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

(1) The reference treatment for achieving weight loss by obese patients is a combination of dietary measures, exercise and behavioural interventions. There is currently no drug treatment with demonstrated efficacy on the morbidity or mortality associated with excess body weight. (2) Sibutramine, a serotonin- and noradrenaline-reuptake inhibitor structurally related to the amphetamines has been granted marketing authorisation in France for the treatment of obesity and excess body weight in patients with associated risk factors. (3) The clinical file on sibutramine contains no trial focusing on morbidity or mortality end points. (4) According to comparative clinical trials, weight loss during a 6-12 month course of sibutramine is, on average, between 3 and 9 kg greater than that on placebo. Patients regain weight after sibutramine cessation. (5) Sibutramine has little or no benefit on blood sugar or lipid parameters. (6) The main known adverse effect of sibutramine is increased blood pressure. Sibutramine also has amphetamine-like side effects. (7) In practice, sibutramine currently has no place in the management of obesity.
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PMID:Sibutramine: new preparation. Slight weight loss; but also a slight rise in blood pressure ... 1182 28

Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.
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PMID:Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. 1184 Feb 24

Sibutramine is the first of a new generation of weight management drugs, and offers long-term control of weight when used as an adjunct to diet and exercise. This paper considers the criteria set down by the European Union's regulatory agency for its use and how this relates to the information now available on its efficacy, side-effect profile and benefits in different patient groups. The data presented relate to 18-65y olds; its use in other age groups has not been established. The EU licence permits continuous treatment for periods of up to 1 y; the STORM study has now led the US Food and Drug Administration to extend clearance to 2 y. The addition of sibutramine to a regimen of diet, exercise and lifestyle modification results in 3-5 times more patients responding to a weight-reduction programme, ie achieving more than 5% weight maintenance. Sibutramine is indicated for use in obese patients (BMI > 30 kg/m2) and also overweight patients with a BMI > 27 kg/m2 who have additional obesity-related risk factors such as type 2 diabetes or dyslipidaemia.
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PMID:When, for whom and how to use sibutramine? 1191 1

Obesity and hypertension are closely associated risk factors for cardiovascular disease. An increase in body mass index is commonly associated with an increase in blood pressure and weight reduction is recommended as the principal intervention in the obese hypertensive patient. Sibutramine therapy, as part of a programme of diet and exercise, can help achieve marked weight reduction and improve metabolic and other cardiovascular risk factors. In hypertensive patients, weight loss induced by sibutramine has also been found to reduce blood pressure. Studies have shown that in the obese, well-controlled hypertensive patient, sibutramine is a safe and well-tolerated therapy offering the many clinical benefits associated with weight reduction in this high-risk population.
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PMID:Sibutramine in overweight/obese hypertensive patients. 1191 2

Sibutramine offers three types of benefit in weight management: by enhancing weight loss, by improving weight maintenance and by reducing the comorbidities of obesity. The clinical effects of sibutramine are explained through its known mode of action as a serotonin (5-HT) and noradrenaline reuptake inhibitor (SNRI). This dual mechanism of action results in two synergistic physiological effects--a reduction in energy intake and an increase in energy expenditure, which combine to promote and maintain weight loss.
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PMID:How does sibutramine work? 1191 6

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. Though sibutramine was originally evaluated for possible use as an antidepressant, its research development was eventually redirected to evaluate it as an anorexiant. 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. Its efficacy for inducing an initial weight-loss and the subsequent maintenance of the weight-loss is well proven in short- and long-term clinical trials of up to 2 years duration. In general, sibutramine has been well tolerated. Increases in blood pressure and heart rate are possible adverse effects that require regular monitoring. Sibutramine is one of the few established and well-proven agents for obesity available for use today and should be considered effective in the management of patients requiring pharmacotherapy as part of the multi-modal approach to weight-loss.
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PMID:The discovery and status of sibutramine as an anti-obesity drug. 1200 30

Sibutramine is a combined serotonin(5-HT) and noradrenaline (NA)re-uptake inhibitor. Sibutramine works predominantly through its two pharmacologically active metabolites (i.e. primary and secondary amines) which induce marked weight loss by affecting both food intake and energy expenditure. It is able to enhance the physiological process of satiety, and to stimulate thermogenesis, increasing the efferent sympathetic activity to thermogenically active brown fat. There is a dose-related reduction in body weight in clinical trials with sibutramine, with weight loss up to 11% below baseline, which can last up to 18 months with continued treatment. When weight loss is induced with a very low calorie diet (VLCDL), patients randomized to the sibutramine treatment continued to lose weight over a 1 year period, reaching 15% below baseline, whereas the placebo-treated patients regained some weight. Sibutramine improves metabolic fitness, by decreasing the biochemical risk factors associated with obesity, such as plasma triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol, glucose and insulin, and increasing HDL-cholesterol. In controlled studies, 84% of sibutramine-treated patients reported side effects, most commonly including dry mouth, constipation and insomnia, compared with 71% of patients receiving placebo. A small increase in heart rate and blood pressure also occurs and persists for as long as treatment is continued, which, therefore, requires monitoring. Nevertheless, successful treatment of moderately hypertensive obese patients with sibutramine has been demonstrated without undue blood pressure problems and even a mean lowering of blood pressure associated with weight loss. Finally, sibutramine does not have the potential for abuse that is characteristic of amphetamine and it is indistinguishable from placebo in abuse potential studies.
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PMID:An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action. 1211 86

Obesity is a general medical condition associated with an increase in morbidity and mortality. Although it would be desirable to use efficacious prevention programs, the success rates reported to date have been rather disappointing. In this observational study, a new drug treatment regimen was evaluated in five obese patients with a mean age of 39.6 +/- 4.2 years and an initial body mass index between 34.5 and 38.3 kg/m for a period of 96 weeks. The patients showed restrained and unrestrained eating patterns according to a German version of the Three-Factor Eating Questionnaire and were treated in an add-on regimen with the combination of three drugs with different anorectic properties that were consecutively introduced in an interval of 16 weeks. First, orlistat (120 mg three times a day) was given as a monotherapy. Sibutramine (15 mg in the morning) and then topiramate (in a dose dependent on appetite suppression and side effects) were added for a total duration of 48 weeks. A 48-week maintenance and relapse prevention treatment period with topiramate monotherapy followed the discontinuation of orlistat and sibutramine. This outpatient treatment procedure was tolerated well, although side effects occurred in all patients depending on the phase of the treatment regimen. After 96 weeks, the mean body mass index was 25.7 +/- 1.2 kg/m. Moreover, a normalization of eating patterns according to the Three-Factor Eating Questionnaire could be noticed. Factor 3, hunger, was significantly reduced. This treatment plan may be highly effective and safe in a subpopulation of obese patients.
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PMID:Add-on combination and maintenance treatment: case series of five obese patients with different eating behavior. 1235 78

Sibutramine has a dual mode of action. It reduces food intake and attenuates the fall in metabolic rate associated with weight loss. The drug's neurochemical actions can also be distinguished from those of previous centrally acting anti-obesity agents. Clinical trials show that two out of three patients taking sibutramine lose >/= 5% weight and that the drug can enhance the maintenance of weight loss. Early weight loss predicts long-term success and can be used to guide clinical practice. To maximize the benefits of sibutramine, it is important that patients receive adjunctive diet and lifestyle therapy.
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PMID:Sibutramine: its mode of action and efficacy. 1245 97

The growing recognition of the health risks of obesity coupled with the difficulties in treating it successfully by lifestyle modification predicates a need for effective drug treatment. The history of drug treatment in the second half of the 20th century is, however, one of disappointment and concern over drug toxicity. However, the advances in our understanding of the mechanism of weight control, together with improved ways of evaluating anti-obesity drugs, has resulted in two effective compounds, sibutramine and orlistat, becoming available for clinical use. Sibutramine has actions on both energy intake and expenditure and had been shown to enhance weight loss and weight maintenance achieved by diet, in simple obesity as well as when accompanied by complications of diabetes or hypertension. About 50-80% of patients can achieve a >5% loss, significantly more than if patients receive the same lifestyle intervention with placebo. Orlistat, which acts peripherally to block the absorption of dietary fat, has had similar results in clinical trials; a recent study (XENDOS) has just reported results which show that the enhanced, albeit modest, weight loss achieved with orlistat delays the development of diabetes over a 4-year period. A number of other compounds are expected to complete or enter clinical trials over the next decade. There is considerable optimism that we will soon have the pharmacological tools needed to make the treatment of obesity feasible.
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PMID:Pharmacotherapy of obesity. 1246 17


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