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1.
Med Clin North Am ; 105(1): 149-174, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33246516

RESUMO

Obesity is a chronic disease caused by dysregulated energy homeostasis pathways that encourage the accumulation of adiposity, which in turn results in the development or exacerbation of weight-related comorbidities. Treatment of obesity relies on a foundation of lifestyle modification; weight loss pharmacotherapy, bariatric surgery and devices are additional tools to help patients achieve their health goals. Appropriate management of patients with obesity provides multiple metabolic benefits beyond weight loss.


Assuntos
Obesidade/terapia , Sobrepeso/terapia , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Terapia Comportamental , Dieta Redutora , Medicina Baseada em Evidências , Terapia por Exercício , Jejum , Estilo de Vida Saudável , Humanos , Obesidade/etiologia , Obesidade/fisiopatologia , Sobrepeso/etiologia , Sobrepeso/fisiopatologia , Exame Físico
2.
Eur J Endocrinol ; 183(5): R149-R166, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33107433

RESUMO

Obesity, defined by an excess of body fat impacting on health, is a complex disease resulting from the interaction between many genetic/epigenetic factors and environmental triggers. For some clinical situations with severe obesity, it has been possible to classify these obesity forms according to the molecular alterations. These include: (i) syndromic obesity, which associates severe early-onset obesity with neurodevelopmental disorders and/or polymalformative syndrome and (ii) non-syndromic monogenic obesity, due to gene variants most often located in the leptin-melanocortin pathway. In addition to severe obesity, patients affected by these diseases display complex somatic conditions, eventually including obesity comorbidities, neuropsychological and psychiatric disorders. These conditions render the clinical management of these patients particularly challenging. Patients' early diagnosis is critical to allow specialized and multidisciplinary care, with a necessary interaction between the health and social sectors. Up to now, the management of genetic obesity was only based, above all, on controlling the patient's environment, which involves limiting access to food, ensuring a reassuring daily eating environment that limits impulsiveness, and the practice of adapted, supported, and supervised physical activity. Bariatric surgery has also been undertaken in genetic obesity cases with uncertain outcomes. The context is rapidly changing, as new innovative therapies are currently being tested both for syndromic and monogenic forms of obesity. This review focuses on care management and new therapeutic opportunities in genetic obesity, including the use of the melanocortin 4 agonist, setmelanotide. The results from ongoing trials will hopefully pave the way to a future precision medicine approach for genetic obesity.


Assuntos
Cirurgia Bariátrica/tendências , Endocrinologia/tendências , Obesidade Mórbida/terapia , Obesidade/terapia , Adulto , Fármacos Antiobesidade/uso terapêutico , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Obesidade/genética , Obesidade Mórbida/genética , Síndrome , alfa-MSH/análogos & derivados , alfa-MSH/uso terapêutico
3.
Nat Commun ; 11(1): 4981, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020469

RESUMO

Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/uso terapêutico , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Polipeptídeo Inibidor Gástrico/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologia , Receptores dos Hormônios Gastrointestinais/deficiência , Receptores dos Hormônios Gastrointestinais/metabolismo
4.
Curr Opin Endocrinol Diabetes Obes ; 27(4): 194-206, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618631

RESUMO

PURPOSE OF REVIEW: Obesity is increasing in prevalence among patients with type 1 diabetes (T1D) and is associated with insulin resistance and increased cardiovascular risk. The management of obesity in this population is complicated by defects in pancreatic islet hormone secretion and the effects of exogenous insulin treatment. Here, we review the effects of antiobesity medications and adjunct-to-insulin medications on body weight in T1D. RECENT FINDINGS: There is a profound evidence gap around the use of drugs for the treatment of obesity in T1D since systematic studies have not been performed in this population. Adjunctive-to-insulin therapy with certain antihyperglycemic agents leads to modest weight loss and reductions in insulin dose in T1D. However, only pramlintide has been approved in the United States for clinical use as adjunctive therapy in T1D. SUMMARY: The growing prevalence of obesity in T1D has created an unmet need for safe and effective therapies to treat overweight and obesity in this population. Currently, antiobesity medications are used off-label for the treatment of patients with T1D. Additional studies are needed to understand the role of these medications in the management of obesity in patients with T1D.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/classificação , Peso Corporal/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Obesidade/epidemiologia , Perda de Peso/efeitos dos fármacos
5.
Obesity (Silver Spring) ; 28(7): 1171-1172, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32374528

RESUMO

Obesity treatment is highly stigmatized, mainly because of the stigma of obesity itself. The frequent withdrawal of medications, lorcaserin being the last example, contributes to this stigma, but it is also probably a reflection of it, as data suggest that the threshold for a withdrawal is lower than with other classes of drugs. Safety should always be an absolute priority for every new medication, especially when used on a chronic basis; however, the safety scrutiny given to antiobesity medications is not given for other medications, such as postmenopausal hormone therapy and central nervous system drugs for psychiatric use. The withdrawal of medications for obesity can also impact future research in the area, so we need transparency and equality. Transparency in knowing exactly what reason led to a drug being discontinued and equality in long-term safety should be a concern with any medication prescribed for chronic diseases.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Benzazepinas/efeitos adversos , Doença Crônica/tratamento farmacológico , Medicamentos sob Prescrição/uso terapêutico , Estigma Social , Fármacos Antiobesidade/uso terapêutico , Benzazepinas/uso terapêutico , Doença Crônica/epidemiologia , Humanos , Assistência de Longa Duração , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Obesidade/psicologia , Medicamentos sob Prescrição/classificação , Vigilância de Produtos Comercializados/normas , Retirada de Medicamento Baseada em Segurança , Estereotipagem , Estados Unidos/epidemiologia , United States Food and Drug Administration/normas
6.
Obesity (Silver Spring) ; 28(6): 1023-1030, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441476

RESUMO

OBJECTIVE: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon. METHODS: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively. RESULTS: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB. CONCLUSIONS: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Derivação Gástrica/métodos , Fentermina/uso terapêutico , Topiramato/uso terapêutico , Ganho de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fentermina/farmacologia , Período Pós-Operatório , Estudos Retrospectivos , Topiramato/farmacologia
7.
FP Essent ; 492: 25-29, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32383845

RESUMO

Pharmacotherapy, adjunctively with lifestyle interventions, is an option for any patient diagnosed with obesity (ie, body mass index [BMI] of 30 kg/m2 or greater) or with a BMI of 27 kg/m2 or greater and at least one coexisting condition, including type 2 diabetes, hypertension, hyperlipidemia, and sleep apnea. If the appropriate criteria are met, pharmacotherapy should be initiated for patients with overweight or obesity if lifestyle modification does not produce adequate weight loss. Lifestyle modifications should be continued and emphasized throughout treatment because it has been shown that adjunctive pharmacotherapy produces greater weight loss and weight loss maintenance than lifestyle interventions alone. Currently, five drugs are approved for weight management in adults: phentermine, orlistat, phentermine-topiramate, bupropion-naltrexone, and liraglutide. Certain drugs are approved for short-term management while others are approved for long-term management. Drug therapy should be customized to the individual patient, depending on needs, contraindications, and cost. Benefits of these drugs should be assessed regularly and a different drug should be considered if at least 5% of body weight is not lost by 3 months of therapy.


Assuntos
Fármacos Antiobesidade , Diabetes Mellitus Tipo 2 , Obesidade , Adulto , Fármacos Antiobesidade/uso terapêutico , Benzazepinas , Diabetes Mellitus Tipo 2/complicações , Humanos , Obesidade/complicações , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico
8.
Expert Opin Pharmacother ; 21(11): 1319-1328, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32292094

RESUMO

INTRODUCTION: Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions. AREAS COVERED: This review covers the history of antiobesity drugs, efficacy, and risks of currently approved drugs, limits of their usefulness in clinical practice, gaps in knowledge, methodological limitations of clinical trials, and reasons for underutilization. EXPERT OPINION: In randomized controlled trials, currently approved antiobesity drugs have yielded an average weight loss ranging from approximately 3% to 9% relative to placebo at 1 year. Inadequate inclusion of racial and ethnic minorities and men, and high dropout rates in clinical trials limit generalizability of these findings to clinical practice. Weight loss achieved with antiobesity drugs is generally associated with lowered glycemia, but improvements in blood pressure and lipid measures tend to be marginal. There is limited evidence for sustained weight loss beyond 1 year and for safety and efficacy of antiobesity drugs in children and adolescents, and in post-bariatric surgery patients. None have demonstrated reduction in major adverse cardiovascular events or other significant disease outcomes. Limited health insurance coverage and negative perceptions of physicians have hindered the utilization of antiobesity drugs.


Assuntos
Fármacos Antiobesidade , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adolescente , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Pressão Sanguínea/efeitos dos fármacos , Criança , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Uso de Medicamentos , Humanos , Estilo de Vida , Resultado do Tratamento
10.
Curr Pharm Biotechnol ; 21(11): 1099-1106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32188382

RESUMO

BACKGROUND: Chlorogenic Acid (CA) has diverse, recognized health effects. OBJECTIVE: This study aimed to explore the effects of CA on fat reduction and the underlying mechanism of these effects. MATERIALS AND METHODS: First, we established a Monosodium Glutamate (MSG)-induced obesity mouse model and subjected the mice to 4 weeks of CA gavage. Then, we established an oleic acidinduced model of human fatty liver in HepG2 cells, and administered a CA intervention to the cells for 48 h. Finally, we used Oil red O staining, biochemical detection kits, RT-PCR and Western blot analysis to evaluate the effects of CA on fat reduction and on related pathways. RESULTS: The CA treatment could reduce fat accumulation in the liver and reduce blood lipid levels. In addition, CA decreased the mRNA and protein levels of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α) and Uncoupling Protein 1 (UCP1) in the MSG-induced obesity mouse model and the oleic acid-induced HepG2 cells. CONCLUSION: Based on the above results, we deduced that CA could reduce body weight and fat deposition in vitro and in vivo and that the mechanism may be related to the PGC-1α/UCP-1 pathway. CA can be developed as a drug to lower blood lipids and to treat obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Ácido Clorogênico/farmacologia , Fígado Gorduroso/tratamento farmacológico , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/uso terapêutico , Ácido Clorogênico/uso terapêutico , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glutamato de Sódio/metabolismo , Proteína Desacopladora 1/metabolismo
11.
Tech Vasc Interv Radiol ; 23(1): 100653, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32192633

RESUMO

Obesity is a public health epidemic in the United States, with implications for patients across many organ systems. Despite improvements in understanding the pathophysiology and increasing number of therapies for obesity, its prevalence continues to rise. The purpose of this review is to provide the interventional radiologist with an understanding of (1) the epidemiology of obesity; (2) the impact of obesity on patients and the healthcare system; (3) the causes of obesity; (4) conservative management of obesity; and (5) pharmacologic management of obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Estilo de Vida Saudável , Obesidade/terapia , Comportamento de Redução do Risco , Fármacos Antiobesidade/efeitos adversos , Regulação do Apetite/efeitos dos fármacos , Dieta Saudável , Exercício Físico , Comportamento Alimentar , Humanos , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/psicologia , Fatores de Risco , Resultado do Tratamento , Perda de Peso
13.
PLoS Biol ; 18(3): e3000688, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32218572

RESUMO

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.


Assuntos
Tecido Adiposo Marrom/metabolismo , Fármacos Antiobesidade/uso terapêutico , Cumarínicos/uso terapêutico , Obesidade/prevenção & controle , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/metabolismo , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Fígado Gorduroso/prevenção & controle , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Reação de Maillard , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Propiltiouracila/toxicidade , Termogênese , Tri-Iodotironina/antagonistas & inibidores , Tri-Iodotironina/metabolismo , Ganho de Peso/efeitos dos fármacos
14.
Open Heart ; 7(1): e001003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32201580

RESUMO

Spirulina, a cyanobacteria commonly referred to as a blue-green algae, is one of the oldest lifeforms on Earth. Spirulina grows in both fresh and saltwater sources and is known for its high protein and micronutrient content. This review paper will cover the effects of spirulina on weight loss and blood lipids. The currently literature supports the benefits of spirulina for reducing body fat, waist circumference, body mass index and appetite and shows that spirulina has significant benefits for improving blood lipids.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Obesidade/tratamento farmacológico , Spirulina , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/efeitos adversos , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Humanos , Hipolipemiantes/efeitos adversos , Obesidade/diagnóstico , Obesidade/fisiopatologia , Resultado do Tratamento
15.
Rev Med Suisse ; 16(687): 573-577, 2020 Mar 25.
Artigo em Francês | MEDLINE | ID: mdl-32216179

RESUMO

Obesity is a chronic disease that requires a complex treatment. Establishing a balanced diet and regular physical activity is not always simple, especially in the long term. There are multiple factors (biological and psychological) favoring weight gain, often limiting the effectiveness of lifestyle approaches. Pharmacology offers us another therapeutic option with new molecules effective for weight loss. Bariatric surgery is also effective, but it is not without risks, especially if the patients have not been adequately prepared for this procedure. Furthermore, these approaches should always be proposed as complementary to lifestyle changes. This article summarizes the different treatments for obesity and highlights the importance of a multidisciplinary management and proper patient education.


Assuntos
Exercício Físico/fisiologia , Obesidade/prevenção & controle , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Dieta Saudável , Exercício Físico/psicologia , Humanos , Obesidade/psicologia , Perda de Peso/efeitos dos fármacos
16.
Pediatr Obes ; 15(7): e12624, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32062862

RESUMO

BACKGROUND: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor agonist could be a treatment option for adolescent obesity. OBJECTIVE: To investigate the effect of exenatide extended release on body mass index (BMI)-SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity. METHODS: Six-month, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n = 44, 10-18 years, females n = 22) with BMI-SDS > 2.0 or age-adapted-BMI > 30 kg/m2 according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended release 2 mg (n = 22) or placebo (n = 22) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention. RESULTS: Exenatide reduced (P < .05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (-2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3 ; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5), and BMI (-0.83 kg/m2 ; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; P = .06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients. CONCLUSIONS: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI reduction for the patient group.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Exenatida/uso terapêutico , Obesidade Pediátrica/tratamento farmacológico , Adolescente , Índice de Massa Corporal , Criança , Método Duplo-Cego , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Obesidade Pediátrica/metabolismo
17.
Biochem Biophys Res Commun ; 525(2): 455-461, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32107002

RESUMO

Metabolic syndrome is defined by hyperlipidemia and cardiovascular complications. We have examined whether inhibition of glycosphingolipid synthesis can interfere with metabolic syndrome in a male mouse model of type II diabetes (db/db). The db/db and control mice (C57/BL6) (n = 6) fed chow for 30 weeks received vehicle (5% Tween-80 in PBS; 100 µl), or a biopolymer-encapsulated D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (BPD) glycosphingolipid synthesis inhibitor daily via oral gavage for 6 weeks. Echocardiography revealed increased Ao-IMT in db/db mice compared to control. However, BPD decreased Ao-IMT, monohexosylceramide and dihexosylceramide, LDL, triglycerides, glucose, and raised HDL levels in db/db mice. This was due to increased gene expression of HMG-CoA reductase, LDLr, SREBP2, and bile acids: Cy7-a hydroxylase, LXR and FXR, lipoprotein lipase, VLDL receptor and PPAR. Treatment also increased the expression of superoxide dismutase-II to reduce the pro-oxidant status in these mice. We observed that decreased cholesterol levels correlated with decreased cholesterol sensing proteins e.g. NPC1 gene/protein expression and mammalian target of rapamycin (mTORC-1) and reduced body weight. Thus, glycosphingolipid synthesis inhibition is a novel approach to manage metabolic syndrome and reduce body weight in diabetic mice and with potential applications in humans.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Glicoesfingolipídeos/metabolismo , Lipogênese/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Morfolinas/uso terapêutico , Animais , Fármacos Antiobesidade/uso terapêutico , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
18.
Obesity (Silver Spring) ; 28(3): 529-536, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090517

RESUMO

OBJECTIVE: Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg. METHODS: The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE) IBT was a 56-week, randomized, double-blind, placebo-controlled, multicenter trial in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140) as an adjunct to IBT. RESULTS: At week 56, mean weight loss with liraglutide 3.0 mg plus IBT was 7.5% and 4.0% with placebo combined with IBT (estimated treatment difference [95% CI]-3.4% [-5.3% to -1.6%], P = 0.0003). Significantly more individuals on liraglutide 3.0 mg than placebo achieved ≥ 5% weight loss (61.5% vs. 38.8%; odds ratio [OR] 2.5% [1.5% to 4.1%], P = 0.0003), > 10% weight loss (30.5% vs. 19.8%; OR 1.8% [1.0% to 3.1%], P = 0.0469), and > 15% weight loss (18.1% vs. 8.9%; OR 2.3% [1.1% to 4.7%], P = 0.0311). Liraglutide 3.0 mg in combination with IBT was well tolerated, with no new safety signals identified. CONCLUSIONS: In a primary care setting, Centers for Medicare and Medicaid Services-based IBT produced clinically meaningful weight loss at 56 weeks, enhanced by the addition of liraglutide 3.0 mg.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Terapia Comportamental/métodos , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Método Duplo-Cego , Feminino , Humanos , Liraglutida/farmacologia , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Resultado do Tratamento , Estados Unidos
19.
Medicine (Baltimore) ; 99(5): e18955, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000419

RESUMO

BACKGROUND: Obesity is associated with metabolic syndrome, a condition that increases one's risk for heart disease and other conditions. The prevalence of obesity and associated diseases have steadily increased among Korean adults. The effect of the herbal medicines Daesiho-tang (DSHT) and Chowiseungcheng-tang (CST) on obesity have been reported. The purpose of this study is to evaluate the efficacy and safety of Daesiho-tang and Chowiseungcheng-tang on obese Korean women with high risk for metabolic syndrome. METHODS/DESIGN: This study is a randomized, double-blinded, placebo-controlled, multi-center, 3-arm, parallel group clinical trial. A total of 120 participants will be enrolled and randomly assigned to the Daesiho-tang group, the Chowiseungcheng-tang group, or the placebo group in a 1:1:1 ratio using an internet-based randomization system at visit 2. Each group will be administered DSHT, CST, or placebo 3 times per day for 12 weeks. The primary outcome is to evaluate the changes in mean body weight of participants in the DSHT and CST groups and compare with those in the placebo group, and determine their statistical significance, if any, after 12 weeks. The secondary outcomes are the following: changes in body fat percentage and body fat mass, changes in waist circumference, waist-to-hip ratio, and body mass index, changes in serum lipids, fasting blood sugar, blood pressure, and C-reactive proteins (CRP) levels between visit 1 and visit 5 measurements. Changes in visceral fat volume determined through abdominal computed tomography, patient-reported health outcomes surveys-the Korean version of the Obesity-related Quality of Life and the Korean version of Eating Attitudes Test. DISCUSSION: This study will provide research methodologies for evaluating the efficacy and safety of Daesiho-tang and Chowiseungcheng-tang on obese Korean women with high risk for metabolic syndrome. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02651454. Registered on 11 January 2016.Protocol version: The final approved version of the trial protocol is V1.3.(2017.11.10).


Assuntos
Medicina Tradicional Coreana , Síndrome Metabólica/tratamento farmacológico , Estudos Multicêntricos como Assunto , Obesidade/tratamento farmacológico , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Adulto , Idoso , Fármacos Antiobesidade/uso terapêutico , Feminino , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Seleção de Pacientes , Projetos Piloto , República da Coreia , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
Ann Pharmacother ; 54(7): 691-705, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31958967

RESUMO

Objective: To synthesize the evidence from systematic reviews of clinical trials investigating the effectiveness of pharmacological therapies approved by the Australian Therapeutic Goods Administration and the US Food and Drug Administration for the management of obesity in adults. Data Sources: A 3-step literature search of the MEDLINE, EMBASE, CINAHL, and PubMed databases was conducted between March and May 2019. The key terms used were obesity, pharmacological therapy, antiobesity agent, antiobesity medication, weight loss, and systematic review. Study Selection and Data Extraction: Systematic reviews that evaluated the effectiveness of pharmacological therapies for the management of obesity in patients with a body mass index of or greater than 25 kg/m2. Data Synthesis: Nine systematic reviews involving three pharmacotherapies, liraglutide, orlistat, and naltrexone-bupropion were identified. The results indicate that the pharmacotherapies reduced weight when compared with placebo. Orlistat was effective in significantly reducing fasting blood glucose, HbA1c, total cholesterol, triglycerides, and systolic and diastolic blood pressure. All reviews discussed the presence or risk of gastrointestinal adverse effects including diarrhea, vomiting, and nausea related to orlistat and liraglutide. Relevance to Patient Care and Clinical Practice: This umbrella review compares the efficacy and safety of antiobesity medications for reducing weight and a discussion on their weight loss and metabolic control to guide clinicians when prescribing medications for obesity. Conclusions: All pharmacological therapies included in this review are superior to placebo in reducing weight. Clinicians should consider patient comorbidities and risk of adverse events when recommending medications for weight loss.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Peso Corporal/efeitos dos fármacos , Bupropiona/uso terapêutico , Liraglutida/uso terapêutico , Naltrexona/uso terapêutico , Obesidade/tratamento farmacológico , Orlistate/uso terapêutico , Adulto , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Austrália , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Combinação de Medicamentos , Humanos , Liraglutida/administração & dosagem , Liraglutida/efeitos adversos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Orlistate/administração & dosagem , Orlistate/efeitos adversos
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