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

Obesity is associated with an increased risk for a wide variety of chronic health conditions. Despite this fact, less than half of obese patients are advised by healthcare professionals to lose weight. Creating a viable plan for losing weight and maintaining weight loss is difficult. Lifestyle change is always the cornerstone of treatment, but two new therapeutic agents approved for long-term use, sibutramine and orlistat, can help maximise success. Increased weight loss can lead to reductions in the risk of obesity-related co-morbidities. Sibutramine and orlistat offer new weight reduction opportunities for obese patients.
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PMID:The new role of pharmacotherapy for weight reduction in obesity. 1246 83

Obesity is a major chronic health problem in adults. It is a complex, multifactorial disorder characterised by excess accumulation of adipose tissue. It is associated with a number of complications including cardiovascular disease, hypertension, type 2 diabetes, dyslipidaemia and cancer. A weight loss in the order of 5-10% is associated with clinically meaningful reductions with respect to all comorbidities. Diet and exercise has been the cornerstone of weight management therapy, but this approach has limitations, especially for weight maintenance. Previous drugs used in obesity had serious side effects including valvular heart disease. However, recent drugs like orlistat and sibutramine have been rigorously tested and proven safe. Orlistat, a lipase inhibitor, inhibits absorption of dietary fat by approximately 30%. Taken with a hypocaloric diet, it produces and maintains clinically meaningful weight loss. Sibutramine is a centrally-acting agent which enhances satiety and thermogenesis by inhibiting serotonin and noradrenaline re-uptake. It is appropriate for patients who are unable to lose weight by lifestyle modification.
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PMID:Pharmacological management of obesity. 1247 68

Obesity and its associated diseases are an increasing challenge in medicine. A change in lifestyle is usually the first step with modifications in nutrition, physical activity and behavior. However, most of obese patients are not able to follow such a treatment regimen for a longer period of time. If they do not lose > 5% of initial weight within 3-6 months, pharmacological intervention should be taken into account. Orlistat, a gastro-intestinal lipase inhibitor, enhances fat excretion thereby reducing energy uptake and body fat. Studies up to 4 years document a net weight loss of 3-5 kg, all cardiovascular risk factors are reduced. Sibutramine, a serotonin- and noradrenalin reuptake inhibitor, promotes satiety and stimulates energy expenditure. Within one year a net weight reduction of 4-6 kg is achieved and morbidity as well as quality of life are improved. For both drugs no end-point outcomes are available so far. The anti-obesity drugs orlistat and sibutramine are useful tools for overweight and obese patients as an adjunct to lifestyle changes. Under the supervision of experienced physicians the combined treatment consisting of non-pharmacological and pharmacological methods reduces body weight in more than half of the patients and improves morbidity and quality of life.
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PMID:[Weight loss via drug therapy]. 1273 23

Sibutramine sensitivity assay in genetically obese (bombesin BB3 receptor (BRS-3)-deficient mice, KK-Ay mice, db/db mice and Zucker obese rat) and wild-type animals was examined. The sensitivity of Sibutramine (10 mg/kg, p.o.) in BRS-3-deficient mice was retained as well as normal animals; however, it was decreased in KK-Ay, db/db mice and Zucker obese rat. The suppression values of food intake in BRS-3-deficient, KK-Ay, db/db mice and Zucker obese rat were 49.8+/-5.8%, 16.1+/-4.7%, 0.1+/-2.8% and -2.0+/-2.2% (mean +/- S.E.), respectively. Next, we found that the contribution of hyperphagia was small in the progress of obesity in BRS-3-deficient mice by calculating energy efficiency. Our results indicate that there is an inverse relationship between the sensitivity to Sibutramine and the contribution of hyperphagia to the progress of obesity in animals.
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PMID:Sibutramine sensitivity assay revealed a unique phenotype of bombesin BB3 receptor-deficient mice. 1287 36

Medications are useful adjuncts to diet and exercise and may help patients lose weight and maintain significant weight loss (5%-10% from baseline). Pharmacologic approaches are indicated in those patients who have had prior weight-loss attempts, who have a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 27 kg/m2 with comorbidity, and who are motivated and ready to undertake dietary and physical activity changes. This article provides a treatment algorithm to help physicians measure meaningful weight loss and proposes conservative blood pressure limits to guide the long-term prescription of sibutramine. Sibutramine can be a useful tool in the obesity treatment toolbox if used by knowledgeable practitioners.
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PMID:Use of sibutramine to treat obesity. 1456 56

Obesity is a multifactorial, chronic disorder that has reached epidemic proportions in most industrialised countries and is threatening to become a global epidemic. Clinical management of obese patients is complex and serious doubts have arisen with regard to safety and efficacy of drug therapy. Following the withdrawal of fenfluramine and dexfenfluramine in 1997, interest has focused on novel anti-obesity drugs. Pharmacological approaches to the management of obesity can, in broad terms, use different distinct strategies: firstly, to reduce energy intake; secondly, to increase energy expenditure; and thirdly, to alter the partitioning of nutrients between fat and lean tissue. Sibutramine is a serotonin-noradrenaline (norepinephrine) reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The pharmacological mechanisms by which sibutramine exerts its weight loss effect are likely due to a combination of reduced appetite, feelings of satiety and possibly the induction of thermogenesis. The efficacy of sibutramine for inducing initial weight loss and the subsequent maintenance of weight loss is well proven in short- and long-term clinical trials of up to 2 years' duration. Most individual placebo-controlled trials and pooled estimates found that the drug produced statistically significant greater weight loss than placebo at all observed endpoints (weighted mean difference for weight change at 8 weeks: -3.4 kg; mean difference range for weight change at 6 months: -4.0 to -9.1 kg; and at 1 year: -4.1 to -4.8 kg). The most frequent dosage regimen in these trials was 10-20 mg daily. Findings suggested a dose-effect relationship in terms of weight loss. Sibutramine was also associated with better weight maintenance relative to placebo (statistically significant difference). Results from mainly small trials showed that sibutramine produced more favourable outcomes in terms of loss of fat mass, reduction in body mass index and loss of > or = 5-10% of initial bodyweight. The most commonly reported adverse effects of sibutramine are headache, constipation and nausea. Certain adverse events associated with the nervous system, including dizziness, dry mouth and insomnia, are reported by > 5% of patients receiving sibutramine. Increases in blood pressure and heart rate were possible adverse effects that require regular monitoring especially in obese hypertensive patients. Neither left-sided cardiac valve disease nor primary pulmonary hypertension was associated with the use of sibutramine. The assessment of the benefit-risk profile of sibutramine remained positive, although the product must be kept under regular review.
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PMID:A benefit-risk assessment of sibutramine in the management of obesity. 1458 64

Sibutramine is a serotonin and norepinephrine reuptake inhibitor, used in the treatment of obesity. In this study, cardiovascular effects of sibutramine (0.9, 3, or 9 mg kg(-1) i.p.) were measured in conscious Sprague-Dawley rats, in the absence and presence of beta- and/or alpha-adrenoceptor antagonism (with propranolol and/or phentolamine, respectively). Sibutramine caused pressor and tachycardic effects, with celiac and mesenteric vasoconstrictions, and hyperemic hindquarters vasodilatation. Pretreatment with propranolol inhibited the tachycardic and hindquarters vasodilator effect of sibutramine, whereas phentolamine inhibited the pressor and vasoconstrictor effects of sibutramine. In the presence of phentolamine, sibutramine caused hyperemic mesenteric vasodilatation. In preconstricted, isolated, mesenteric vessels, sibutramine and its metabolites BTS 54505 (N-desmethylsibutramine) and BTS 54354 (N-didesmethylsibutramine) (10 microM) produced significant vasodilations. Neither sibutramine nor BTS 54505 enhanced vessel sensitivity to norepinephrine, whereas BTS 54 354 produced a significant leftward shift in the concentration-response curve to norepinephrine. Collectively, the results indicate that the overt cardiovascular effects of sibutramine involve alpha-adrenoceptor-mediated celiac and mesenteric vasoconstrictions, and beta-adrenoceptor-mediated hindquarters vasodilatation and tachycardia. The mesenteric vasodilator response to sibutramine, seen in the presence of phentolamine, may be a direct effect of the drug and/or its metabolites, on vessel tone. The cardiovascular effects of sibutramine in vivo may be secondary to inhibition of peripheral and/or central reuptake of monoamines by the metabolites BTS 54354 and/or BTS 54505. It remains to explain why BTS 54354, but not BTS 54505, enhanced norepinephrine sensitivity in vitro, because both metabolites are potent inhibitors of the norepinephrine transporter.
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PMID:Acute cardiovascular effects of sibutramine in conscious rats. 1463 34

In many industrialized nations, obesity is now considered an epidemic, resulting in accelerated morbidity and mortality. Obesity is associated with an increased risk of coronary artery disease as well as the metabolic syndrome comprising abdominal obesity, increased fasting blood glucose levels, dyslipidemia and hypertension, which are all recognized cardiovascular risk factors. Diet, exercise, and lifestyle changes constitute important recommendations for treatment. Unfortunately, although effective in some individuals, these recommendations have proven to be ineffective in adequately addressing the broad, enlarging scope of this public health problem. Drug treatment is often indicated but is somewhat limited by the minimal number of well tolerated drugs that have proven to have long-term efficacy in maintaining bodyweight loss. For example, phentermine may result in modest bodyweight loss through suppression of appetite, but potential cardiovascular adverse effects exist and the efficacy is mainly short-term. Sibutramine, an inhibitor of serotonin and norepinephrine (noradrenaline) reuptake, may increase satiety and result in modest bodyweight loss. However, cardiovascular adverse effects may occur in susceptible patients. Nonetheless, sibutramine is one of the few drugs that has been approved by the US Food and Drug Administration (FDA) for bodyweight loss. Orlistat, a lipase inhibitor, is also approved by the FDA for bodyweight loss but may have bothersome gastrointestinal adverse effects, especially among patients who do not adhere to the recommended low-fat diet. Ongoing studies continue to evaluate other drug treatments that may result in bodyweight reduction through a number of different mechanisms. It is anticipated that the development of effective and well tolerated antiobesity drugs will elevate the pharmacologic treatment of obesity to the status of other cardiovascular risk factors and metabolic disorders. This may be especially important given that dyslipidemia, hypertension and type 2 diabetes mellitus are often secondary to, or exacerbated by, obesity.
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PMID:Pharmacotherapy of obesity: currently marketed and upcoming agents. 1472 70

In order to clarify the mechanism underlying the anti-obesity effects of sibutramine, we examined the effects of sibutramine on extracellular levels of dopamine and 5-hydroxytryptamine (5-HT) through microdialysis in the striatum in unanesthetized and freely moving rats. Sibutramine (5 mg/kg, oral administration (p.o.)) increased extracellular dopamine and 5-HT levels in rat striatum. The tricyclic antidepressant dosulepin (80 mg/kg, p.o. or 1 microM perfusion through the striatal probe) increased 5-HT levels only. Sibutramine-induced dopamine release was antagonized by perfusion of tetrodotoxin (1 microM) through the microdialysis probe in the striatum. However, sibutramine-induced dopamine release was not inhibited by prazosin (1 mg/kg, intraperitoneal injection (i.p.)), a suppressor of serotonergic activity in the striatum via blockade of alpha(1)-adrenoceptors, or perfusion with nomifensine (1 microM), an inhibitor of dopamine re-uptake. These results suggest that sibutramine increases dopamine levels in the striatum by exocytotic release and not by a carrier-mediated mechanism.
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PMID:Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine. 1474 5

Since obesity is a chronic disorder, a long-term approach is essential, and modern obesity pharmacotherapy means medicating as an adjunct to diet and physical activity not only to achieve weight loss, but also to maintain it. Sibutramine is a US Food and Drug Administration- and European Committee for Proprietary Medicinal Products-approved medication with demonstrated efficacy in long-term obesity management. It is a norepinephrine-serotonin reuptake inhibitor and produces weight loss by a dual mechanism: reduction of food intake and increase in energy expenditure. Sibutramine is given once daily in doses ranging from 5-15 mg. The amount of weight lost with sibutramine is related to both the dose of the drug and the intensity of the behavioral therapy component. Sibutramine produces a weight loss from baseline of more than 5% in over 75% of patients who are prescribed 15 mg daily, and it produces weight loss that averages 5-8% from baseline, independently of the behavioral approach. Weight loss with sibutramine is associated with improvement in waist circumference, lipids, glycemic control, uric acid and health-related quality of life. Sibutramine use is associated with small increases in mean resting blood pressure, but the individual response is variable and not all patients will have blood pressure increases. The drug is also associated with small increases in mean heart rate and should therefore not be used in patients with a history of cardiac arrhythmia. Because it is a serotonin and norepinephrine reuptake inhibitor, sibutramine should not be used with monoamine oxidase inhibitors or noradrenergic agents, and caution is advised in prescribing sibutramine to patients on selective serotonin reuptake inhibitor antidepressants. Given the growing appreciation for the health benefits that can be achieved with even a relatively small weight loss, physicians must become adept in office approaches to achieve modest weight loss. Sibutramine is a useful adjunct to diet and physical activity approaches and can help selected patients achieve and maintain weight loss with concomitant health benefits.
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PMID:Clinical use of sibutramine. 1498 69


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