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1.
Expert Rev Clin Pharmacol ; 13(1): 53-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770497

RESUMO

Introduction: Obesity poses a significant increase in morbidity and mortality and thus five anti-obesity drugs have been approved currently by US FDA. Several phase 3 trials have shown a significant improvement in cardio-metabolic profile including significant weight reduction with these agents compared to placebo.Areas covered: We systematically searched the database of PubMed, Embase, The Cochrane Library and The ClinicalTrials.gov up to 30 September 2019 and retrieved all the randomized controlled trials (RCTs) that were conducted with these five drugs for ≥1 year and explicitly reported their efficacy versus placebo. Subsequently, we have conducted the meta-analysis to primarily study the effect of these anti-obesity drugs on weight reduction. We additionally reviewed the effect of these drugs on other cardio-metabolic parameters including key adverse events.Expert opinion: This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ∆ -3.07 Kg, 95% CI, -3.76 to -2.37), phentermine plus topiramate (N = 2985; ∆ -9.77 Kg; 95% CI, -11.73 to -7.81), lorcaserin (N = 16,856; ∆ -3.08 Kg; 95% CI, -3.49 to -2.66), naltrexone plus bupropion (N = 3239; ∆ -4.39 Kg; 95% CI, -5.05 to -3.72) and liraglutide (N = 4978; ∆ -5.25 Kg; 95% CI, -6.17 to -4.32), compared to placebo (all p < 0.00001).


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Fármacos Antiobesidade/efeitos adversos , Humanos , Obesidade/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Expert Opin Investig Drugs ; 29(1): 63-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31847611

RESUMO

Introduction: Obesity is compounded by a neurobiology that is resistant to weight loss. Therefore, the development of pharmacotherapies to address the pathology underlying the dysregulation of energy homeostasis is critical.Areas covered: This review examines selected clinical trial evidence for the pharmacologic treatment of obesity and provides an expert opinion on anti-obesity drug development. The article includes the outcomes of anti-obesity medications that have been evaluated in clinical trials but have not yet received approval from the U.S. Food and Drug Administration. The mechanisms of action of glucagon-like peptide-1 agonists and co-agonists, diabetes medications being investigated for weight loss, and medications acting on the central nervous system as well as peripherally are reviewed. A search was conducted on PubMed using the terms 'Obesity AND Medications' restricted to clinical trials reported in English. Using similar terms, a search was also conducted on ClinicalTrials.gov.Expert opinion: The goal of anti-obesity therapy is finding compounds that are effective and have minimal side effects. Combining medications targeting more than one of the redundant mechanisms driving obesity increases efficacy. However, targeting peripheral mechanisms to overcome the trickle-down effects of centrally acting drugs may be the key to success in treating obesity.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Desenvolvimento de Medicamentos , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Metabolismo Energético/fisiologia , Humanos , Obesidade/fisiopatologia , Perda de Peso/efeitos dos fármacos
3.
Medicine (Baltimore) ; 98(47): e18060, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764835

RESUMO

OBJECTIVE: A retrospective chart review was conducted to explore the effect of Gambisan, a granular extract of novel herbal medicine, for short-term (≤16 weeks) weight loss in adults who are overweight and those with obesity. METHODS: Outpatients of Kyung Hee University Korean Medicine Hospital (Seoul, Korea) who took Gambisan and underwent bioelectric impedance analysis were selected (Jan 2011 to Dec 2015); their electronic medical records and clinical charts were retrospectively reviewed. The effectiveness of Gambisan was primarily evaluated by comparing body weight (BW) at baseline and endpoint, using paired t tests; the safety of Gambisan was evaluated on the basis of adverse events (AEs) experienced by patients. RESULTS: Two hundred five patients were included in this study. The study population exhibited a significant reduction in BW (73.69 ±â€Š14.49 kg to 69.01 ±â€Š13.20 kg, P < .001) as well as percentage body fat (37.38 ±â€Š5.38% to 34.50 ±â€Š5.83%, P < .001). Moreover, 111 (54.1%) patients achieved modest weight loss (≥5%), while 35 (17.1%) achieved ≥10% weight loss. Furthermore, Gambisan induced significant reduction of BW in all subgroups (body mass index, sex, prescribed duration, and dosage). Among 139 patients with available data, 79 (56.8%) reported loss-of-appetite. In addition, 120 (mostly mild) AEs were reported in 69 (49.6%) patients, and the most frequent AEs were nausea, palpitation, and insomnia. DISCUSSION: Despite limitations in interpreting the results of this retrospective medical record review, Gambisan induced statistically and clinically meaningful weight loss with a tolerable level of AEs. Based on the findings of this review, further well-designed clinical trials are warranted.


Assuntos
Sobrepeso/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Perda de Peso/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Estudos Retrospectivos , Fatores de Tempo
4.
Medicine (Baltimore) ; 98(45): e17922, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702673

RESUMO

BACKGROUND: The prevalence of excessive body weight has rapidly increased worldwide over the past decades; however, medications are intended for moderately and severely obese patients and are associated with side effects. As an alternative approach, the use of traditional herbal medicines has gained increasing popularity among overweight individuals in recent years in East Asia. HT048 is an herbal extract of Citrus unshiu and Crataegus pinnatifida, and HT077 is an herbal extract of Nelumbo nucifera and Prunus persica. These 4 herbs have been used widely for body weight reduction in China and Korea. The aims of this trial are to investigate whether HT048 and HT077 are effective at reducing body fat and weight in overweight adults, and to determine the safety of HT048 and HT077. METHODS/DESIGN: A double-blind, randomized, placebo-controlled, 3-arm parallel group trial will be conducted in adults with a body mass index (BMI) of 25 to <30 kg/m. A total of 120 eligible participants will be randomized in a 1:1:1 ratio to receive either HT048 (1000 mg), HT077 (400 mg), or matching placebo twice daily for 12 weeks, and will be monitored for an additional 4-week follow-up period after the treatment. All participants will be assessed for efficacy and safety of the investigational product at baseline and weeks 4, 8, 12, and 16. The primary endpoint is the change in body fat mass and percent body fat measured by dual-energy X-ray absorptiometry at week 12 from the baseline. The secondary efficacy variables are abdominal fat area measured by computed tomography, body fat mass and percent body fat measured by bioelectrical impedance analysis, body weight, BMI, and serum lipids and adipocytokines concentrations. Safety will be evaluated on the basis of reported adverse events, abnormal laboratory results, vital signs, and physical examination findings. DISCUSSION: This is a first-in-human trial of HT048 and HT077 to assess the efficacy and safety in overweight subjects. The results will provide high-quality evidence of the therapeutic benefits of HT048 and HT077 for weight management and the prevention of obesity. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0004271) Registered September 2, 2019.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Sobrepeso/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , República da Coreia
5.
J Biochem Mol Toxicol ; 33(11): e22400, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593355

RESUMO

Inflammatory bowel disease (IBD) is a continual ailment condition which engrosses the entire alimentary canal. The IBD can be primarily distinguished into two forms, ulcerative colitis, and Crohn's disease. The major symptoms of IBD include pustules or abscesses, severe abdominal pain, diarrhea, fistula, and stenosis, which may directly affect the patient's quality of life. A variety of mediators can stimulate the circumstances of IBD, some examples include infections by microbes such as bacteria, perturbation of the immune system and the surrounding environment of the intestines. Severe colitis was stimulated in the experimental animals through administering 4% dextran sulfate sodium (DSS) which is mixed in water ad libitum for 6 days. Eriocitrin (30 mg/kg) was then administered to the experimental animals followed by the induction of severe colitis to evaluate the therapeutic prospective of eriocitrin against the colon inflammation stimulated by DSS. In this study, eriocitrin (30 mg/kg) demonstrated significant (P < .05) attenuation activity against the DSS-stimulated severe colitis in experimental animals. Eriocitrin counteracted all of the clinical deleterious effects induced by DSS, such as body-weight loss, colon shortening, histopathological injury, accretion of infiltrated inflammatory cells at the inflamed region and the secretion of inflammatory cytokines. The results clearly showed that eriocitrin effectively attenuated DSS-induced acute colitis in experimental animals.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/farmacologia , Flavanonas/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Citrus/química , Colo/efeitos dos fármacos , Colo/patologia , Ciclo-Oxigenase 2/análise , Citocinas/metabolismo , Modelos Animais de Doenças , Flavanonas/administração & dosagem , Inflamação/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Peroxidase/metabolismo , Extratos Vegetais/administração & dosagem , Índice de Gravidade de Doença , Perda de Peso/efeitos dos fármacos
6.
Int J Clin Pract ; 73(11): e13399, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397946

RESUMO

AIMS: To evaluate in a real-world setting the effectiveness of two drugs, orlistat and liraglutide, in patients with overweight or obesity and insufficient weight loss (WL) after a lifestyle modification programme. METHODS: Retrospective, observational cohort study comparing clinical outcomes of orlistat 120 mg three times a day and liraglutide (up to 3 mg daily) in adult patients with BMI ≥30 kg/m2 or ≥27 kg/m2 with at least a weight-related comorbidity who had failed to lose at least 5% of their weight after 6 months of lifestyle modification. The co-primary end-points, assessed at 3-6 months and at the end of the follow-up, were weight change from baseline, proportion of patients who lost at least 5% of their baseline weight and adjusted differences in WL between both drugs. RESULTS: Five hundred patients, 400 in the group of orlistat (age 47.0, weight 107.8 kg) and 100 in the group of liraglutide (age 51.9 years, weight 105.1 kg), were included. Treatment with both drugs significantly reduced weight, fasting plasma glucose, systolic BP, low-density lipoprotein-cholesterol and alanine transaminase over a median follow-up period of 7 months. WL with liraglutide (-7.7 kg) was significantly greater than that observed with orlistat (-3.3 kg), and more individuals lost at least 5% of their baseline weight with liraglutide (64.7%) than with orlistat (27.4%). Rates of prediabetes significantly decreased with liraglutide in comparison to orlistat. CONCLUSIONS: In this real-world study, liraglutide showed a greater effectiveness in WL compared with orlistat and improved several obesity-associated metabolic and cardiovascular risk factors.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Orlistate/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Lactonas/uso terapêutico , Estilo de Vida , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Orlistate/efeitos adversos , Sobrepeso/tratamento farmacológico , Estudos Retrospectivos , Perda de Peso/efeitos dos fármacos
7.
Medicina (Kaunas) ; 55(7)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336940

RESUMO

Background and Objectives: The controversy about the impact of vitamin D supplementation on weight loss treatment was observed in several randomized controlled trials (RCTs). This meta-analysis investigates the effects of vitamin D supplementation (cholecalciferol or ergocalciferol) on weight loss through holistic measurements of Body Mass Index (BMI), weight and waist circumference. Materials and Methods: Google Scholar, WOS, PubMed and Scopus were explored to collect relevant studies. The selected articles focused on vitamin D supplementation in overweight and obese individuals with different conditions. Eleven RCTs were included into this meta-analysis with a total of 947 subjects, with a mean of the follow-up from 1 to 12 months and different vitamin D interventions (from 25,000 to 600,000 IU/monthly of cholecalciferol). Results: The meta-analyzed mean differences for random effects showed that cholecalciferol supplementation deceases the BMI by -0.32 kg/m2 (CI95% -0.52, -0.12 kg/m2, p = 0.002) and the waist circumference by -1.42 cm (CI95% -2.41, -0.42 cm, p = 0.005), but does not statistically affect weight loss -0.43 kg (CI95% -1.05, +0.19 kg, p = 0.17). Conclusions: This meta-analysis lays the foundation for defining the potential clinical efficacy of vitamin D supplementation as a potential therapeutic option for weight loss programs, but further studies are needed to confirm the validity of these findings and delineate potential underlying mechanisms.


Assuntos
Vitamina D/farmacologia , Perda de Peso/efeitos dos fármacos , Índice de Massa Corporal , Suplementos Nutricionais , Humanos , Obesidade/psicologia , Obesidade/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/psicologia , Programas de Redução de Peso/métodos , Programas de Redução de Peso/normas
8.
Bull Exp Biol Med ; 167(3): 351-355, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346872

RESUMO

In type 1 diabetes mellitus, the levels of insulin and C-peptide decrease at the periphery and in CNS. C-peptide potentiates the regulatory effects of insulin. We studied the effects of single and repeated (over 7 days) individual and combined nasal administration of C-peptide (10 µg/day) and insulin (20 µg/day) on activity of Akt kinase and kinase-3ß-glycogen synthase (GSK3ß), the components of 3-phosphoinositide pathway, in the hypothalamus of intact rats and rats with mild streptozotocin-induced type 1 diabetes mellitus. Phosphorylation of Akt kinase at Thr308 and Ser473 (stimulation) and GSK3ß at Ser9 (inhibition) was evaluated. In diabetes, phosphorylation of Akt kinase and, to a lesser extent, GSK3ß, is reduced. A single injection of insulin or C-peptide and insulin increased this process. Long-term combined treatment with C-peptide and insulin normalized activity of Akt kinase and GSK3ß in diabetic rats, treatment with insulin alone produced less pronounced effect; monotherapy with C-peptide was ineffective. Intranasal co-administration of C-peptide and insulin effectively stimulates the insulin system in the hypothalamus that is weakened at diabetes mellitus type 1, which can be used in the treatment of this disease.


Assuntos
Peptídeo C/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipotálamo/metabolismo , Insulina/farmacologia , Fosfatidilinositóis/metabolismo , Administração Intranasal , Animais , Peptídeo C/administração & dosagem , Sinergismo Farmacológico , Índice Glicêmico/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Masculino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Estreptozocina , Perda de Peso/efeitos dos fármacos
9.
Nutrients ; 11(7)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277301

RESUMO

The edible seaweed Gelidium elegans (GEE) is known to inhibit adipocyte differentiation. However, there has been no report on its effects in humans. In this study, we investigated whether GEE reduces body weight or fat mass in obese or overweight individuals. A total of 78 participants were randomly assigned to the test (GEE extract 1000 mg/day) and placebo groups at a 1:1 ratio, and treated for 12 weeks. At six or 12 weeks after randomization, they were evaluated for anthropometric parameters, biomarkers, and body composition. Changes in body weight and fat mass between the two groups was significantly different, as determined using ANCOVA adjusted for baseline, calorie intake, and physical activity. Body weight and fat mass were significantly decreased by GEE after 12 weeks but increased in the placebo group. Moreover, although not significant, triglyceride levels tended to decrease after GEE intake. There was no significant difference in other laboratory biomarkers between the two groups. Taken together, these results suggested that GEE significantly reduced body weight, especially fat mass, in overweight or obese individuals.


Assuntos
Adiposidade/efeitos dos fármacos , Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Obesidade/tratamento farmacológico , Alga Marinha/química , Perda de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/isolamento & purificação , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Nutrients ; 11(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277416

RESUMO

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop 'functional' foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or 'satiety' peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating 'thresholds' of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin 'satiety' peptides for weight loss remains a significant challenge.


Assuntos
Regulação do Apetite , Ingestão de Alimentos , Metabolismo Energético , Comportamento Alimentar , Hormônios Peptídicos/metabolismo , Resposta de Saciedade , Perda de Peso , Fármacos Antiobesidade/administração & dosagem , Colecistocinina/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Infusões Parenterais , Masculino , Hormônios Peptídicos/administração & dosagem , Peptídeo YY/metabolismo , Transdução de Sinais , Perda de Peso/efeitos dos fármacos
11.
J Cancer Res Clin Oncol ; 145(9): 2365-2373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280347

RESUMO

AIMS AND METHODS: This multicenter retrospective study aims to evaluate the correlations between Body Weight Loss (BWL), Body Mass Index (BMI) and clinical outcomes (ORR, PFS, and OS) of advanced gastric cancer (aGC) patients treated with second-line ramucirumab-based therapy in a "real-life" setting. RESULTS: From December 2014 to October 2018, 101 consecutive aGC patients progressed to a first-line chemotherapy were treated with ramucirumab alone (10.9%) or in combination with paclitaxel (89.1%). Median BMI was 21.2 kg/m2 and mBWL since first-line treatment commencement was 4.5%. Among 53 patients who underwent primary tumor resection (PTR), 73.6% experienced BWL, while 26.4% did not experience BWL (p = 0.0429). Patients who underwent PTR had a significantly higher probability of experiencing BWL (yes vs no) [OR = 2.35 (95% CI 1.02-5.42), p = 0.0439]. Among the 89 evaluable patients, ORR was 26.9% (95% CI 17.2-40.1). At a median follow-up of 17.3 months, mPFS was 5.4 months (95% CI 3.6-6.8) and mOS was 8.7 months (95% CI 7.3-11.9). In the multivariate analysis, only ECOG-PS and BMI were confirmed independent predictors for shorter PFS [HR = 1.69 (95% CI 1.01-2.82), p = 0.04] [HR = 1.97 (95% CI 1.12-3.46), p = 0.01] and OS [HR = 1.69 (95% CI 1.01-2.83), p = 0.04] [HR = 2.08 (95% CI 1.17-3.70), p = 0.01]. CONCLUSION: Efficacy of ramucirumab is confirmed in this "real-life" analysis. BWL seems not to have correlations with clinical outcomes in these patients, while BMI and ECOG-PS remain major prognostic factors. A possible explanation for the lack of prognostic effect of BWL might be the proportion of patients subjected to PTR in this series (52.5%).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Índice de Massa Corporal , Neoplasias Gástricas/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Quimioterapia Adjuvante , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento , Perda de Peso/fisiologia
12.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(6): 376-384, jun.-jul. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-182854

RESUMO

Introduction and objectives: The worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity. Liraglutide (LRG), a glucagon-like peptide-1 receptor agonist, can reduce body weight. This study assessed the metabolic efficacy of LRG in real-world clinical practice. Methods: An observational, retrospective cohort study including patients treated with LRG for at least one year (187 patients). Anthropometric and metabolic variables, a composite endpoint, factors predicting response to LRG, and cardiovascular risk over time were assessed. A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values. Results: HbA1c levels and weight significantly decreased in the first 12 weeks, and the decrease persisted at 12 and 24 months in all subgroups studied. Mean weight and HbA1c decreases after 24 months were 8.5kg and 1.7% respectively. HbA1c values <7% were achieved by 42% of patients at 12 months and by 40% at 24 months. Treatment with LRG allowed for reduction in insulin dose. No serious adverse events were noted. Cardiovascular risk decreased from high to moderate-low. Conclusions: Under standard clinical practice conditions, LRG achieved a better metabolic response than seen in clinical trials. Efficacy at 12 weeks of treatment is a good predictor of response. LRG allows for delaying or reducing insulin dose by improving both weight and glucose control. Cardiovascular risk improved


Introducción y objetivos: La prevalencia mundial de diabetes mellitus tipo 2 aumenta junto a la de la obesidad. Liraglutida (LRG), un agonista del receptor del péptido similar al GLP1, es un fármaco antidiabético capaz de reducir peso. Evaluamos en práctica clínica de vida real su eficacia metabólica. Método: Estudio de cohorte observacional retrospectivo. Se incluyeron los pacientes tratados al menos durante un año con LRG (187 pacientes). Evaluamos variables antropométricas, metabólicas, objetivos combinados, factores predictivos de respuesta y evolución del riesgo cardiovascular. Se construyó un modelo de efectos mixtos lineales de estructura bivariante para investigar la relación tiempo-dependiente entre el peso y los valores de HbA1c. Resultados: Descenso significativo de los valores de HbA1c y peso en las primeras 12 semanas de tratamiento, mantenido a los 12 y 24 meses, en todos los subgrupos estudiados. Reducción media de peso y HbA1c tras 24 meses de tratamiento de 8,5 kg y 1,7%. El valor de HbA1c fue <7% en 42% de pacientes a los 12 meses, 40% a los 24 meses. El tratamiento con LRG permitió reducir la dosis de insulina. No registramos eventos adversos graves. El riesgo cardiovascular mejoró. Conclusiones: Bajo condiciones de práctica clínica habitual la respuesta metabólica a LRG resultó mejor que la observada en ensayos clínicos. La eficacia a las 12 semanas de tratamiento es un buen predictor de respuesta. LRG permite retrasar o reducir la insulinoterapia. Los pacientes mejoraron su riesgo cardiovascular


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Liraglutida/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos , Liraglutida/metabolismo , Estudos Retrospectivos , Estudos de Coortes , Antropometria , Insulina/uso terapêutico
13.
Nutrients ; 11(6)2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31159504

RESUMO

BACKGROUND: In the treatment of obesity/metabolic syndrome, dietary measures traditionally focus on reducing carbohydrate/fat-related caloric intake. The possibility that changes in potassium consumption may be related to the achieved weight loss has not been previously explored. METHODS: Sixty-eight participants, with a mean age of 51.6 ± 11.0 years (F/M-30/38), who fulfilled the ATPIII criteria for the metabolic syndrome (MS) were enrolled into a 1-year intensive multidisciplinary program. Nutritional recommendation consisted of a moderate low calorie/high protein Mediterranean diet. Baseline assessment included clinical and biochemical profiling, and body composition. Nutritional components were registered over 7 days before and at the end of 1 year of treatment. RESULTS: Mean baseline body mass index (BMI) was 35 ± 4 kg/m², which declined by 9.4 ± 0.1% after one year of combined intervention. Linear stepwise regression analysis revealed that 45% of the predicted variance of the % decline in BMI was related to increased consumption of dietary potassium (ß = -0.865) and caproic acid (ß = -0.423) and reduction in the consumption of dietary vitamin B6 (ß = 0.542), calcium (ß = 0.335), total carbohydrates (ß = 0.239) and total caloric intake (ß = 0.238; p < 0.001). Notably, the strongest correlate of the decline in BMI was the increase in dietary potassium intake (ß = -0.865). Subjects whose achieved decrease in BMI was above the average (n = 30) increased potassium intake by 25% as compared to an increase in dietary potassium intake of only 3% by those whose decline in BMI was below the average (n = 36; p < 0.05). The change in dietary potassium was related to the percent increase in dietary protein (r = 0.433; p < 0.001). CONCLUSION: An increase in dietary potassium consumption is a previously unrecognized predictor of the achieved reduction in BMI in a weight-loss-oriented multidisciplinary intervention in obesity/MS. Prospective trials are underway to confirm this post-hoc finding.


Assuntos
Síndrome Metabólica/dietoterapia , Potássio na Dieta/administração & dosagem , Perda de Peso/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Clin Obes ; 9(4): e12323, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183988

RESUMO

To assess the effectiveness of liraglutide 3.0 mg in post-bariatric surgery patients, and to determine whether this would differ based on the type of bariatric surgery. One hundred seventeen post-bariatric surgery patients from the Wharton Medical Clinic were analysed. Changes in weight while taking liraglutide 3.0 mg were examined for all patients, and by three types of bariatric surgery-Roux-en-Y gastric bypass, gastric banding and gastric sleeve. Patients primarily underwent Roux-en-Y gastric bypass (n = 53, 45.3%) or gastric banding (n = 50, 42.7%). Over 7.6 ± 7.1 months taking liraglutide 3.0 mg, patients lost a statistically significant amount of weight (-6.3 ± 7.7 kg, P < .05) regardless of the type of surgery they had (P > .05). This decrease in weight remained significant after 1-year of taking liraglutide 3.0 mg (P < .05). Nausea was the most prevalent side effect, reported by 29.1% patients. While options for excess weight management in post-bariatric surgery patients are limited, results of this study suggest that post-bariatric surgery patients can lose a significant amount of weight while taking liraglutide 3.0 mg regardless of the type of surgery they had. Further, similar to non-surgical populations, post-bariatric surgery patients taking liraglutide 3.0 mg may experience gastrointestinal side effects such as nausea and can continue to lose weight up to 1 year.


Assuntos
Liraglutida/administração & dosagem , Obesidade Mórbida/tratamento farmacológico , Obesidade Mórbida/cirurgia , Perda de Peso/efeitos dos fármacos , Adulto , Cirurgia Bariátrica , Índice de Massa Corporal , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia
15.
Medicina (B Aires) ; 79(2): 115-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048277

RESUMO

Both total caloric intake and consumption of free sugars is higher than recommended. This situation contributes, among many other factors, to the increase of overweight and obesity in the population. To maintain the sweet taste of foods and beverages while reducing the caloric content and the amount of free sugars in said products, many people choose to replace sugary products in their diet for options containing noncaloric sweeteners. This change in their dietary choice is accompanied by an increasing number of consultations with health professionals about the effects that non-caloric sweeteners could have on their body weight. Results reported in different scientific publications seem contradictory in relation to this topic: some of them, showing a positive association between the consumption of non-caloric sweeteners and energy intake and body weight, while others reporting that the consumption of these additives -in replacement of sugar- may lead to a reduction in caloric intake and body weight. The main objective of this article is to review the available evidence on the consumption of non-caloric sweeteners in relation to body weight, thus providing another tool for health professionals to make nutritional recommendations based on the best available evidence.


Assuntos
Peso Corporal/efeitos dos fármacos , Adoçantes não Calóricos/farmacologia , Obesidade/prevenção & controle , Índice de Massa Corporal , Açúcares da Dieta/efeitos adversos , Ingestão de Energia/efeitos dos fármacos , Humanos , Perda de Peso/efeitos dos fármacos
16.
Ecotoxicol Environ Saf ; 180: 123-129, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082575

RESUMO

1-Nitropyrene (1-NP), a typical nitrated polycyclic aromatic hydrocarbon, is widely distributed in the environment and is well known for its mutagenic effects. Recently, we found that gestational 1-NP exposure induced fetal growth restriction. In this study, we further evaluated the effect of in utero 1-NP exposure on postnatal growth and neurobehavioral development in the offspring. Pregnant mice were administered with 1-NP (10 µg/kg) by gavage daily in late pregnancy (GD13-GD17). The body weight of each offspring was measured from PND1 to 12 weeks postpartum. Exploration and anxiety related activities were detected by open-field test at 6 weeks postpartum. Learning and memory were assessed by Morris Water Maze at 7 weeks postpartum. And depressive-like behaviors were estimated by sucrose preference test at 10 weeks postpartum. Significant body weight reduction was observed in 1-NP-exposed female offspring at PND1, PND14 and PND21 while the lower body weight was only found at PND1 for 1-NP-exposed male offspring. Exploration and anxiety activities at puberty, and depressive-like behavior in adulthood were not disturbed in offspring prenatally exposed to 1-NP. Interestingly, spatial learning and memory ability at puberty was impaired in females but not in males prenatally exposed to 1-NP. These findings suggest that gestational 1-NP exposure delays postnatal growth and impaired neurobehavioral development in a gender-dependent manner.


Assuntos
Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Mutagênicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Pirenos/toxicidade , Animais , Feminino , Masculino , Memória/efeitos dos fármacos , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Fatores Sexuais , Aprendizagem Espacial/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
17.
Nutrients ; 11(5)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109078

RESUMO

Stroke is one of the leading causes of death worldwide and while there is increasing evidence that a Mediterranean diet might decrease the risk of a stroke, the effects of dietary fat composition on stroke outcomes have not been fully explored. We hypothesize that the brain damage provoked by a stroke would be different depending on the source of dietary fat. To test this, male C57BL/6J mice were fed for 4 weeks with a standard low-fat diet (LFD), a high-fat diet (HFD) rich in saturated fatty acids (HFD-SFA), an HFD containing monounsaturated fatty acids (MUFAs) from olive oil (HFD-OO), or an HFD containing MUFAs from olive oil plus polyunsaturated fatty acids (PUFAs) docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) (HFD-OO-ω3). These mice were then subjected to transient middle cerebral artery occlusion (tMCAo). Behavioural tests and histological analyses were performed 24 and/or 48 h after tMCAo in order to elucidate the impact of these diets with different fatty acid profiles on the ischemic lesion and on neurological functions. Mice fed with HFD-OO-ω3 displayed better histological outcomes after cerebral ischemia than mice that received an HFD-SFA or LFD. Furthermore, PUFA- and MUFA-enriched diets improved the motor function and neurological performance of ischemic mice relative to those fed with an LFD or HFD-SFA. These findings support the use of DHA/EPA-omega-3-fatty acid supplementation and olive oil as dietary source of MUFAs in order to reduce the damage and protect the brain when a stroke occurs.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Azeite de Oliva/farmacologia , Animais , Antioxidantes/metabolismo , Comportamento Animal , Dieta Hiperlipídica/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ingestão de Alimentos , Ácido Eicosapentaenoico/administração & dosagem , Marcha , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Artéria Cerebral Média , Azeite de Oliva/administração & dosagem , Perda de Peso/efeitos dos fármacos
18.
J Med Food ; 22(7): 741-751, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120370

RESUMO

The prevalence of obesity is expanding rapidly worldwide, making the disease a global burden with limited treatment options. The current obesity drug development trends suggest the possibility of reducing weight and reverse metabolic disturbances of obesity by controlling appetite. In this study, we screened more than 8000 plants from our plant library for the cannabinoid (CB1) receptor antagonists and identified Morus alba as a lead medicinal plant. Kuwanon G and Albanin G were isolated and identified from root-barks of Morus alba with 92% and 96% CB1 receptor ligand binding inhibitory activity, respectively. The bioflavonoid standardized extract was tested in the acute food intake study in rats at oral doses of 250 and 500 mg/kg for its appetite suppression activity. Diet-induced obesity in the C57BL/6J mice was used to evaluate the long-term food intake reduction activity and effect on the weight loss administered orally at 250 and 500 mg/kg for 7 weeks. Statistically significant and dose-dependent reduction in food intake was observed in both acute and long-term studies for the extract. Food intake reductions of 58.6% and 44.8% at 250 mg/kg and 50.1% and 44.3% at 500 mg/kg were observed at 1 and 2 h postfood provision, respectively. A 20% reduction in daily calorie intake was observed in the long-term study. Obese mice treated with the high dose of Morus root-bark extract showed 10.4 g (22.5%) and 7.1 g (16.5%) loss in body weight compared with the vehicle-treated obese animals (at week 7) and baseline, respectively. Statistically significant reductions in biochemical markers and visceral fat deposit were also observed. These results demonstrated that Morus alba extracts enriched in Kuwanon G, and Albanin G could be used alone to control appetite, manage body weight, and improve metabolic syndromes.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Apetite/efeitos dos fármacos , Morus/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Animais , Fármacos Antiobesidade/química , Ingestão de Alimentos/efeitos dos fármacos , Flavonoides/administração & dosagem , Flavonoides/análise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia , Casca de Planta/química , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Perda de Peso/efeitos dos fármacos
19.
Cell Mol Neurobiol ; 39(6): 783-797, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115733

RESUMO

Among gliomas types, glioblastoma is considered the most malignant and the worst form of primary brain tumor. It is characterized by high infiltration rate and great angiogenic capacity. The presence of an inflammatory microenvironment contributes to chemo/radioresistance, resulting in poor prognosis for patients. Recent data show that thiazolidinones have a wide range of pharmacological properties, including anti-inflammatory and antiglioma activities. Nanocapsules of biodegradable polymers become an alternative to cancer treatment since they provide targeted drug delivery and could overcome blood-brain barrier. Therefore, here we investigated the in vitro antiglioma activity and the potential in vivo toxicity of 2- (2-methoxyphenyl) -3- ((piperidin-1-yl) ethyl) thiazolidin-4-one-loaded polymeric nanocapsules (4L-N). Nanocapsules were prepared and characterized in terms of particle size, polydispersity index, zeta potential, pH, molecule content and encapsulation efficiency. Treatment with 4L-N selectively decreased human U138MG and rat C6 cell lines viability and proliferation, being even more efficient than the free-form molecule (4L). In addition, 4L-N did not promote toxicity to primary astrocytes. We further demonstrated that the treatment with sub-therapeutic dose of 4L-N did not alter weight, neither resulted in mortality, toxicity or peripheral damage to Wistar rats. Finally, 4L as well as 4L-N did not alter makers of oxidative damage, such as TBARS levels and total sulfhydryl content, and did not change antioxidant enzymes SOD and CAT activity in liver and brain of treated rats. Taken together, these data indicate that the nanoencapsulation of 4L has potentiated its antiglioma effect and does not cause in vivo toxicity.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Nanocápsulas/química , Piperidinas/toxicidade , Piperidinas/uso terapêutico , Polímeros/química , Tiazolidinas/toxicidade , Tiazolidinas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Biomarcadores Tumorais/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Glioma/sangue , Glioma/patologia , Humanos , Luz , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/síntese química , Piperidinas/química , Polímeros/síntese química , Ratos Wistar , Tiazolidinas/síntese química , Tiazolidinas/química , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Testes de Toxicidade , Perda de Peso/efeitos dos fármacos
20.
Curr Obes Rep ; 8(3): 284-291, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31124035

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to emphasize the pivotal role of glucagon-like peptide 1 (GLP-1) in tackling the parallel epidemics of obesity and type 2 diabetes (T2DM). RECENT FINDINGS: GLP-1-based therapies and in particular GLP-1 receptor agonists (GLP-1 RA) have proven to be effective in lowering blood glucose and decreasing weight. GLP-1 RA not only mitigate these significant medical burdens but also result in weight loss and weight loss independent factors that decrease cardiovascular disease (CVD) and microvascular complications of T2DM, such as diabetic nephropathy. GLP-1-based therapies are critical for a patient-centered approach in choosing appropriate pharmacotherapy for T2DM and obesity while also taking into consideration comorbidities, such as cardiovascular and chronic kidney diseases.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Obesidade/metabolismo , Animais , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Obesidade/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Perda de Peso/efeitos dos fármacos
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