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Emerging drugs for obesity therapy

Published on Mar 1, 2009in Arquivos Brasileiros De Endocrinologia E Metabologia
· DOI :10.1590/S0004-27302009000200019
Maria Teresa Zanella19
Estimated H-index: 19
(UNIFESP: Federal University of São Paulo),
Fernando Flexa Ribeiro Filho8
Estimated H-index: 8
(UNIFESP: Federal University of São Paulo)
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Abstract
Central obesity have an important impact on the development of risk factors for coronary heart disease, including dislipidemia, glucose intolerance, insulin resistance and hypertension. These factors contribute to building cardiovascular (CV) disease as a major cause of death. The approach to obesity therapy should be designed to reduce CV risk and mortality. Diet and lifestyle changes remain the cornerstones of therapy for obesity, but the resultant weight loss is often small and long-term success is uncommon and disappointing. Drug therapy is considered for individuals with a body mass index greater than 30 kg/m2 or ranging from 25 to 30 kg/m2 if they have comorbid conditions. Antiobesity agents can be helpful to some patients in achieving and maintaining meaningful weight loss, but yet our pharmaceutical tools are of limited effectiveness considering the magnitude of the problem. At the present, only two drugs, orlistat and sibutramine, are approved for long-term treatment of obesity and promote no more than 5 to 10% of weight loss. Rimonabant, a cannabinoid-1 receptor antagonist, was withdrawn from the market because of concerns about its safety, including risk of suicidal and seizures, although very effective in promoting clinically meaningful weight loss, reduction in waist circumference, and improvements in several metabolic risk factors, rimonabant, a cannabinoid-1 receptor antagonist was withdrawn from the market because it concerns about its safety, including risk of suicidal and seizures. Fortunately, recent fundamental insights into the neuroendocrine mechanisms regulating body weight provide an expanding list of molecular targets for novel, rationally designed antiobesity drugs. In this review, the therapeutic potential of some antiobesity molecules in the development will be analyzed based on an understanding of energy homeostasis.
  • References (47)
  • Citations (17)
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References47
Newest
Published on Jan 14, 2009in The Journal of Neuroscience 6.07
Marciane Milanski17
Estimated H-index: 17
,
Giovanna R. Degasperi10
Estimated H-index: 10
+ 13 AuthorsHilton Kenji Takahashi6
Estimated H-index: 6
In animal models of diet-induced obesity, the activation of an inflammatory response in the hypothalamus produces molecular and functional resistance to the anorexigenic hormones insulin and leptin. The primary events triggered by dietary fats that ultimately lead to hypothalamic cytokine expression and inflammatory signaling are unknown. Here, we test the hypothesis that dietary fats act through the activation of toll-like receptors 2/4 and endoplasmic reticulum stress to induce cytokine expres...
548 Citations Source Cite
Published on Dec 1, 2008in International Immunopharmacology 3.36
Jaegyu Hwang8
Estimated H-index: 8
(KNU: Kyungpook National University),
Long Tai Zheng13
Estimated H-index: 13
(KNU: Kyungpook National University)
+ 2 AuthorsKyoungho Suk40
Estimated H-index: 40
(KNU: Kyungpook National University)
Abstract Glia cells are regarded as a mediator of neuroinflammation releasing pro-inflammatory cytokines and nitric oxide in the central nervous system. Microglia and astrocytes have been reported to play an important role in the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. m -Chlorophenylpiperazine ( m -CPP) is used clinically to manipulate serotonergic function, though its precise mechanisms of actions are not well understood. m -CPP alters syn...
13 Citations Source Cite
Published on Nov 1, 2008in Endocrine Practice 4.15
Rajat Bhushan5
Estimated H-index: 5
,
Karen Elkind-Hirsch15
Estimated H-index: 15
+ 3 AuthorsOry Marrioneaux3
Estimated H-index: 3
Objective: To evaluate the effect of exenatide therapy on cardiometabolic risk factors and anthropometric parameters in patients with metabolic syndrome.Methods: From June 2005 to June 2007, we performed a retrospective analysis of data extracted from the records of adult patients with metabolic syndrome being treated with exenatide. Diagnosis of any type of diabetes mellitus was exclusionary. Patients were initiated on exenatide therapy, 5 mcg, 1 hour before their morning and evening meals for ...
20 Citations Source Cite
Published on Aug 1, 2008in Endocrinology 3.80
Paty K. Picardi9
Estimated H-index: 9
(State University of Campinas),
Vivian C. Calegari11
Estimated H-index: 11
(State University of Campinas)
+ 7 AuthorsMario J.A. Saad59
Estimated H-index: 59
(State University of Campinas)
Protein tyrosine phosphatase (PTP1B) has been implicated in the negative regulation of insulin and leptin signaling. PTP1B knockout mice are hypersensitive to insulin and leptin and resistant to obesity when fed a high-fat diet. We investigated the role of hypothalamic PTP1B in the regulation of food intake, insulin and leptin actions and signaling in rats through selective decreases in PTP1B expression in discrete hypothalamic nuclei. We generated a selective, transient reduction in PTP1B by in...
89 Citations Source Cite
Published on Nov 29, 2007in BMJ 27.60
Diana Rucker7
Estimated H-index: 7
(U of A: University of Alberta),
Raj Padwal44
Estimated H-index: 44
(U of A: University of Alberta)
+ 2 AuthorsDavid C.W. Lau28
Estimated H-index: 28
(U of C: University of Calgary)
Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status. Design Updated meta-analysis of randomised trials. Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006. Studies reviewed Double blind randomised placebo controlled trials o...
597 Citations Source Cite
Published on Nov 1, 2007in The Lancet 59.10
Robin Christensen44
Estimated H-index: 44
(Frederiksberg Hospital),
Pernelle Kruse Kristensen2
Estimated H-index: 2
(UCPH: University of Copenhagen)
+ 2 AuthorsA. Astrup92
Estimated H-index: 92
(UCPH: University of Copenhagen)
Summary Background Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. Methods We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and...
666 Citations Source Cite
Published on Aug 15, 2007in The Journal of Clinical Psychiatry 4.02
Kishore M. Gadde25
Estimated H-index: 25
,
Gretchen M. Yonish3
Estimated H-index: 3
+ 1 AuthorsH. Ryan Wagner45
Estimated H-index: 45
Objective: Zonisamide and bupropion have been investigated for weight reduction in obese adults. We conducted a preliminary study comparing the effect on body weight of the combination of these 2 drugs versus zonisamide monotherapy. Method: This was a 12-week, randomized, open-label, parallel-group comparison of 2 active interventions conducted from October 2003 to June 2004. Eighteen obese women (mean [SE] body mass index of 36.8 [1.2] kg/m 2 ) were randomly assigned to receive the combination ...
71 Citations Source Cite
Published on Aug 1, 2007in Diabetes 7.20
Daniela M. Tsukumo10
Estimated H-index: 10
(State University of Campinas),
Marco A. Carvalho-Filho15
Estimated H-index: 15
(State University of Campinas)
+ 8 AuthorsLício A. Velloso59
Estimated H-index: 59
(State University of Campinas)
Obesity is associated with insulin resistance and a state of abnormal inflammatory response. The Toll-like receptor (TLR)4 has an important role in inflammation and immunity, and its expression has been reported in most tissues of the body, including the insulin-sensitive ones. Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals. He...
677 Citations Source Cite
Published on Aug 1, 2007in The Journal of Clinical Endocrinology and Metabolism 5.61
Louis J. Aronne34
Estimated H-index: 34
(Cornell University),
Ken Fujioka30
Estimated H-index: 30
(Scripps Health)
+ 6 AuthorsChristian Weyer55
Estimated H-index: 55
(Amylin Pharmaceuticals)
Context: In previous 1-yr trials, treatment with pramlintide (120 μg), an analog of the β-cell hormone amylin, induced sustained reductions in A1C and body weight in insulin-using subjects with type 2 diabetes. Objective: To assess the potential of pramlintide as an antiobesity agent, we assessed the weight effect, safety, and tolerability of pramlintide in non-insulin-treated obese subjects with and without type 2 diabetes at doses greater than previously studied. Design/Setting: We performed a...
108 Citations Source Cite
Published on May 1, 2007in The Journal of Clinical Endocrinology and Metabolism 5.61
Ira Gantz14
Estimated H-index: 14
(MSD: Merck & Co.),
Ngozi Erondu13
Estimated H-index: 13
(MSD: Merck & Co.)
+ 11 AuthorsHaiyuan Zhu3
Estimated H-index: 3
(MSD: Merck & Co.)
Context: The gastrointestinal peptide hormone, peptide YY3–36 (PYY3–36), is implicated to be a postprandial satiety factor. Objective: The aim of this study is to assess the safety, tolerability, and efficacy of intranasal PYY3–36 to induce weight loss in obese patients. Design: The study was designed as a randomized, 2-wk, single-blind placebo run-in followed by a 12-wk double-blind, placebo-controlled treatment period. Setting: The study was set within a private and institutional practice. Pat...
116 Citations Source Cite
Cited By17
Newest
Published on Jan 1, 2017in The Journal of Clinical Pharmacology 2.92
Nele Plock2
Estimated H-index: 2
(Takeda Pharmaceutical Company),
Leon Bax1
Estimated H-index: 1
+ 3 AuthorsMarc Pfister22
Estimated H-index: 22
(University of Basel)
The presented analysis was performed to characterize the relationship between treatment-related early (week 4) and longer term (3-6 months) weight loss to understand the potential utility of 4-week proof-of-mechanism studies in the early decision-making process during clinical development of new antiobesity compounds. A regression-based meta-analysis was performed leveraging publically available clinical outcomes data to (1) characterize the within-trial relationship between treatment-related ea...
2 Citations Source Cite
Published on Feb 28, 2015
Neda Nozari2
Estimated H-index: 2
,
Akram Pourshams32
Estimated H-index: 32
,
Marjan Mokhtare
Background: Obesity was a dangerous chronic disease. Physicians recommended drug therapy just in a few of obese patients in spite of many health risks. Weight control can be improved comorbidities of obesity like hyperlipedemia, hyperinsulinoma, acanthosis nigricans and hypertension. Materials and Methods: This article reviewed the available original and review literatures which had been published in English in websites of Google scholar and Pub Med with keywords drug, obesity and adults during ...
Published on Sep 3, 2014
AAIMS: To estimate the prevalence of overall and central obesity, and associated factors in adults in southern Brazil. METHODS: A cross-sectional, population-based study was conducted among adults living in Tubarao, State of Santa Catarina, Brazil, between November 2011 and June 2012. Participants were interviewed, and anthropometric measurements were taken. The interview assessed socio-demographic data, levels of physical activity, alcohol consumption, smoking, dietary habits and clinical data....
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Published on Sep 1, 2014in Social Science & Medicine 3.09
Objetivos: Estimar a prevali?½ncia de obesidade geral, obesidade central e fatores associados em adultos de uma cidade na regii?½o Sul do Brasil.Mi?½todos: Estudo transversal de base populacional com adultos residentes em Tubari?½o, Santa Catarina, de novembro de 2011 a junho de 2012. Os participantes foram entrevistados e submetidos i?½ antropometria. A entrevista avaliou dados sociodemogri?½ficos, atividade fi?½sica, consumo de i?½lcool, tabagismo, hi?½bitos alimentares (passos da alimentai?½i...
Published on Aug 1, 2013
José Hernández Rodríguez3
Estimated H-index: 3
,
Manuel E. Licea Puig7
Estimated H-index: 7
,
Lizet Castelo Elías-Calles3
Estimated H-index: 3
Introduccion: a traves del uso de la farmacoterapia en el paciente obeso se ha intentado obtener perdidas de peso, mayores y mas rapidas que las reportadas con los metodos convencionales de tratamiento, lo que sin dudas facilita una disminucion objetiva de la morbilidad y mortalidad observada en los pacientes con este problema de salud. Objetivos: describir los aspectos generales del tratamiento farmacologico en el paciente obeso y mencionar algunos de los medicamentos usados con este fin. Desar...
Published on Jan 1, 2013in American Journal of Therapeutics 1.13
Joselyn Rojas12
Estimated H-index: 12
,
Miguel Ángel Aguirre Echanove16
Estimated H-index: 16
+ 1 AuthorsBermúdez1
Estimated H-index: 1
5 Citations Source Cite
Swati Jain3
Estimated H-index: 3
(Defence Institute of Physiology and Allied Sciences),
Saroj Kumar Verma2
Estimated H-index: 2
(Defence Institute of Physiology and Allied Sciences)
+ 1 AuthorsSom Nath Singh16
Estimated H-index: 16
(Defence Institute of Physiology and Allied Sciences)
Abstract: The appetite suppressing property of Sibutramine is well reported. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced in male Sprague Dawley rats by its short term supplementation. The effect of the drug on the regulatory hormones and biochemical variables was studied at an oral dose of 10 mg/kg body weight. There was a decrease in food intake of rats by 35.5% in comparison to their basal food intake as well as unt...
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Published on Jun 1, 2011in Journal of Natural Remedies
Shiv Kumar3
Estimated H-index: 3
,
K. R. Alagawadi3
Estimated H-index: 3
The present study was aimed to screen the possible antiobesity effects of ethanol extract of Alpinia galanga rhizomes in cafeteria diet fed obese rats. Obesity was induced in albino rats by feeding cafeteria diet daily for 6 weeks in addition to normal diet. The ethanol extract of rhizomes was administered at a daily dose of 500 mg/kg orally for 6 weeks. Body weight and food intake was measured initially and then every week thereafter. On day 42, serum glucose, lipids and leptin levels were esti...
3 Citations Source Cite
Published on Mar 22, 2011in Current Neuropharmacology 4.57
João R. Araújo16
Estimated H-index: 16
,
Fátima Martel27
Estimated H-index: 27
During the last 50 years the global pandemic of obesity and associated life-threatening co-morbidities strongly promoted the development of anti-obesity pharmacotherapy. Sibutramine is an anti-obesity drug that in conjunction with lifestyle modifications reduces food intake and body weight. This may result from several effects: inhibition of presynaptic reuptake of monoaminergic neurotransmitters in the central nervous system, thereby suppressing appetite, induction of an increase in anorexigeni...
19 Citations Source Cite
Published on Mar 1, 2011in Expert Opinion on Therapeutic Targets 4.62
Anna Maria Malfitano20
Estimated H-index: 20
(UNISA: University of Salerno),
Ciaglia Elena13
Estimated H-index: 13
(UNISA: University of Salerno)
+ 3 AuthorsMaurizio Bifulco19
Estimated H-index: 19
(UNISA: University of Salerno)
Introduction: Recent studies have shown that the endocannabinoid system (ECS) could offer an attractive antitumor target. Numerous findings suggest the involvement of this system (constituted mainly by cannabinoid receptors, endogenous compounds and the enzymes for their synthesis and degradation) in cancer cell growth in vitro and in vivo. Areas covered: This review covers literature from the past decade which highlights the potential of targeting the ECS for cancer treatment. In particular, th...
40 Citations Source Cite