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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although comprehensive obesity treatment programmes were shown to induce weight loss and to improve risk factors and comorbidities, the weight reduction is moderate and most patients will rapidly regain weight. For these reasons, drugs have been developed or are in development to support and maintain weight loss. At present, two drugs are available for the adjunct treatment of obesity. Sibutramine is a centrally acting inhibitor of noradrenaline and serotonine reuptake, thereby decreasing caloric intake and increasing energy expenditure. Orlistat is a specific lipase inhibitor that impairs fat absorption, thereby reducing fat uptake. Both drugs have been found to be effective and safe in a number of clinical studies for up to two years. The current experience with these drugs raises questions related to the long-term efficacy with particular reference to cardiovascular end-points. In addition, other current and future pharmacological principles for weight reduction are discussed. There is no doubt that an evidence-based rational pharmacological treatment of obesity is still in an early stage.
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PMID:Current pharmacological approaches to the treatment of obesity. 1146 1

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight. Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is also contraindicated in patients with cardiovascular disease. Orlistat is not systemically absorbed; therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.
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PMID:Pharmacologic options for the treatment of obesity. 1147 77

Obesity is a chronic disease and requires ongoing treatment. Type 2 diabetes is associated with obesity and improves with weight loss. Diets of 800 kcal/d induce twice the weight loss induced by weight loss medications. The strength of weight loss medication, which should be used with diet and a lifestyle change program, is the maintenance of weight loss. Sibutramine and orlistat are the only two medications approved for the long-term treatment of obesity. Orlistat gives a reduction of low-density lipoprotein (LDL) cholesterol in excess of that expected with weight loss, and the drop in blood pressure expected with weight loss is not seen with sibutramine. Except in newly diagnosed patients with diabetes subjects, patients with diabetes lose half the weight of subjects who do not have diabetes when treated with weight loss medications. Metformin and, to a lesser extent, acarbose cause weight loss, making them attractive choices for the treatment of obese type 2 diabetic subjects. Repaglinide appears to be weight-neutral, but other medications for patients with diabetes can be associated with weight gain. Many new medications are in development for the treatment of obesity. These new medications act through a variety of mechanisms and will surely play an increasingly important role in the treatment of obese patients with type 2 diabetes.
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PMID:Obesity medications and the treatment of type 2 diabetes. 1147 74

The regulation of energy balance is enormously complex, with numerous genetic, hormonal, neural and behavioral, and societal influences. Although the current epidemic of obesity clearly has its underpinnings in the changes in culture during the past half-century (see other articles in this issue), the role of the neuroendocrine system in the genesis of obesity, as described in this article, is physiologically and therapeutically unavoidable. An understanding of this system has suggested organic causes (and therapies) for some rare and not-so-rare forms of obesity. With so many inputs, it is not far-fetched to assume that dysfunction of other parts of this feedback system will be found to explain other forms of obesity in the future. What does this mean for obese children entering the pediatrician's office? Fortunately or unfortunately, diet and exercise are the mainstays of obesity therapy for children and adults. Most diet-exercise programs result in an acute 11-kg weight loss in adults; the question is whether it can be sustained without significant long-term behavioral modification. For instance, the European Sibutramine Trial of Obesity Reduction and Maintenance trial showed that 42% of treated subjects drop out; of those remaining, 77% of subjects lost more than 5% of initial body weight, but only 43% of those maintained more than 80% of this over 2 years. Could there be an organic component in those who do not respond? Of course, obesity pharmacotherapies sometimes have beneficial acute effects, but these drugs work for only as long as they are consumed; discontinuation tends to result in a "rebound" weight gain, suggesting that the cause of the obesity is still present. Furthermore, in 2001, there are no obesity drugs approved for children. A useful guiding principle is that children deserve at the minimum an initial medical evaluation, including birth weight, medical history, family history, dietary evaluation, and exercise assessment. Perhaps the most important feature that can distinguish "organic" from "behavioral" weight gain in childhood is the age of the "adiposity rebound." The Centers for Disease Control and Prevention now supplies BMI charts for boys and girls at www.cdc.gov/growthcharts. Plotting of the BMI versus age allows pediatricians to determine the age at which the BMI starts to increase (mean, 5.5 years). The earlier the adiposity rebound, the more likely the child will be obese as an adult, and the more likely that an organic cause can be determined. In such patients, thyroid levels and fasting insulin and leptin levels should be measured. An initial attempt at diet and exercise is essential; patients who do not respond with BMI stabilization should be investigated for a more ominous cause of their obesity. As the nosology of obesity improves, pediatricians will be able to increase the diagnostic efficiency and therapeutic success of this unfortunate, debilitating, and expensive epidemic.
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PMID:The neuroendocrinology of childhood obesity. 1149 43

The regulation of energy balance is enormously complex, with numerous genetic, hormonal, neural/behavioral, and societal influences. Although the current epidemic of obesity has its underpinnings in the changes in culture during the last half century, the role of the neuroendocrine system in the genesis of obesity is physiologically and therapeutically unavoidable. Increased understanding of this system has suggested organic etiologies (and therapies) for some rare and not-so-rare forms of obesity. With so many inputs, it is not implausible that dysfunction of other parts of this feedback system will be found to explain other forms of obesity in the future. Fortunately or unfortunately, diet and exercise remain the mainstays of obesity therapy. Most diet-exercise programs result in an acute 11-kg weight loss in adults; the question is whether it can be sustained without significant long-term behavior modification. In the European Sibutramine Trial of Obesity Reduction and Maintenance (STORM), 42% of treated patients dropped out; of those remaining, 77% of subjects lost more than 5% of initial body weight, but only 43% of these individuals maintained greater than 80% of this loss over 2 years. Could there be an organic component in persons who do not respond? Obesity pharmacotherapies sometimes have beneficial acute effects, but these effects are impermanent; discontinuation tends to result in a rebound weight gain, suggesting that the etiology of the obesity is still present. A useful guiding principle is that patients who do not respond to diet and exercise should undergo an initial medical evaluation, including assessments of birth weight, past medical history, weight history, family history, diet, exercise, and fasting insulin and thyroid levels. As the nosology of obesity improves, diagnostic efficiency and therapeutic success should increase, leading to a decrease in associated morbidity, mortality, and socioeconomic ramifications.
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PMID:The neuroendocrinology of obesity. 1157 40

Every third German needs to lose weight for health reasons. Risk assessment of obesity is based on the BMI, the distribution pattern of body fat, and the presence of concomitant diseases and sequelae of obesity. The most important prerequisites are personal motivation and the ability of the patient to self-manage his/her problem. The basic long-term weight-reduction program includes a low-calory diet, increased physical activity, and specific measures aimed at modifying eating habits. Should the basic programs fail to produce the necessary results, the two weight-reducing drugs Sibutramine and Orlistat are available--with appropriate consideration being given to contraindications. Surgical measures, such as gastric banding and gastroplasty are reserved for patients that prove resistant to conservative measures.
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PMID:[Therapy of obesity. Setting realistic goals]. 1169 84

The prevalence of hypertension among the obese is twice as high as that in persons of normal weight. Not only the BMI, but, and in particular, the circumference of the waist correlates with blood pressure. A relationship also obtains between BMI and left-ventricular muscle mass, with left-ventricular hypertrophy occurring twelve times more often among the obese than among slim persons. Obesity puts a strain on both the hemodynamics and metabolism of the heart. On the one hand, long-term sequelae include disordered cardiac function extending to cardiomyopathy, on the other, obesity is responsible for sympatho-adrenergic stimulation considered to be a cause of insulin resistance, and is thus, in particular in the hypertensive, closely associated with metabolic syndrome. Specific nondrug treatment options include weight reduction, a low-salt diet and physical exercise. In some cases, Sibutramine and Orlistat may have a supporting role. For the antihypertensive treatment of the obese, drugs with a favorable hemodynamic and metabolic effect should be used.
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PMID:[Hypertension and cardiomyopathy in obesity. Treat the heart simultaneously]. 1169 85

Sibutramine (Reductil, Abbott-Knoll, 10 mg and 15 mg) is a new appetite regulator recommended in the treatment of obesity. It is a noradrenaline and 5-hydroxytryptamine reuptake inhibitor which exerts its effects in vivo predominantly via its secondary and primary amine metabolites. Sibutramine is indicated as an adjunctive therapy within a weight management programme in patients with obesity (BMI > or = 30 kg/m2) or in overweight subjects (BMI > or = 27 kg/m2) if other eight-related risk factors are present (dyslipidaemias, diabetes mellitus). In those patients with an inadequate response on initial dose of 10 mg per day (suggested as less than 2 kg weight loss in four weeks), the dose may be increased to 15 mg once daily, providing that sibutramine is well tolerated. Several large-scale randomized clinical trials demonstrated the efficacy of long-term (at least one year) treatment with sibutramine in obese subjects with or without type 2 diabetes. Sibutramine was also shown to help in maintaining long-term weight reduction. Most frequent side-effects are dry mouth and constipation, as well as mild increase in heart rate and arterial blood pressure. The impact of sibutramine on cardiovascular morbidity and mortality of obese nondiabetic and diabetic patients will be studied soon in a large international prospective clinical trial.
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PMID:[Pharma-clinics. Medication of the month. Sibutramine (Reductil)]. 1170 9

At present only two drugs are approved for long-term treatment of obesity. Sibutramine inhibits the reuptake of serotonin and norepinephrine. In clinical trials it produces a dose-dependent 5-10% decrease in body weight. Its side effects include dry mouth, insomnia, asthenia, and constipation. In addition, sibutramine produces a small increase in blood pressure and pulse that is a contraindication to the use of this drug in some individuals with heart disease. Xenical is the other drug approved for long-term use in the treatment of obesity. It works by blocking lipase and thus increasing the fecal loss of triglyceride. One valuable consequence of this mechanism of action is the reduction of serum cholesterol that averages about 5% more than can be accounted for by weight loss alone. In clinical trials it produces a 5-10% loss of weight. Its side effects are entirely due to undigested fat in the intestine that can lead to increased frequency and change in the character of stools. It can also lower fat-soluble vitamins. The ingestion of a vitamin supplement before bedtime is a reasonable treatment strategy. The effect on weight loss during long-term trials with these two drugs is shown in Figs 7 and 8 above. Also in this figure is data on phentermine used in trials of six months or more. Although there were differences in mean weight losses with these drugs, when the placebo effect was taken into account they all had a surprisingly similar magnitude of weight loss.
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PMID:Drug treatment of obesity. 1172 27

Catecholamine, dopamine, serotonine (5HT) and neuronal histamine are anorectic monoamines and act as anorectic neurotransmitters. The anorectic agents as modulators of these monoamines inhibit appetite by activating release together with suppressing reuptake of those monoamines. The anorectic agents were classified in clinical use into either alpha 1, beta-adrenergic receptor agonists or 5HT-receptor agonist. Dexfenfluramine, a 5HT-receptor agonist, was inhibited in clinical use because of its cardiac complications including pulmonary hypertension and valvelar disease. Mazindol is an adrenergic agonist and the solitary anti-obesity drug used clinically in Japan. Sibutramine shows the effects of both beta-adrenergic and serotonergic receptor agonists. Sibutramine induces not only appetite suppression but also acceleration of peripheral energy expenditure. No histaminergic anorectics have been employed in the clinical situation to date. L-Histizine, precursor amino acid of endogenous neuronal histamine, is useful for suppression of food intake, lipolytic acceleration of peripheral adipose tissues and enhanced energy expenditure in both animals and humans. L-Histizine thus inspires development of more effective and safer anorectics that can be used without suffering from the rebound phenomenon of body weight.
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PMID:[Monoaminergic anorectic agents]. 1172 32


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