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1.
Orv Hetil ; 153(10): 363-73, 2012 Mar 11.
Artigo em Húngaro | MEDLINE | ID: mdl-22370224

RESUMO

Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Amidas/uso terapêutico , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/farmacologia , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Metabolismo Basal/efeitos dos fármacos , Benzazepinas/uso terapêutico , Benzoxazinas/uso terapêutico , Índice de Massa Corporal , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Fator Neurotrófico Ciliar/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclobutanos/uso terapêutico , Dexfenfluramina/uso terapêutico , Ácidos Graxos/uso terapêutico , Feminino , Fenfluramina/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Absorção Intestinal/efeitos dos fármacos , Lactonas/uso terapêutico , Leptina/uso terapêutico , Estilo de Vida , Liraglutida , Masculino , Norepinefrina/análogos & derivados , Obesidade/prevenção & controle , Obesidade/terapia , Obesidade Mórbida/tratamento farmacológico , Orlistate , Piperidinas/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptor Tipo 4 de Melanocortina/antagonistas & inibidores , Rimonabanto , Saciação/efeitos dos fármacos , Serotonina/análogos & derivados , Proteínas de Transporte de Sódio-Glucose/antagonistas & inibidores , Sacarose/análogos & derivados , Sacarose/uso terapêutico , Hormônios Tireóideos/uso terapêutico
3.
Neuropsychopharmacology ; 36(2): 423-33, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20927048

RESUMO

The now-banned anorectic molecule, dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT(2B) receptors have important roles in dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT(2B) receptors in dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to dexfenfluramine (3-10 mg/kg) observed in wild-type mice (1-4 h) was eliminated in mice lacking 5-HT(2B) receptors (5-HT(2B)(-/-)). These findings were further validated by the lack of hypophagic response to dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22 ± 0.24). Using microdialysis, we observed that in 5-HT(2B)(-/-) awake mice, the dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT(2B) receptors. These findings strongly suggest that activation of presynaptic 5-HT(2B) receptors is a limiting step in the serotonin transporter dependent-releasing effect of dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior.


Assuntos
Depressores do Apetite/farmacologia , Regulação do Apetite/efeitos dos fármacos , Dexfenfluramina/farmacologia , Obesidade/tratamento farmacológico , Receptor 5-HT2B de Serotonina/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Depressores do Apetite/uso terapêutico , Regulação do Apetite/fisiologia , Dexfenfluramina/uso terapêutico , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Receptor 5-HT2B de Serotonina/deficiência , Receptor 5-HT2B de Serotonina/genética , Serotonina/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
5.
Actas esp. psiquiatr ; 36(4): 218-222, jul.-ago. 2008. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-66883

RESUMO

Introducción. Las pruebas de estimulación de prolactina con agonistas serotoninérgicos han sido ampliamente utilizadas en el estudio de diversas patologías psiquiátricas; sin embargo, la caracterización de su respuesta en sujetos normales es aún incompleta. Objetivo. Comparar la respuesta a la estimulación serotoninérgica utilizando dexfenfluramina, un agente serotoninérgico específico, en hombres y mujeres jóvenes sanos, controlando el ciclo menstrual en estas últimas. Métodos. Se estudió a 10 mujeres y 9 hombres, a quienes se les administró 30 mg de dexfenfluramina por vía oral, midiendo los niveles de prolactina cada hora por un período de5 h. El nivel basal, el nivel máximo y la variación de prolactina fueron comparados en ambos grupos. Resultados. En los grupos etarios estudiados (edad promedio para los hombres: 19,9±2,5 años; edad promedio paral as mujeres: 20±1,5 años), el nivel máximo de prolactina y la respuesta a prolactina (Δ PRL) fueron significativamente mayores en mujeres (valor p: 0,02 y 0,04, respectivamente). Conclusiones. Las mujeres jóvenes sanas muestran una mayor respuesta a la estimulación con dexfenfluramina que los hombres jóvenes sanos. Las implicancias clínicas y biológicas de esta observación se discuten en el contexto de la literatura (AU)


Introduction. Prolactin stimulation test with serotonergic stimulants has been widely used in the study of diverse psychiatric disorders. However, the characterization of this response in normal subjects is still in complete. Objective. To compare the response to serotonin stimulation using dexfenfluramine, a specific serotonergic agent, in young healthy men and women, controlling the menstrual cycle. Methods. A total of 10 women and 9 men, who were given 30 mg of dexfenfluramine orally, were studied and their levels of prolactin were measured on an hourly basis for a five-hour period. Baseline, maximum and delta values of prolactin were compared for both groups. Results. According to the age groups studied (mean age for men: 19.9±2.5 years old; mean age for women: 20±1.5 years old), the prolactin maximum level and the response to prolactin (ΔPRL) were significantly higher in women (p-values: 0.02 and 0.04, respectively). Conclusions. Young healthy women show a greater response to stimulation with dexfenfluramine than young healthy men. Clinical and biological implications of this observation are discussed in the context of the currently available research papers (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Identidade de Gênero , Dexfenfluramina/uso terapêutico , Inquéritos e Questionários , Ablação por Cateter/métodos , Antagonistas da Serotonina/análise , Antagonistas da Serotonina/síntese química , Antagonistas da Serotonina , Prolactina/agonistas , Prolactina/análise , Inibidores de Captação de Serotonina , Antagonistas de Estrogênios/análise , Moduladores de Receptor Estrogênico
6.
Eur Neuropsychopharmacol ; 18(11): 794-802, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18573641

RESUMO

Excessive consumption of highly palatable foods may contribute to the development of weight gain. Therefore medications that selectively suppress eating of such foods would be useful in clinical practice. We compared the effects of the glutamatergic antagonists memantine and MTEP to dexfenfluramine in baboons given periodic access to highly palatable food and ad libitum access to a standard chow diet. Three days a week baboons received a sugar-coated candy during the first meal and standard standard-diet chow pellets were available in subsequent meals. All baboons derived a greater amount of energy from the single single-candy meal than from the standard diet across an entire day. Pre-treatment with dexfenfluramine, memantine, and MTEP produced decreases in candy consumption without altering candy-seeking behaviour. At the same time, dexfenfluramine and memantine, but not MTEP, produced a decrease in seeking and consumption of standard chow pellets. Both memantine and MTEP are promising agents for the treatment of obesity.


Assuntos
Bulimia Nervosa/tratamento farmacológico , Bulimia Nervosa/psicologia , Ingestão de Alimentos/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Apetite/efeitos dos fármacos , Doces , Condicionamento Operante/efeitos dos fármacos , Comportamento Consumatório/efeitos dos fármacos , Dexfenfluramina/farmacologia , Dexfenfluramina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Masculino , Memantina/farmacologia , Memantina/uso terapêutico , Papio cynocephalus , Piridinas/farmacologia , Piridinas/uso terapêutico , Receptor de Glutamato Metabotrópico 5 , Esquema de Reforço , Agonistas do Receptor de Serotonina/farmacologia , Agonistas do Receptor de Serotonina/uso terapêutico , Caracteres Sexuais , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Ganho de Peso/efeitos dos fármacos
9.
Eur J Pharmacol ; 513(3): 243-8, 2005 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-15862807

RESUMO

We studied the combination of oleoyl-estrone with either dexfenfluramine, sibutramine or phentermine in overweight male rats treated for 10 days in order to determine whether they shared a mechanism of action. Oleoyl-estrone, dexfenfluramine and sibutramine decreased body weight and energy (essentially lipids); losses were higher when combined with oleoyl-estrone. Glycemia was maintained except under phentermine; oleoyl-estrone induced decreases in triacylglycerols, cholesterol, insulin and HOMA (homeostasis model assessment). Combination of oleoyl-estrone and sibutramine resulted in the loss of up to 29% body energy in 10 days. Energy expenditure was maintained. The effects of oleoyl-estrone and dexfenfluramine or sibutramine on appetite were substantially additive. All oleoyl-estrone-treated rats showed increased insulin sensitivity. In conclusion, combined treatment of overweight rats with oleoyl-estrone and sibutramine or dexfenfluramine results in a dramatic loss of weight and fat, whilst maintaining circulating energy homoeostasis.


Assuntos
Fármacos Antiobesidade/farmacologia , Ciclobutanos/farmacologia , Dexfenfluramina/farmacologia , Estrona/análogos & derivados , Obesidade/fisiopatologia , Ácidos Oleicos/farmacologia , Fentermina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Ciclobutanos/uso terapêutico , Dexfenfluramina/uso terapêutico , Interações Medicamentosas , Quimioterapia Combinada , Metabolismo Energético , Estrona/farmacologia , Estrona/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Masculino , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ácidos Oleicos/uso terapêutico , Fentermina/uso terapêutico , Ratos , Ratos Wistar
10.
Prev Med ; 39(6): 1243-8, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15539063

RESUMO

BACKGROUND: Despite the popularity of antiobesity medications, there is a lack of population-based data on their use. In addition, response (termination of pill use and receipt of an echocardiogram) to the fenfluramine and dexfenfluramine market withdrawal among the public has not been described. Lessons learned from this event have implications for future withdrawals. METHODS: We used data from the Behavioral Risk Factor Surveillance System (BRFSS) a random-digit telephone survey. In 1998, six states included detailed questions about the use of prescription weight loss pills in the previous 2 years, n = 16,460 noninstitutionalized adults aged 18 years or older. RESULTS: Almost one third of prescription weight loss pills users were not obese before taking pills. Family and friends and other nonphysicians were reported as sources of medication by one in ten users. One third of users also reported taking nonprescription diet products. Among fenfluramine or dexfenfluramine users, one third continued pill use after the market withdrawal and only one quarter received echocardiograms. CONCLUSIONS: Despite enormous publicity, many persons continued to use fen-phen after the market withdrawal and most did not receive follow-up echocardiograms. Our study raises issues regarding the effectiveness of withdrawal warnings in a small but significant subset. Additional means of communicating risk to individuals are needed for future product withdrawals including special strategies for those lacking healthcare coverage.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Obesidade/tratamento farmacológico , Adulto , Fármacos Antiobesidade/uso terapêutico , Índice de Massa Corporal , Dexfenfluramina/efeitos adversos , Dexfenfluramina/uso terapêutico , Feminino , Fenfluramina/efeitos adversos , Fenfluramina/uso terapêutico , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Vigilância de Produtos Comercializados/estatística & dados numéricos , Serotoninérgicos/efeitos adversos , Serotoninérgicos/uso terapêutico , Fatores Socioeconômicos , Inquéritos e Questionários , Estados Unidos/epidemiologia , Perda de Peso/efeitos dos fármacos
12.
Minerva Pediatr ; 55(5): 471-82, 2003 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-14608270

RESUMO

This article provides current guidelines on the treatment and prevention of childhood obesity. Since factors involved in obesity change with age, the therapeutic approach in pre-school children will be different from pupils and adolescents. The treatment will also be modulated on the basis of weight excess, weight gain velocity and complications. The main goal of the treatment should be to encourage the child and his family to have healthy lifestyle. Families who are not ready for change might benefit from counselling to improve motivation before starting treatment. A detailed alimentary and behavioural history is the start point of the treatment. The strategy of the intervention is to induce changes at three levels: 1) attitudes of parents; 2) physical activity; 3) energy intake. The treatment of the adolescents should take into account the pubertal changes and the psychological aspects of this peculiar period of life. Obesity is a chronic disease and its treatment needs long-life follow-up. The long-term results of the obesity treatment are often disappointing and we have to consider consistent prevention programs for better results.


Assuntos
Obesidade/terapia , Adolescente , Adulto , Fatores Etários , Depressores do Apetite/uso terapêutico , Terapia Comportamental , Índice de Massa Corporal , Criança , Pré-Escolar , Aconselhamento , Dexfenfluramina/uso terapêutico , Dieta , Ingestão de Energia , Exercício Físico , Família , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Estilo de Vida , Masculino , Motivação , Obesidade/tratamento farmacológico , Obesidade/prevenção & controle , Obesidade/cirurgia , Gravidez , Complicações na Gravidez/terapia , Puberdade , Agonistas do Receptor de Serotonina/uso terapêutico , Fatores Sexuais
13.
Curr Womens Health Rep ; 3(2): 116-25, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12628081

RESUMO

Obesity is a chronic disorder that is associated with significant co-morbidity and early mortality. Since the 1970s, amphetamines and amphetamine analogs have been trialed for weight loss. In 1997, the anorexigen agents, fenfluramine (Pondimin; AH Robins, Richmond, VA) and dexfenfluramine (Redux; Wyeth-Ayerst, Philadelphia, PA) gained worldwide attention when reports of associated cardiac valvulopathy and pulmonary hypertension emerged. A landmark report from the Mayo Clinic describing valvular heart disease (VHD) among women exposed to the anorexigen agent combination phentermine-fenfluramine ignited widespread concern, and the products were voluntarily withdrawn from the market by the manufacturers. Currently, the causal relationship between anorexigen agent use and valvulopathy has been validated, yet the extent and complexity of this important clinical issue remains ill-defined.


Assuntos
Depressores do Apetite/efeitos adversos , Doenças das Valvas Cardíacas/induzido quimicamente , Adulto , Depressores do Apetite/uso terapêutico , Dexfenfluramina/efeitos adversos , Dexfenfluramina/uso terapêutico , Ecocardiografia , Feminino , Fenfluramina/efeitos adversos , Fenfluramina/uso terapêutico , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Fentermina/efeitos adversos , Fentermina/uso terapêutico , Agonistas do Receptor de Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/uso terapêutico
17.
Alcohol Clin Exp Res ; 24(10): 1534-41, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11045862

RESUMO

BACKGROUND: A substantial body of evidence supports a role for serotonin in modulating alcohol intake, which suggests that this neurotransmitter represents a promising target for pharmacotherapy development for alcohol use disorders. Dexfenfluramine. a serotonin releaser and reuptake inhibitor, decreases alcohol self-administration by rats. Its greater potency and several mechanisms of action suggest it should be more effective in treating alcohol dependence than drugs that only inhibit serotonin reuptake. METHODS: We conducted an 11 week, randomized, double-blind trial that compared oral placebo and dexfenfluramine 7.5, 15, 22.5, and 30 mg bid in 136 alcohol-dependent patients. A brief behavioral intervention was offered concurrently. RESULTS: The majority of subjects were male (72%), and the age of the group was 44 +/- 1 years (mean +/- SD). Both placebo- and drug-treated groups significantly reduced alcohol consumption compared with baseline (a 55% decrease in mean drinks per day; p < 0.01), but there were no significant differences between drug and placebo groups or dose effects for most outcome measures. CONCLUSIONS: Our results with dexfenfluramine are further evidence that serotonergic medications on their own do not significantly reduce alcohol consumption in alcohol-dependent individuals. Combination pharmacotherapy with agents that act on different receptors or neurotransmitter systems (e.g., naltrexone plus dexfenfluramine) may be one way to enhance serotonergic effects on drinking behavior and should be considered in future medication development clinical trials.


Assuntos
Alcoolismo/tratamento farmacológico , Dexfenfluramina/uso terapêutico , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Dexfenfluramina/administração & dosagem , Dexfenfluramina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Placebos , Caracteres Sexuais
18.
Methods Find Exp Clin Pharmacol ; 22(5): 285-90, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11031729

RESUMO

A meta-analysis was conducted to estimate the difference of weight loss among patients treated with placebo and with fenfluramine or dexfenfluramine after 1, 2, 3, 6, and 12 months of treatment. Placebo-controlled, double-blind, randomized clinical trials, whose results were presented as weight loss by the placebo group and the drug-treated patient group, were selected for the analysis. For the pooled estimations, the method of the weighted means by the inverse of the variance was used. The association between the difference of means and several predictive variables was studied by means of weighted linear regression. Patients treated with fenfluramine or dexfenfluramine achieved a higher weight loss than those receiving placebo in all the periods studied. The greatest efficacy was observed after 3 months of treatment. Beyond this time, there is a decline in the effectiveness. Based on the efficacy data, treatments longer than 3 months would not be justified.


Assuntos
Depressores do Apetite/uso terapêutico , Dexfenfluramina/uso terapêutico , Fenfluramina/uso terapêutico , Obesidade/tratamento farmacológico , Método Duplo-Cego , Humanos , MEDLINE , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Fatores de Tempo
19.
Int J Obes Relat Metab Disord ; 24(6): 735-41, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10878680

RESUMO

BACKGROUND: Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/l and activation at 330 pmol/l instead of activation and inhibition as in controls. OBJECTIVE: To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity. METHODS: Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D-21-D0), participants received a placebo, and in the second (D0-D21), dexfenfluramine (30 mg/day). At D-21, D0 and D21 participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/l insulin. At D2, basal PDH activity and clinical parameters were assayed. RESULTS: In both groups of participants at D0 all parameters tested were constant with respect to D-21; at D2, only basal PDH activity rose significantly; at D21, basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, FI, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants. CONCLUSION: In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating lymphocytes, of PDH derangements described as reflecting a disorder underlying insulin resistance.


Assuntos
Dexfenfluramina/uso terapêutico , Resistência à Insulina , Obesidade/tratamento farmacológico , Complexo Piruvato Desidrogenase/sangue , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Insulina/sangue , Insulina/farmacologia , Linfócitos/enzimologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Placebos , Perda de Peso
20.
Diabetes Metab Res Rev ; 16(2): 114-24, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10751751

RESUMO

Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction should be considered as a key objective. In this respect, several antiobesity drugs have demonstrated potential. However, while fenfluramine and dexfenfluramine have been shown to promote weight loss and to directly improve insulin sensitivity, being two mechanisms contributing to better blood glucose control in obese Type 2 diabetic patients, they were recently withdrawn due to safety problems. Sibutramine, a new selective norepinephrine and serotonin reuptake inhibitor, promotes weight loss by decreasing food intake, an effect which leads to a mild improvement (significant in patients losing > or =5% of initial body weight) of blood glucose control in obese diabetic patients. Similarly, orlistat, a selective gastrointestinal lipase inhibitor which increases faecal fat losses, enhances diet-induced weight reduction and improves both blood glucose control and vascular risk profile, especially dyslipidaemia, in obese Type 2 diabetic patients. Further studies are required to better identify good responders to pharmacotherapy and specify the role of antiobesity agents in the overall long-term management of obese subjects with Type 2 diabetes. Other novel pharmacological approaches deserve further consideration, for instance beta-3 agonists aiming to increase energy expenditure, drugs interfering with tumor necrosis factor-alpha (TNF-alpha) or free fatty acid release by the adipose tissue or agents that slow gastric emptying. However, until now, results regarding efficacy and/or safety have been disappointing or preliminary in humans.


Assuntos
Depressores do Apetite/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/prevenção & controle , Obesidade , Glicemia/metabolismo , Dexfenfluramina/uso terapêutico , Diabetes Mellitus Tipo 2/fisiopatologia , Ingestão de Energia , Fenfluramina/uso terapêutico , Humanos , Serotoninérgicos/uso terapêutico
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