangre , Proteína HMGB1/sangre , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Regulación hacia Arriba
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1305-1311, 2019 Nov 30.
Artículo en Chino | MEDLINE | ID: mdl-31852646

RESUMEN

OBJECTIVE: To assess the efficacy and safety of short- term intensive hypoglycemic therapy with a triple regimen consisting of metformin, sagliptin and dapagliflozin in patients with newly diagnosed type 2 diabetes mellitus with hemoglobin Alc (HbA1c) of 9%-12%. METHODS: We prospectively enrolled 58 patients with newly diagnosed type 2 diabetes, who were treated with metformin combined with sagliptin and dapagliflozin for 12 weeks on the basis of diabetic diet and regular exercise. Blood glucose was monitored during the treatment and the changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), fasting insulin (FINS), 2-hour postprandial insulin (2 hPINS), fasting C-peptide (F-CP), 2-hour postprandial C-peptide (2 hP-CP), and body weight after treatment as well as the incidence of hypoglycemia and adverse events associated with the treatment were recorded. RESULTS: Two patients withdrew from the study for intolerance of gastrointestinal reactions, and another 2 withdrew for inconvenience of access to the medicines. Fifty-four of the patients finally completed the study, including 34 male and 20 female patients. After 12 weeks of therapy, all the patients showed significant improvements in FBG, 2 hPBG, HbA1c, HOMA-beta and HOMA-IR (P < 0.001) with a mean reduction of HbA1c level by (4.19 ± 1.07)%, and the goal of HbA1c control to below 7.0% was achieved in 83.33% of the patients. The reduction of HbA1c was correlated with FBG (r=0.487, P=0.000), 2 hPBG (r=0.310, P=0.023), and HOMA-ß (r=-0.398, P=0.003). The patients had a mean body weight loss by 2.47±3.38 kg (P < 0.001) and a mean decrease of body mass index (BMI) by 0.90± 1.18 kg/m2 (P < 0.001) after the therapy. The body weight-reducing effect was associated with the patients' baseline body weight (r=0.678, P=0.000), BMI (r=0.818, P=0.000), F-CP (r=0.282, P=0.039) and HOMA-IR (r=0.297, P=0.029). During the therapy 8 patients experienced hypoglycemic symptoms (10 times, 14.81%); 3 patients were diagnosed with hypoglycemia (blood glucose ≤3.9 mmol/L, 3 times), and the overall incidence of hypoglycemia was 5.56%. No serious hypoglycemia or infections of the urinary and reproductive systems occurred in these patients. CONCLUSIONS: Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia. The combined therapy can effectively improve ß-cell insulin secretion function, and is suitable for treatment of newly diagnosed type 2 diabetic patients with high blood glucose.


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2 , Glucósidos/uso terapéutico , Metformina/uso terapéutico , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Hemoglobina A Glucada , Humanos , Hipoglucemiantes , Insulina , Masculino , Resultado del Tratamiento
19.
PLoS Med ; 16(12): e1002999, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31877127

RESUMEN

BACKGROUND: Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication-including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)-can be added to achieve this. However, treatment effects of intensification with the medications on the risk of severe hypoglycemia (SH), cardiovascular disease (CVD), and all-cause mortality are uncertain. Study aim was to compare the risks of all-cause mortality, CVD, and SH among patients with T2DM on Met-SU dual therapy intensified with DPP4i, insulin, or TZD. METHODS AND FINDINGS: We analyzed a retrospective cohort data of 17,293 patients with T2DM who were free from CVD and on Met-SU dual therapy and who were intensified with DPP4i (n = 8,248), insulin (n = 6,395), or TZD (n = 2,650) from 2006 to 2017. Propensity-score weighting was used to balance out baseline covariates across groups. Hazard ratios (HRs) for all-cause mortality, CVD, and SH were assessed using Cox proportional hazard models. Mean age of all patients was 58.56 ± 11.41 years. All baseline covariates achieved a balance across the 3 groups. Over a mean follow-up period of 34 months with 49,299 person-years, cumulative incidences of all-cause mortality, SH, and CVD were 0.061, 0.119, and 0.074, respectively. Patients intensified with insulin had higher risk of all-cause mortality (HR = 2.648, 95% confidence interval [CI] 2.367-2.963, p < 0.001; 2.352, 95% CI 2.123-2.605, p < 0.001) than those intensified with TZD and DPP4i, respectively. Insulin users had the greatest risk of SH (HR = 1.198, 95% CI 1.071-1.340, p = 0.002; 1.496, 95% CI 1.342-1.668, p < 0.001) compared with TZD and DPP4i users, respectively. Comparing between TZDs and DPP4i, TZDs were associated with a higher risk of SH (HR = 1.249, 95% CI 1.099-1.419, p < 0.001) but not all-cause mortality (HR = 0.888, 95% CI 0.776-1.016, p = 0.084) or CVD (HR = 1.005, 95% CI 0.915-1.104, p = 0.925). Limitations of this study included the lack of data regarding lifestyle, drug adherence, time-varying factors, patients' motivation, and cost considerations. A limited duration of patients intensifying with TZD might also weaken the strength of study results. CONCLUSIONS: Our results indicated that, for patients with T2DM who are on Met-SU dual therapy, the addition of DPP4i was a preferred third-line medication among 3 options, with the lowest risks of mortality and SH and posing no increased risk for CVD events when compared to insulin and TZD. Intensification with insulin had the greatest risk of mortality and SH events.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemia/mortalidad , Insulina/efectos adversos , Metformina/efectos adversos , Adulto , Anciano , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Diabetes Mellitus Tipo 2/mortalidad , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Hipoglucemia/complicaciones , Hipoglucemiantes/efectos adversos , Incidencia , Insulina/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Compuestos de Sulfonilurea/efectos adversos , Tiazolidinedionas/uso terapéutico , Resultado del Tratamiento
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(10): 1128-1136, 2019 Oct 28.
Artículo en Chino | MEDLINE | ID: mdl-31857506

RESUMEN

OBJECTIVE: To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L (P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.


Asunto(s)
Antipsicóticos/efectos adversos , Diabetes Mellitus Tipo 2 , Dislipidemias , Metformina/uso terapéutico , Glucemia , Método Doble Ciego , Dislipidemias/inducido químicamente , Dislipidemias/tratamiento farmacológico , Humanos , Hipoglucemiantes
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