orlistat and sibutramine

Multiple interventions are available to reduce excess body weight in children. We appraised the quality of evidence supporting each intervention and assessed the effectiveness on different obesity-related outcomes.. We conducted a systematic search for systematic reviews of randomized controlled trials evaluating pediatric obesity interventions applied for ≥6 months. We assessed the quality of evidence for each intervention using GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach.. From 16 systematic reviews, we identified 133 eligible randomized controlled trials. Physical activity interventions reduced systolic blood pressure and fasting glucose (low to moderate quality of evidence). Dietary interventions with low-carbohydrate diets had a similar effect to low-fat diets in terms of body mass index (BMI) reduction (moderate quality of evidence). Educational interventions reduced waist circumference, BMI, and diastolic blood pressure (low quality of evidence). Pharmacological interventions reduced BMI (metformin, sibutramine, orlistat) and waist circumference (sibutramine, orlistat) and increased high-density lipoprotein cholesterol (sibutramine) but also raised systolic and diastolic blood pressure (sibutramine). Surgical interventions (laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy) resulted in the largest BMI reduction (moderate quality of evidence). Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education significantly reduced systolic and diastolic blood pressure, BMI, and triglycerides. Combined parent-child interventions and parent-only interventions had similar effects on BMI (low quality of evidence).. Several childhood obesity interventions are effective in improving metabolic and anthropometric measures. A comprehensive multicomponent intervention, however, appears to have the best overall outcomes.

Topics: Adolescent; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Behavior Therapy; Blood Glucose; Blood Pressure; Body Mass Index; Child; Cholesterol, HDL; Cyclobutanes; Diet Therapy; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Exercise; Exercise Therapy; Gastrectomy; Gastric Bypass; Humans; Hypoglycemic Agents; Lactones; Metformin; Orlistat; Patient Education as Topic; Pediatric Obesity; Treatment Outcome; Triglycerides; Waist Circumference

All major guidelines on antihypertensive therapy recommend weight loss; anti-obesity drugs may be able to help in this respect.. To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction.. We obtained studies using computerised searches of the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, the clinical trials registry ClinicalTrials.gov, and from handsearches in reference lists and systematic reviews (status as of 13 April 2015).. Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long-term pharmacologic interventions for weight loss with placebo. . Two review authors independently selected studies, assessed risk of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of heterogeneity.. After updating the literature search, which was extended to include four new weight-reducing drugs, we identified one additional study of phentermine/topiramate, bringing the total number of studies to nine that compare orlistat, sibutramine, or phentermine/topiramate to placebo and thus fulfil our inclusion criteria. We identified no relevant studies investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion. No study included mortality and cardiovascular morbidity as predefined outcomes. Incidence of gastrointestinal side effects was consistently higher in those participants treated with orlistat versus those treated with placebo. The most frequent side effects were dry mouth, constipation, and headache with sibutramine, and dry mouth and paresthaesia with phentermine/topiramate. In participants assigned to orlistat, sibutramine, or phentermine/topiramate body weight was reduced more effectively than in participants in the usual-care/placebo groups. Orlistat reduced systolic blood pressure as compared to placebo by -2.5 mm Hg (mean difference (MD); 95% confidence interval (CI): -4.0 to -0.9 mm Hg) and diastolic blood pressure by -1.9 mm Hg (MD; 95% CI: -3.0 to -0.9 mm Hg). Sibutramine increased diastolic blood pressure compared to placebo by +3.2 mm Hg (MD; 95% CI: +1.4 to +4.9 mm Hg). The one trial that investigated phentermine/topiramate suggested it lowered blood pressure.. In people with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree, while phentermine/topiramate reduced body weight to a greater extent. In the same trials, orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We could include no trials investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. Long-term trials assessing the effect of orlistat, liraglutide, lorcaserin, phentermine/topiramate, or naltrexone/bupropion on mortality and morbidity are unavailable and needed. Rimonabant and sibutramine have been withdrawn from the market, after long-term trials on mortality and morbidity have confirmed concerns about the potential severe side effects of these two drugs. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while the application for European marketing authorisation for lorcaserin was withdrawn by the manufacturer after the Committee for Medicinal Products for Human Use judged the overall benefit/risk balance to be negative.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Blood Pressure; Cyclobutanes; Diet, Reducing; Female; Fructose; Humans; Hypertension; Lactones; Male; Middle Aged; Orlistat; Phentermine; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Safety-Based Drug Withdrawals; Time; Topiramate; Weight Loss

Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences.. To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents.. We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions.. We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants.. Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information.. This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials.

Topics: Adolescent; Anti-Obesity Agents; Body Mass Index; Child; Cyclobutanes; Fluoxetine; Humans; Lactones; Metformin; Orlistat; Pediatric Obesity; Randomized Controlled Trials as Topic

All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option.. To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause mortality - cardiovascular morbidity - adverse events. - changes in systolic and/or diastolic blood pressure - body weight reduction even though sibutramine and rimonabant have been withdrawn from the market.. Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews (status as of 17(th) August, 2012).. Randomized controlled trials in adult hypertensive patients with a study duration of at least 24 weeks comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo.. Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed-effect meta-analysis in the absence of significant heterogeneity between studies (p>0.1). Otherwise, we used the random effects method and investigated the cause of heterogeneity.. After the updated literature search, the number of studies remained the same, with eight studies comparing orlistat or sibutramine to placebo fulfilling our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm Hg.. In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine have been withdrawn from the market for the time being.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Cyclobutanes; Diet, Reducing; Female; Humans; Hypertension; Lactones; Male; Middle Aged; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Safety-Based Drug Withdrawals; Time; Weight Loss

Overweight and obesity have a major impact on global health; their prevalence has rapidly increased in all industrialized countries in the past few decades and diabetes and hypertension are their direct consequences. Pharmacotherapy provides reinforcement for obesity treatment, but should be an adjunctive support to diet, exercise, and lifestyle modification. At present, only orlistat and sibutramine have been approved by the US Food and Drug Administration for long-term use, but sibutramine was withdrawn for sale by the European Medicines Agency. The development of functional foods for the prevention and/or treatment of obesity suppose an opportunity for the food market and involve the knowledge of the mechanisms of appetite and energy expenditure as well as the metabolic sensation of satiety. Strategies for weight control management affect gut hormones as potential targets for the appetite metabolic regulation, stimulation of energy expenditure (thermogenesis), and modifications in the metabolic activity of the gut microbiota. Functional foods for obesity may also include bioactive fatty acids, phenolic compounds, soybean, plant sterols, dietary calcium, and dietary fiber. This review intends to offer an overview of the present situation of the anti-obesity agents currently used in dietary therapy as well as some functional food ingredients with potentially anti-obesity effects.

Topics: Anti-Obesity Agents; Calcium, Dietary; Cyclobutanes; Diet; Dietary Fiber; Energy Metabolism; Exercise; Fatty Acids, Unsaturated; Food Analysis; Food Handling; Glycine max; Humans; Lactones; Life Style; Obesity; Orlistat; Phytosterols; Polyphenols; United States; United States Food and Drug Administration; Weight Loss

Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question.

Topics: Anti-Obesity Agents; Appetite; Combined Modality Therapy; Comorbidity; Cost-Benefit Analysis; Cyclobutanes; Diabetes Mellitus, Type 2; Diet, Diabetic; Drug Combinations; Exercise Therapy; Fructose; Gastrointestinal Hormones; Humans; Incretins; Insulin; Insulin Secretion; Intestines; Lactones; Leptin; Life Style; Models, Biological; Neuropeptides; Obesity; Orlistat; Phentermine; Phytotherapy; Piperidines; Plant Preparations; Pyrazoles; Rimonabant; Topiramate

With the rising prevalence of childhood obesity, pediatricians are increasingly called upon to treat clinically overweight children. The primary treatment options are behavioral lifestyle modification, pharmacotherapy, and surgery. The cornerstone of childhood obesity treatment is lifestyle modification and has been shown to be effective in improving the severity of overweight and obesity. Several guidelines discuss appropriate methods for lifestyle modification in overweight and obese children. This review will summarize three recent guidelines/recommendations (released by the Scottish Intercollegiate Network, the American Academy of Pediatrics, and the United Kingdom National Institute for Health and Clinical Excellence) and describe by way of example, a current child obesity treatment program in the United States (Duke University Medical Center). Finally, evidence for pharmacologic and surgical treatment options will also be discussed, which can be valuable treatment options for select patients.

Topics: Adolescent; Bariatric Surgery; Behavior Therapy; Child; Child, Preschool; Combined Modality Therapy; Cooperative Behavior; Cyclobutanes; Energy Intake; Evidence-Based Medicine; Humans; Infant; Interdisciplinary Communication; Lactones; Life Style; Metformin; Motor Activity; Orlistat; Overweight; Pediatric Obesity; Pediatrics; Physician's Role; Practice Guidelines as Topic; Risk Factors; Young Adult

The study aims to compare anti-obesity interventions in a single evidence synthesis framework. Electronic databases were searched for randomized controlled trials of orlistat, rimonabant or sibutramine reporting weight or body mass index (BMI) change from baseline at 3, 6 or 12 months. A mixed treatment comparison was used to combine direct and indirect trial evidence. Ninety-four studies involving 24,808 individuals were included; 83 trials included data on weight change and 41 on BMI change. All results are in comparison with placebo. The active drugs were all effective at reducing weight and BMI. At 3 months, orlistat reduced weight by -2.65 kg (95% credibility interval -4.00 kg, -1.31 kg). For sibutramine, 15 mg gave a greater reduction than 10 mg at 12 months, -6.35 kg versus -5.42 kg, respectively. Rimonabant reduced weight by -11.23 kg at 3 months and -4.55 kg at 12 months. Lifestyle advice alone also reduced weight at 6 and 12 months, but was less effective than the pharmacological interventions. In conclusion, modest weight reductions were seen for all pharmacological interventions. Those interventions which have now been withdrawn from use (sibutramine and rimonabant) seem to be the most effective, implying that there may be a place in clinical practice for similar drugs if side effects could be avoided.

Topics: Anti-Obesity Agents; Body Mass Index; Cyclobutanes; Humans; Lactones; Life Style; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Treatment Outcome; Weight Loss

Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise.. To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients.. Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature.. A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin.. Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY.. The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses.. The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously.. The National Institute for Health Research Health Technology Assessment programme.

Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Cyclobutanes; Drug Costs; Exercise; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Piperidines; Primary Health Care; Pyrazoles; Rimonabant; Risk Reduction Behavior; Treatment Outcome

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.

Topics: Amides; Anti-Obesity Agents; Anticonvulsants; Antidepressive Agents; Basal Metabolism; Benzazepines; Benzoxazines; Body Mass Index; Bridged Bicyclo Compounds, Heterocyclic; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Combined Modality Therapy; Cyclobutanes; Dexfenfluramine; Fatty Acids; Female; Fenfluramine; Glucagon-Like Peptide 1; Human Growth Hormone; Humans; Intestinal Absorption; Lactones; Leptin; Life Style; Liraglutide; Male; Norepinephrine; Obesity; Obesity, Morbid; Orlistat; Piperidines; Pyrazoles; Pyridines; Receptor, Melanocortin, Type 4; Rimonabant; Satiation; Serotonin; Sodium-Glucose Transport Proteins; Sucrose; Thyroid Hormones

Topics: Animals; Cyclobutanes; Diabetes Mellitus; Female; Humans; Incretins; Insulin; Lactones; Male; Metformin; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Sex Characteristics; Sulfonylurea Compounds

Weight loss drugs have been developed to reduce the comorbidities associated with excess weight. We conducted a meta-analysis of the efficacy of orlistat and sibutramine on weight, body mass index, waist circumference and cardiovascular risk factors in overweight adolescents. MEDLINE and the Cochrane Library were searched for relevant articles using MESH terms and keywords. Studies were included if they had reported quantitative estimates and standard deviations of the association between each weight loss drug and weight, with information on at least one cardiovascular risk factor. A total of eight trials (three orlistat and five sibutramine) with information on 1391 individuals was included in the present analysis. The mean decrease in weight between the intervention and control groups was 5.25 kg (95% confidence interval: 3.03-7.48) after a minimum follow-up of 6 months. There was evidence of statistical heterogeneity between the studies (I(2) = 76%) that was no longer apparent after exclusion of trials of orlistat (mean weight decrease = 5.32 kg; I(2) = 38%). There was little evidence that treatment was associated with adverse effects on cardiovascular risk factors but this requires verification from future large trials with longer study follow-up.

Topics: Adolescent; Anti-Obesity Agents; Cardiovascular Diseases; Cyclobutanes; Humans; Lactones; Lipids; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Factors; Weight Loss

We undertook a meta-analysis of randomized controlled trials to summarize the efficacy of anti-obesity drugs in reducing BMI and improving health in children and adolescents. Data sources included Medline, Embase, the Cochrane controlled trials register and other registers of controlled trials, together with reference lists of identified articles. All data sources were searched from January 1996 to July 2008. We searched for double blind randomized placebo controlled trials of approved anti-obesity drugs used in children and adolescents (age < 20) with primary obesity for > or = 6 months. Six trials, 4 of sibutramine (total patients = 686) and 2 of orlistat (n = 573) met inclusion criteria. No trials of rimonabant were identified. Compared with placebo, sibutramine together with behavioural support reduced BMI by 2.20 kg/m(2) (95% CI: 1.57 to 2.83) and orlistat together with behavioural support reduced BMI by 0.83 kg/m(2) (95% CI 0.47 to 1.19). Sibutramine improved waist circumference, triglycerides and high density lipoprotein (HDL)-cholesterol, but raised systolic and diastolic blood pressure and pulse. Orlistat increased rates of gastrointestinal side-effects. We conclude that sibutramine in adolescents produces clinically meaningful reductions in BMI and waist circumference of approximately 0.63 SD, with improvements in cardiometabolic risk. Orlistat modestly reduces BMI (effect size approximately 0.24 SD) with a high prevalence of gastrointestinal adverse effects.

Topics: Adolescent; Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Child; Cognitive Behavioral Therapy; Combined Modality Therapy; Consumer Product Safety; Cyclobutanes; Female; Humans; Lactones; Male; Obesity; Orlistat; Randomized Controlled Trials as Topic; Treatment Outcome; Waist Circumference; Weight Loss

Previous meta-analyses investigating blood pressure effects of anti-obesity drugs have included studies using non-licensed doses, but not data from head-to-head studies. Furthermore, although diabetes is an important comorbidity in obesity, variation in blood pressure effects across diabetes status has not been investigated. The objective of this study was to estimate the effects on systolic (SBP) and diastolic blood pressure (DBP) of orlistat and sibutramine. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles from 1990 to February 2009 were searched. All placebo-controlled randomized controlled trials of 12-month duration or randomized head-to-head studies of any duration on adults using standard doses were included. Studies/study arms were excluded if they only evaluated weight maintenance after weight loss. Randomized controlled trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Random effects models were used for assessment of weighted mean differences. Eighteen placebo-controlled (12 orlistat, 5540 patients; 6 sibutramine, 1495 patients) and four head-to-head trials (348 patients) met the inclusion criteria. Three orlistat and three sibutramine studies examined overweight subjects with type 2 diabetes (T2DM), as did two head-to-head trials. Mean baseline SBP ranged from 119 to 153 mmHg, and mean DBP from 69 to 98 mmHg. Overall, the placebo-controlled SBP change was -1.9 (95% CI; -2.7, -1.1) mmHg for orlistat, and 0.5 (-1.1, 2.1) mmHg for sibutramine. The corresponding values for DBP were -1.5 (-2.2, -0.8) and 1.7 (0.7, 2.6). Compared with patients without diabetes, diabetic patients treated with orlistat experienced smaller and non-significant reductions of SBP (-0.9; -2.6, 0.7 vs. -2.2; -3.0, -1.3) and DBP (-1.0; -2.4, 0.3 vs. -1.6; -2.4, -0.8). For sibutramine, higher on-treatment elevations in SBP (1.6; -1.3, 4.5 vs. 0.1; -1.8, 2.0) and DBP (2.4; 0.6, 4.1 vs. 1.4; 0.3, 2.5) were seen in patients with vs. without diabetes. In head-to-head trials, the overall differences between sibutramine and orlistat were small and non-significant for both SBP (1.0; -2.3, 4.3) and DBP (-0.2; -2.9, 2.5). In conclusion, in the studies using approved sibutramine doses, the drug caused significant elevations in DBP, while the overall SBP effect was near null. Moreover, absence of a blood pressure-lowering effect of orlistat ad a higher DBP elevation by sibutramine were observed for per

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Lactones; Middle Aged; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Targeted systematic review to support the updated US Preventive Services Task Force (USPSTF) recommendation on screening for obesity in children and adolescents.. To examine the benefits and harms of behavioral and pharmacologic weight-management interventions for overweight and obese children and adolescents.. Our data sources were Ovid Medline, PsycINFO, the Education Resources Information Center, the Database of Abstracts of Reviews of Effects, the Cochrane databases, reference lists of other reviews and trials, and expert recommendations. After 2 investigators reviewed 2786 abstracts and 369 articles against inclusion/exclusion criteria, we included 15 fair- to good-quality trials in which the effects of treatment on weight, weight-related comorbidities, and harms were evaluated. Studies were quality rated by 2 investigators using established criteria. Investigators abstracted data into standard evidence tables.. In the available research, obese (or overweight) children and adolescents aged 4 to 18 years were enrolled, and no studies targeted those younger than 4 years. Comprehensive behavioral interventions of medium-to-high intensity were the most effective behavioral approach with 1.9 to 3.3 kg/m(2) difference favoring intervention groups at 12 months. More limited evidence suggests that these improvements can be maintained over the 12 months after the end of treatments and that there are few harms with behavioral interventions. Two medications combined with behavioral interventions resulted in small (0.85 kg/m(2) for orlistat) or moderate (2.6 kg/m(2) for sibutramine) BMI reduction in obese adolescents on active medication; however, no studies followed weight changes after medication use ended. Potential adverse effects were greater than for behavioral interventions alone and varied in severity. Only 1 medication (orlistat) has been approved by the US Food and Drug Administration for prescription use in those aged > or =12 years.. Over the past several years, research into weight management in obese children and adolescents has improved in quality and quantity. Despite important gaps, available research supports at least short-term benefits of comprehensive medium- to high-intensity behavioral interventions in obese children and adolescents.

Topics: Adolescent; Appetite Depressants; Behavior Therapy; Child; Child, Preschool; Counseling; Cyclobutanes; Female; Humans; Lactones; Obesity; Orlistat; Overweight; Primary Health Care; Treatment Outcome

This article examines the transitions in pharmacological therapy for obesity. It reviews the current options approved by the Food and Drug Administration and several drugs approved for other indications that can be used to treat obesity as well. Because weight regulation is complex and redundant systems protect against perceived starvation, optimal treatment of obesity in individual patients will likely require different combinations of behavioral, nutritional, pharmacologic, endoscopic, and surgical therapies.

Topics: Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Benzazepines; Bupropion; Cyclobutanes; Ephedrine; Fenfluramine; Humans; Lactones; Naltrexone; Obesity; Orlistat; Phentermine; Weight Gain; Weight Loss

Roughly two thirds of U.S. adults are overweight or obese. Obesity increases the risk of hypertension, type 2 diabetes mellitus, hyperlipidemia, heart disease, pulmonary disease, hepatobiliary disease, cancer, and a number of psychosocial complications. Physicians often feel unprepared to handle this important problem. Practical office-based strategies include: (1) making recommendations for assisted self-management, including guidance on popular diets, (2) advising patients about commercial weight-loss programs, (3) advising patients about and prescribing medications, (4) recommending bariatric surgery, and (5) supplementing these strategies with counseling about lifestyle changes using a systematic approach. Family physicians should provide basic information about the effectiveness and safety of popular diets and commercial weight-loss programs, and refer patients to appropriate information sources. Sibutramine and orlistat, the only medications currently approved for the long-term treatment of obesity, should only be prescribed in combination with lifestyle changes. Bariatric surgery is an option for adults with a body mass index of 40 kg per m2 or higher, or for those with a body mass index of 35 kg per m2 or higher who have obesity-related comorbidities such as type 2 diabetes. The five A's behavioral counseling paradigm (ask, advise, assess, assist, and arrange) can be used as the basis for a systematic, practical approach to the management of obesity that incorporates evidence for managing common obesity-related behaviors.

Topics: Adult; Anti-Obesity Agents; Bariatric Surgery; Body Mass Index; Child; Counseling; Cyclobutanes; Diet, Reducing; Female; Humans; Lactones; Male; Obesity; Orlistat; Risk Factors

Anorexia nervosa and bulimia nervosa are significant mental health problems in the adolescent population; however, there are no medications approved by the FDA for the treatment of adolescents with either of these disorders. Many medications are used off label for both the symptoms of eating disorders and their co-morbid conditions, particularly SSRIs and atypical anti-psychotics. The dosing, side effect profile, and long term effects of these medications in children and adolescents is unclear. Binge eating disorder, night eating syndrome, and sleep-related eating disorder often are associated with over-weight in adolescents. There are various pharmacological approaches to the treatment of obesity in the adolescent population some of which have FDA approval. In the article the authors discuss pharmacological approaches to guide the treatment of eating disorders and obesity in the pediatric population, including risks of treatment, monitoring of potential side effects, and recent outcomes in the literature.

Topics: Adolescent; Anorexia Nervosa; Anticonvulsants; Antipsychotic Agents; Appetite Depressants; Behavior Therapy; Bulimia Nervosa; Child; Combined Modality Therapy; Cyclobutanes; Feeding and Eating Disorders; Humans; Lactones; Obesity; Orlistat; Psychotropic Drugs; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors

Obesity is one of the greatest public health challenges of the twenty-first century. The World Health Organization (WHO) reports that in 2005 approximately 1.6 billion adults were overweight and at least 400 million adults were obese. The prevalence of obesity is still continuing to increase dramatically. Overweight and obese people carry a higher risk for a variety of cardiovascular diseases including hypertension, coronary heart disease, stroke and peripheral occlusive artery disease. Weight loss is considered to be the initial step which helps to prevent or to control the clinical consequences of obesity. In a great number of patients who are not able to reduce weight by means of non-pharmacological measures, drug therapy can assist in reaching the weight management targets. Drug treatment should only be considered as part of a systematic weight management program including dietary and lifestyle changes. This review summarizes current pharmacotherapeutic concepts for the treatment of obesity in adults focusing on efficacy and safety of anti-obesity drugs.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Combined Modality Therapy; Cyclobutanes; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat; Piperidines; Prevalence; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Risk Reduction Behavior; Treatment Outcome; Weight Loss

Obesity is considered a worldwide epidemic. Weight reduction by means of lifestyle changes is difficult to achieve, and pharmacotherapy is frequently needed. Although all currently approved anti-obesity agents have proven to be effective to achieve some degree of weight reduction and improve cardiometabolic risk factors, different compounds differ in their mechanism of action and safety profile. However, it is still difficult to achieve and maintain therapeutic objectives along time. The aim of the present article is to summarize the main characteristics of available anti-obesity agents and to explore novel agents that may provide significant clinical benefits in the future.

Topics: Animals; Anti-Obesity Agents; Cardiovascular Diseases; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant

Obesity is considered as a major health problem, as its prevalence continuously rises worldwide. One of the common health consequences of obesity is type 2 diabetes mellitus. Therefore, antiobesity management is a prerequisite in treating diabetic patients. Lifestyle modifications combined with pharmacological agents appear to be an effective approach. Sibutramine is a serotonin-noradrenaline reuptake inhibitor, which acts centrally by promoting the feeling of satiety and decreasing caloric intake, thus resulting in weight loss. A potential association with cardiovascular side effects has been noted. Orlistat, a gastric and pancreatic lipase inhibitor, also achieves significant weight loss and improves glycaemic status, but it has gastrointestinal side effects. Rimonabant, the first endocannabinoid CB1 antagonist, is associated with weight reduction and it improves diabetic parameters; nevertheless, it is associated with psychiatric disorders; indeed, a recently conducted safety review led to the temporal suspension of its commercialization. The above-mentioned medications seem to be currently useful agents for treating obesity in patients with type 2 diabetes mellitus. Other medications used for diabetes management, such as exenatide, liraglutide and pramlintide, have also shown body weight reduction. Ongoing research is needed to scrutinize the precise impact of these agents in the daily clinical practice of management of obesity in patients with type 2 diabetes mellitus.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Body Weight; Cyclobutanes; Diabetes Mellitus, Type 2; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Receptor, Cannabinoid, CB1; Rimonabant; Treatment Outcome; Weight Loss; Young Adult

The objective of this article was to estimate the risk of discontinuation due to adverse events in trials of orlistat, sibutramine and rimonabant. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles were searched from 1990 to May 2008. All randomized placebo-controlled trials of 12-24 months of duration on adults using licensed doses were included. Studies/study arms were excluded if they evaluated weight maintenance after weight loss. Trials were identified, subjected to inclusion and exclusion criteria and reviewed. Data on participants, interventions and discontinuation were extracted and trials rated for quality based on established criteria. A random effects model was used to estimate pooled risk ratios, risk differences and number needed to harm (NNH). A total of 28 trials met the inclusion criteria (16 orlistat, 7 sibutramine and 5 rimonabant). The risk ratios for discontinuation due to adverse events were significantly elevated for rimonabant (2.00; 1.66-2.41) and orlistat (1.59; 1.21-2.08), but not sibutramine (0.98, 0.68-1.41). Compared with placebo, the risk difference was the largest for rimonabant (7%, 5-9%; NNH 14, 11-19), followed by orlistat (3%, 1-4%; NNH 39, 25-83), while no significant difference was seen for sibutramine (0.2%, -3 to 4%; NNH 500). The most common adverse events leading to withdrawal were gastrointestinal for orlistat (40%) and psychiatric for rimonabant (47%). Corresponding information was unavailable for sibutramine. In conclusion, available weight loss drugs differ markedly regarding risk of discontinuation due to adverse events, as well as in underlying causes of these events. Given the large number of patients eligible for treatment, the low NNH for rimonabant is a concern.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Medication Adherence; Odds Ratio; Orlistat; Overweight; Patient Dropouts; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant

Ancillary therapies for weight management, consisting mainly of diet and exercise programs that incorporate variable levels of lifestyle modification techniques, are frequently ineffective to achieve clinically meaningful weight loss and maintenance. Although pharmacological treatment of obesity is widely used in most countries, the number of available drugs is still very limited. The most widely used anti-obesity agents are sibutramine and orlistat, both available in clinical practice for about a decade. A large number of clinical trials have demonstrated that both agents are safe and well tolerated, with a level of efficacy in the moderate weight loss recommended by the most relevant clinical guidelines. Several studies have assessed the efficacy and safety of sibutramine and orlistat in adolescents and also for the treatment of some associated conditions in adults, including type 2 diabetes, polycystic ovary syndrome and binge eating disorder. The positive results of these studies suggest an expanding role for both agents, not only for the treatment of obesity, but also for associated conditions. After the efficacy of orlistat for the prevention of type 2 diabetes demonstrated in the XENDOS study, the results of SCOUT study are awaited for a better evaluation of sibutramine impact on cardiovascular outcomes.

Topics: Adolescent; Adult; Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Evidence-Based Medicine; Humans; Lactones; Obesity; Orlistat; Practice Guidelines as Topic; Weight Loss

All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option.. To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause mortality - cardiovascular morbidity - adverse events. - changes in systolic and/or diastolic blood pressure - body weight reduction. Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews.. Randomized controlled trials in adult hypertensive patients with a study duration of at least 24 weeks comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo.. Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed-effect meta-analysis in the absence of significant heterogeneity between studies (p>0.1). Otherwise, we used the random effects method and investigated the cause of heterogeneity.. Eight studies comparing orlistat or sibutramine to placebo fulfilled our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm Hg.. In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are needed.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Cyclobutanes; Female; Humans; Hypertension; Lactones; Male; Middle Aged; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Time; Weight Loss

Obesity is epidemic; new medications and therapeutic options are urgently needed to reduce the associated health care burden. The initial clinical strategy for weight loss is lifestyle modification involving a combination of diet, exercise, and behavior change. However, it is difficult for many to achieve and maintain weight loss solely through this approach. Only two drugs, orlistat and sibutramine, have been approved by the US Food and Drug Administration (FDA) to treat obesity long term, and both medications have undesirable side effects, leaving an enormous unmet need for efficacious and safe therapy for obesity. Other medications with weight-loss effects have been approved by the FDA for short-term treatment of obesity or for disorders other than obesity, but these also have potential adverse effects. This article discusses the perceived benefits and risks of these approved medications along with emerging drugs that have shown weight-loss effects.

Topics: Anti-Obesity Agents; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Weight Loss

Weight gain, during and after the menopause is common. Contributing factors include ethnicity, reduced physical activity, reduced lean mass, reduced resting metabolic rate and treatment with certain drugs, e.g. steroids, insulin, glitazones. Excess body weight increases the risk of medical conditions including type 2 diabetes, hypertension, osteoarthritis, certain cancers and is associated with increased mortality. This review examines pharmacological approaches to promote weight loss. Pharmacological therapy should be considered as an adjunct to diet and lifestyle changes. The licensed drugs orlistat, sibutramine and rimonabant are discussed. Obesity increases the risk of type 2 diabetes. Thus, the effects of metformin and exenatide are examined.

Topics: Anti-Obesity Agents; Bariatric Surgery; Cyclobutanes; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Lactones; Menopause; Metformin; Obesity; Orlistat; Peptides; Piperidines; Pyrazoles; Rimonabant; Risk Factors; Venoms

To review economic evaluations of weight loss drugs and compare reported incremental cost-effectiveness ratios (ICERs).. A literature search was conducted for cost-effectiveness (CEAs) and cost-utility analyses (CUAs) of sibutramine, orlistat and rimonabant.. Fourteen unique articles were identified (11 CUAs and 3 CEAs; 9 orlistat, 4 sibutramine and 1 rimonabant). All used diet and exercise as comparator, whereas none included indirect costs. Time horizons varied from treatment period only (1-4 years) to 80 years (median 7.5 years). Longer studies modeled effects on diabetes, micro- and macrovascular complications, coronary heart disease and death. Of the CUAs, the median ICER was 16,000 euro(2007)/QALY (quality-adjusted life-year; range 10,000-88,000), with the worst cost-effectiveness when recommended stop rules for non-responding patients were not applied. All studies but three were funded by the manufacturing company, and the median ICER was considerably higher for independent than for sponsored analyses (62,000 euro vs 15,000 euro/QALY). However, two of the three independent CUAs did not use recommended stop rules, as compared with one of eight manufacturer-sponsored analyses. The results were most sensitive to assumptions regarding weight loss sustainability and utility per kilogram lost. Side effects and dropout because of reasons other than lack of efficacy were generally not incorporated.. Published economic evaluations indicate that orlistat, sibutramine and rimonabant are within the range of what is generally regarded as cost-effective. Uncertainty remains about weight loss sustainability, utility gain associated with weight loss and extrapolations from transient weight loss to long-term health benefits. Modeling of head-to-head comparisons and attrition is needed, as are analyses conducted independently of manufacturing companies.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Cost-Benefit Analysis; Cyclobutanes; Europe; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Quality-Adjusted Life Years; Rimonabant; Treatment Outcome; United States

To examine available behavioral, pharmacological, and surgical weight management interventions for overweight (defined as BMI > 85th to 94th percentile of age and sex-specific norms) and/or obese (BMI > 95th percentile) children and adolescents in clinical and nonclinical community settings.. We identified two good quality recent systematic reviews that addressed our research questions. We searched Ovid MEDLINE, PsycINFO, Database of Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Education Resources Information Center from 2005 (2003 for pharmacological studies) to December 11, 2007, to identify literature that was published after the search dates of prior relevant systematic reviews; we also examined reference lists of five other good-quality systematic reviews and of included trials, and considered experts' recommendations. We identified two good quality systematic reviews and 2,355 abstracts from which we identified 45 primary studies and trials that addressed our research questions.. After review by two investigators against pre-determined inclusion/exclusion criteria, we included existing good-quality systematic reviews, fair-to-good quality trials, and case series (for bariatric surgeries only) to evaluate the effects of treatment on weight and weight-related co-morbidities; we would have included large comparative cohort studies to evaluate longer term followup and harms of behavioral and pharmaceutical treatment and noncomparative cohort studies for surgical treatments if they had been available. Investigators abstracted data into standard evidence tables with abstraction checked by a second investigator. Studies were quality-rated by two investigators using established criteria.. Available research primarily enrolled obese (but not overweight) children and adolescents aged 5 to 18 years and no studies targeted those less than 5 years of age. Behavioral interventions in schools or specialty health care settings can result in small to moderate short-term improvements. Absolute or relative weight change associated with behavioral interventions in these settings is generally modest and varies by treatment intensity and setting. More limited evidence suggests that these improvements can be maintained completely (or somewhat) over the 12 months following the end of treatments and that there are few harms with behavioral interventions. Two medications (sibutramine, orlistat) combined with behavioral interventions can result in small to moderate short-term weight loss in obese adolescents with potential side effects that range in severity. Among highly selected morbidly obese adolescents, very limited data from case series suggest bariatric surgical interventions can lead to moderate to substantial weight loss in the short term and to some immediate health benefits through resolution of comorbidities, such as sleep apnea or asthma. Harms vary by procedure. Short-term severe complications are reported in about 5 percent and less severe short-term complications occur in 10 to 39 percent. Very few cases provide data to determine either beneficial or harmful consequences more than 12 months after surgery.. The research evaluating the treatment of obese children and adolescents has improved in terms of quality and quantity in the past several years. While there are still significant gaps in our understanding of obesity treatment in children and adolescents, the current body of research points the way to further improvements needed to inform robust policy development. Publication of additional research and policy activities by others, including the U.S. Preventive Services Task Force, is expected in the near future. And, in considering this important public health issue, policymakers should not ignore the importance of obesity prevention efforts as well as treatment.

Topics: Adolescent; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Behavior Therapy; Child; Child, Preschool; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Weight Loss

To investigate, through a meta-analysis of clinical trials, the effect of two weight-reducing drugs, such as orlistat and sibutramine, on serum lipid profiles in overweight and obese subjects, independently of weight loss.. A systematic search strategy, incorporating the terms orlistat, sibutramine, fat, cholesterol, lipid profile, cardiovascular risk, was developed to identify randomized trials in MEDLINE from inception to the end of May 2005. Trial selection was limited by language of publication (English) and duration (6-12 months).. Fifteen and ten randomized, double-blind, placebo-controlled trials on orlistat and sibutramine respectively, were eligible for inclusion. In the 15 trials with orlistat, mean weight loss showed a significant correlation with mean reduction of total cholesterol (r=0.48; p<0.05), which maintained statistical significance after adjustment for mean weight loss (B=-2.81+/-1.28; p<0.05). Conversely, in the ten trials with sibutramine, treatment was not associated with a significant decrease in cholesterol levels after adjustment for weight loss (B=3.25+/-4.13; p not significant).. Orlistat or sibutramine, when individually compared to placebo, are effective in promoting significant weight loss. In addition, orlistat determines a significant reduction of total cholesterol, independent of weight loss itself. These observations indicate that orlistat is a useful adjunctive tool for improving cardiovascular risk factor profiles in overweight and obese patients.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Cyclobutanes; Humans; Hyperlipidemias; Hypolipidemic Agents; Lactones; Lipids; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

Diet, exercise and behavioral therapy are the basics for every treatment of obesity. If lifestyle intervention does not result in a weight loss of 5% within 3 to 6 months, an additional pharmacotherapy can be considered. Treated patients should have a BMI >/=30 kg/m(2) or at least a BMI >/=27 kg/m(2) plus accompanying comorbidities, such as type 2 diabetes, dyslipidemia or hypertension. Current guidelines list orlistat, sibutramine and rimonabant as possible options for the pharmacotherapy of obesity. These compounds result in moderate weight reduction and improvement of cardiovascular risk profile. Especially the improvement of glucose metabolism can be considered as clinically relevant. Different side effects of the various compounds need to be considered before their use. Additional options for the pharmacotherapy of obesity are currently developed, their approval, however, is unlikely to happen within the next couple of years.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Treatment Outcome

Randomized controlled trials (RCTs) directly comparing weight loss drugs approved in the European Union were reviewed and the results analysed by meta-analysis. Eight RCTs including 885 patients were found comparing weight loss of orlistat and sibutramine, while no study including rimonabant was found. The median study duration was 7 months (range 3-12). Four of the seven studies comparing sibutramine and orlistat mono-therapy showed that sibutramine was significantly more efficacious for weight loss, while the remaining three showed equivalence. The weighted mean difference in weight loss was 2.2 kg (95% CI 0.5-3.9) favouring sibutramine. Three studies investigated orlistat and sibutramine as combination therapy, and two found it to be significantly better than orlistat alone, but not better than sibutramine alone. Based on these head-to-head RCT data, sibutramine appears to be significantly more efficacious for achieving weight loss than orlistat. This is concordant with indirect evidence from previous meta-analyses, where the respective compounds were compared with placebo. Only four studies reported attrition, and the pooled risk ratio was 0.6 (0.3-1.4) indicating lower dropout for sibutramine. This information together with an understanding of the clinical properties of each drug should help to guide the prescribing physician in the selection of adequate drug therapy for obesity.

Topics: Anti-Obesity Agents; Cyclobutanes; Female; Humans; Lactones; Male; Obesity; Orlistat; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss

The prevalence of obesity in the developed world is increasing. Approximately 23% of adult Canadians (5.5 million people) are obese. Obesity is associated with an increased risk of developing several comorbid diseases, ranging from cardiovascular diseases to cholelithiasis and nonalcoholic fatty liver disease. The etiology of obesity is multifactorial, involving a complex interaction among genetics, hormones and the environment. The available evidence and recommendations for nonpharmacological management of obesity, including dietary therapy, physical activity and behavioural therapy, in addition to pharmacotherapy are discussed. A brief discussion on endoscopic and surgical procedures is undertaken. Several antiobesity treatment options are available and may be indicated in appropriate situations. Selecting obesity therapy may be guided by body mass index measurements, comorbid illnesses and patient preference.

Topics: Anti-Obesity Agents; Bariatric Surgery; Behavior Therapy; Caloric Restriction; Cyclobutanes; Dietary Carbohydrates; Dietary Fats; Exercise; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Weight Loss

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

Weight loss is recommended in all major guidelines for antihypertensive therapy. We searched for randomized controlled trials investigating the effects of weight-reducing diets, pharmacologic substances, and invasive interventions for weight reduction on patient-relevant end points and blood pressure (BP) in patients with essential hypertension. No information on the effects on patient-relevant end points was available. Patients assigned to weight loss diets, orlistat, or sibutramine reduced their body weight more effectively than did patients in the usual care/placebo groups. Reduction of BP was higher in patients treated with weight loss diets (systolic BP [SBP]: weighted mean difference [WMD], -6.3 mm Hg; diastolic BP [DBP]: WMD, -3.4 mm Hg) or orlistat (SBP: WMD, -2.5 mm Hg; DBP: WMD, -2.0 mm Hg). Systolic BP increased with sibutramine treatment (WMD, 3.2 mm Hg). In patients with essential hypertension, therapy with a weight loss diet or orlistat resulted in reductions in body weight and BP. Although sibutramine treatment reduced body weight, it did not lower BP.

Topics: Appetite Depressants; Blood Pressure; Cyclobutanes; Humans; Hypertension; Lactones; Obesity; Orlistat; Time Factors; Treatment Outcome; Weight Loss

The unabated rise in the prevalence of obesity is a challenge for global health care systems. Efforts to reverse this trend by dietary or behavioral counseling have not been successful, which has stimulated efforts to find a role for pharmacotherapy. Currently only a small number of antiobesity drugs are approved for long-term use and only a few compounds are in clinical development. Despite recent progress in the understanding of the regulation of energy balance, drug discovery has been less productive than expected. In the present review, the clinically available antiobesity agents are discussed. Examples of drug candidates that are currently in development are given and the possible future range of antiobesity agents is illustrated by the targets being addressed in drug discovery. Finally, the efficacy of antiobesity agents and their value in the treatment of obesity are assessed in comparison with other therapeutic approaches, such as surgery and changes in lifestyle.

Topics: Anti-Obesity Agents; Cyclobutanes; Disease Outbreaks; Drug Design; Drugs, Investigational; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant

Antiobesity treatment is recommended for selected patients in whom lifestyle modification is unsuccessful. Two antiobesity drugs are currently licensed for long-term use. Orlistat, a gastrointestinal lipase inhibitor, reduces weight by around 3 kg on average and decreases progression to diabetes in high-risk patients; adverse gastrointestinal effects are common. Sibutramine, a monoamine-reuptake inhibitor, results in mean weight losses of 4-5 kg, but is associated with increases in blood pressure and pulse rate. Rimonabant, the first of the endocannabinoid receptor antagonists, reduces weight by 4-5 kg on average and improves waist circumference and concentrations of HDL cholesterol and triglyceride; however, an increased incidence of mood-related disorders has been reported. To date, all antiobesity drug trials have been limited by their high attrition rates and lack of long-term morbidity and mortality data. Other promising antiobesity drugs, including those acting within the central melanocortin pathway, are in development, but are years away from clinical use. In light of the lack of successful weight-loss treatments and the public-health implications of the obesity pandemic, the development of safe and effective drugs should be a priority. However, as new drugs are developed we suggest that the assessment processes should include both surrogate endpoints (ie, weight loss) and clinical outcomes (ie, major obesity-related morbidity and mortality). Only then can patients and their physicians be confident that the putative benefits of such drugs outweigh their risks and costs.

Topics: Anti-Obesity Agents; Blood Pressure; Cholesterol, HDL; Cyclobutanes; Half-Life; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Weight Loss

The currently available drugs for long-term treatment of obesity are sibutramine and orlistat. They have been shown to be able to induce significant weight loss, with important co-morbidity reduction, allowing the maintenance of reduced body weight for at least 1-2 years. Cardiostimulating and gastrointestinal adverse effects are however not negligible.

Topics: Anti-Obesity Agents; Body Weight; Cyclobutanes; Energy Metabolism; Exercise; Humans; Lactones; Obesity; Orlistat

Most patients with type 2 diabetes mellitus are overweight or obese, and the relation between obesity, especially of the visceral compartment, and the risk for developing diabetes is well recognized. Excessive adipose tissue is associated with insulin resistance as well as the increased expression of proinflammatory cytokines and prothrombotic factors, all of which contribute to elevating the risk for coronary artery disease (CAD). In particular, abdominal obesity, or excess visceral adiposity, has been linked to a cluster of risk factors (high blood pressure, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and impaired fasting glucose) that constitute the metabolic syndrome, the presence of which confers an increased risk for type 2 diabetes and cardiovascular disease. In fact, a large waist circumference, a surrogate measure of abdominal adiposity, is 1 of the main criteria for diagnosing the metabolic syndrome. Lifestyle modification is the first-line approach to the management of obesity and the metabolic syndrome. However, if patients are unable to achieve a weight loss of 5%-10% of initial body weight and improve cardiometabolic risk factors with lifestyle modification alone, physicians should consider using adjunctive long-term pharmacotherapy. A variety of approved and investigational pharmacologic agents, including sibutramine, orlistat, metformin, and rimonabant, have been shown to reduce weight and ameliorate metabolic syndrome components, thereby reducing cardiovascular risk. Such global risk reduction is crucial for patients with diabetes, in whom CAD is a major cause of mortality.

Topics: Anti-Obesity Agents; Cannabinoid Receptor Antagonists; Cardiovascular Diseases; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Lactones; Life Style; Obesity; Orlistat

Excessive adipose tissue is associated with increased expression or suppression of cytokines and hormones, leading to inflammation and chronic disease. In particular, abdominal adiposity, as evidenced by a high waist circumference, is a component of the metabolic syndrome, a constellation of risk factors (e.g., high waist circumference, high blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, elevated fasting glucose) that increases the risk for type 2 diabetes and cardiovascular disease. Lifestyle modification is the first-line approach to the management of obesity and the metabolic syndrome. However, for patients who cannot achieve a reduction in weight (5% to 10% of initial body weight) and cardiometabolic risk factors with lifestyle modification alone, physicians should consider adjunctive long-term pharmacotherapy. A variety of approved and investigational pharmacologic agents have been shown to reduce weight and modify metabolic syndrome components, including sibutramine, orlistat, metformin, and rimonabant. Data from four phase 3 trials suggest that rimonabant, the first cannabinoid receptor inhibitor, modulates cardiometabolic risk factors, both through its impact on body weight and through direct pathways that are not related to weight loss.

Topics: Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Cyclobutanes; Humans; Hypoglycemic Agents; Lactones; Metabolic Syndrome; Obesity; Orlistat; Practice Guidelines as Topic; Receptor, Cannabinoid, CB1; Weight Loss

The present article reviews the diagnostic criteria for pediatric obesity and its comorbidities. Treatment is also reviewed, including promotion of physical activity, and dietetic, pharmacologic and surgical treatment.

Topics: Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Child; Combined Modality Therapy; Cyclobutanes; Fatty Liver; Gastric Bypass; Humans; Hypercholesterolemia; Hypertension; Insulin Resistance; Lactones; Metabolic Syndrome; Obesity; Orlistat; Risk Factors

Treatment of obesity continues to rely upon the classical triad of nutritional advise, increase of physical activity and use of drugs. However, in recent years, there have appeared novelties in both therapeutic targets and new molecules. With regard to therapeutic targets of obesity, success does not consist of losing much weight but attaining a moderate yet maintained weight lose (5-10% of initial weight) at the expense of visceral fat. In other words, instead of weight, what is needed is a waist reduction, mainly to improve or prevent obesity-related metabolic and vascular complications. Regarding drugs, a new molecules is about to appear in the international pharmaceutical market: rimonabant. A selective blocker of the endocannabinoid receptor CB1, it has proven to be effective and safe in treating obesity and its comorbidities. Another known agent, orlistat, has proven to be effective in the prevention of the development of type 2 diabetes in obese patients with or without glucose intolerance.

Topics: Anti-Obesity Agents; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant

Three medications with approval for long-term use in the treatment of obesity are currently available in the United States. Sibutramine (U.S. Food and Drug Administration [FDA] approved in 1997), orlistat (FDA approved in 1999), and rimonabant (available in Europe and given FDA approvable status in 2006 and expected to be marketed in 2007) represent modern approaches to medications used adjunctively for weight management. As demonstrated in large clinical trials of 2 to 4 years' duration, these medications significantly increase weight loss compared with placebo; weight loss with these drugs reaches a nadir between 20 and 28 weeks; weight loss, averaged 8%-10%, with the placebo contributing 4%-6% of that. Weight maintenance is demonstrated as long as adherence to medication continues. All medications have side effects that need to be considered. For sibutramine, there is a rise in blood pressure and heart rate that may require discontinuation of the drug in a small percent of patients. For orlistat, steatorrhea produces the principal gastrointestinal side effects. Rimonabant appears to have a favorable safety and tolerability profile. Nausea and gastrointestinal symptoms are the chief tolerability issue, but they are usually self-limited. In addition there are several drugs and drug combinations in phase 2 or phase 2 trials that will be reported on in the coming years.

Topics: Animals; Anti-Obesity Agents; Clinical Trials, Phase II as Topic; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Overweight; Piperidines; Pyrazoles; Rimonabant; Treatment Outcome

To evaluate the safety and efficacy of current pharmacotherapeutic options for weight loss in overweight adolescents.. Literature was obtained through MEDLINE Ovid (1996-April 2007) and EMBASE Drugs and Pharmacology (1991-2nd quarter 2007) searches and a bibliographic review of published articles. Key words included adolescents, overweight, obesity, anti-obesity agents, drug therapy, orlistat, sibutramine, and metformin.. All studies published in the English language that evaluated the use of pharmacotherapy for the treatment of overweight adolescents were critically analyzed; pertinent articles were selected for this review.. Orlistat has been approved for use in adolescents between the ages of 12 and 16 years. The most frequently reported adverse effects of orlistat were gastrointestinal; reduced concentrations of fat-soluble vitamins were also observed. Of the 6 clinical trials published, 5 have shown statistically significant reductions in body mass index (BMI) from baseline, ranging from 0.55 to 4.09 kg/m2; one small trial failed to demonstrate significant weight reduction compared with placebo. Sibutramine has also been evaluated for use in overweight adolescents in 6 trials. Trials demonstrated a statistically significant reduction in BMI up to 5.6 kg/m2 (from baseline). Of concern is evidence indicating that sibutramine therapy may be associated with elevated blood pressure, increased pulse rate, depression, and suicidal ideations. Lastly, metformin has recently been evaluated for weight loss in overweight adolescents; small, short-term trials demonstrate modest reductions in weight and BMI.. Orlistat has been proven both safe and effective for weight reduction in overweight adolescents. Sibutramine has also been proven effective in reducing weight in this population; however, the potential for severe adverse effects requires further investigation. Metformin has demonstrated promising results in small trials; its role in the treatment of overweight adolescents will remain investigational until further research is conducted.

Topics: Adolescent; Anti-Obesity Agents; Clinical Trials as Topic; Cyclobutanes; Humans; Hypoglycemic Agents; Lactones; Metformin; Obesity; Orlistat; Overweight

Modification of lifestyle is the main therapeutical approach in the treatment of obesity, but use to fail on long terms of time. Addition of anti-obesity drugs allows keeping the weight loss during years and improving obesity-related comorbidities.. This review is an actualisation on efficacy, safety and tolerability of the approved drugs on the long-term treatment of obesity (orlistat and sibutramine). New indications and effects of their use far beyond the weight loss are as well commented. Finally, potential benefits of the administration of CB1 antagonist rimonabant on the weight loss and cardiometabolic risk factors are analysed in detail.. A decade of experience on the use of orlistat and sibutramine has demonstrated their higher efficacy on the weight loss when compared to placebo either on adult or teenage population as well as safety and tolerability on long-term administration. Beneficial effects on the lipid profile, glycosilated haemoglobin on diabetic patients, blood pressure and levels of inflammatory cytokines, contribute to decrease the cardiovascular risk on obese patients. Phase III clinical trials using rimonabant show additional benefits to the expected weight loss, mainly reducing visceral fat and cardiometabolic risk factors.. Pharmacological treatment of obesity must be considered as a therapeutical tool that has to be used together with long-term lifestyle changes, contributing to the body weight reduction as well as to the improvement of the cardiometabolic risk related to obesity.

Topics: Anti-Obesity Agents; Cyclobutanes; Humans; Lactones; Life Style; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Safety; Treatment Outcome; Weight Loss

To assist health professionals who counsel patients with overweight and obesity, a systematic review was undertaken to determine types of weight-loss interventions that contribute to successful outcomes and to define expected weight-loss outcomes from such interventions.. A search was conducted for weight-loss-focused randomized clinical trials with >or=1-year follow-up. Eighty studies were identified and are included in the evidence table.. The primary outcomes were a measure of weight loss at 6, 12, 24, 36, and 48 months. Eight types of weight-loss interventions-diet alone, diet and exercise, exercise alone, meal replacements, very-low-energy diets, weight-loss medications (orlistat and sibutramine), and advice alone-were identified. By using simple pooling across studies, subjects mean amount of weight loss at each time point for each intervention was determined.. Efficacy outcomes were calculated by meta-analysis and provide support for the pooled data. Hedges' gu was combined across studies to obtain an average effect size (and confidence level).. A mean weight loss of 5 to 8.5 kg (5% to 9%) was observed during the first 6 months from interventions involving a reduced-energy diet and/or weight-loss medications with weight plateaus at approximately 6 months. In studies extending to 48 months, a mean 3 to 6 kg (3% to 6%) of weight loss was maintained with none of the groups experiencing weight regain to baseline. In contrast, advice-only and exercise-alone groups experienced minimal weight loss at any time point.. Weight-loss interventions utilizing a reduced-energy diet and exercise are associated with moderate weight loss at 6 months. Although there is some regain of weight, weight loss can be maintained. The addition of weight-loss medications somewhat enhances weight-loss maintenance.

Topics: Adult; Anti-Obesity Agents; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Exercise; Female; Follow-Up Studies; Food, Formulated; Humans; Lactones; Longitudinal Studies; Male; Obesity; Orlistat; Treatment Outcome; Weight Loss

This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Cyclobutanes; Humans; Lactones; Neurotransmitter Agents; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Treatment Outcome

Topics: Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Body Mass Index; Cyclobutanes; Diagnosis, Differential; Enzyme Inhibitors; Humans; Lactones; Male; Middle Aged; Obesity; Obesity, Morbid; Orlistat; Overweight; Piperidines; Prognosis; Pyrazoles; Rimonabant; Time Factors; Weight Loss

The obesity pandemic will likely have a significant impact on the global incidence of cardiovascular disease. Although the mechanisms linking obesity and cardiovascular disease are unclear, recent studies have implicated the adipocyte as a potentially important mediator of vascular complications. The adipocyte is no longer considered a passive storage depot for triglycerides and fatty acids, but rather an active metabolic organ capable of producing several factors, commonly referred to as adipokines, that may have effects on many physiological and pathophysiological processes. With increasing fat mass, several adipose-related factors are upregulated that may affect local and distant inflammatory processes, including atherothrombosis. Other factors, such as adiponectin, are downregulated with increasing fat mass. Although most adipokines are thought to promote vascular disease, several studies over the past few years indicate adiponectin is actually protective against both diabetes and vascular disease. There are now available pharmacologic agents capable of altering the adipocyte transcription profile. This review will focus on the potential impact of adipocyte-derived factors towards vascular disease and emerging therapeutic strategies that may alter these effects.

Topics: Adiponectin; Anti-Obesity Agents; Cardiovascular Diseases; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypertension; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Risk Factors

Obesity is a chronic metabolic disorder that affects one third of American adults. Modest weight losses of just 5% to 10% of body weight, which are achievable with lifestyle modification and pharmacotherapy, can lead to remarkable improvements in many obesity-associated co-morbidities, including dyslipidemia, hypertension, and type 2 diabetes. In this review, the indications for pharmacotherapy and the goals of treatment are discussed, and current and future pharmacologic approaches to the treatment of obesity are examined. Current pharmacologic therapies for obesity are limited, but recent advances in our understanding of the complex and overlapping endocrine pathways that regulate body weight have led to new opportunities for antiobesity drug development. Important drug targets that are highlighted in this review include adipocyte-derived hormones, hypothalamic neuropeptides, and gastrointestinal hormones.

Topics: Amyloid; Anti-Obesity Agents; Appetite Depressants; Body Weight; Chronic Disease; Comorbidity; Cyclobutanes; Exenatide; Gastrointestinal Hormones; Humans; Islet Amyloid Polypeptide; Lactones; Leptin; Metformin; Obesity; Orlistat; Peptides; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Venoms

The current obesity pandemic imposes a major global disease burden. However, sustained weight loss of between 5 and 10% in the obese confers marked health benefits. Currently available pharmacotherapies, orlistat and sibutramine, can induce weight loss of between 5 and 10% over 2 years or more. However, in these trials, drug induced weight loss tends to be only 2-4 kg greater than that produced by placebo control. Despite this, in the XENDOS trial, the modest placebo-subtract weight loss produced by orlistat (2.8 kg) reduced the incidence of diabetes by over a third. Recent data on the potential anti-obesity drug rimonabant are also reviewed.

Topics: Anti-Obesity Agents; Appetite Depressants; Cost of Illness; Cyclobutanes; Feeding Behavior; Humans; Lactones; Obesity; Orlistat; Treatment Outcome; Weight Loss

Acceptable adverse effects and a clinical relevant weight loss of 3 to 5 kilograms have been found in long-term randomized clinical trials for sibutramine (Reductil) and orlistat (Xenical); these drugs may be prescribed for treatment of obesity for a duration of one and four years, respectively. This also seems to be the case for rimonabant (Acomplia), which is expected to receive approval in 2005 or 2006. However, until data on morbidity and mortality are available from RCTs, there is no absolute indication for prescribing drugs for treatment of obesity.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diethylpropion; Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Time Factors; Weight Loss

Obesity is strongly associated with conditions such as hypertension, diabetes mellitus and osteoarthritis that have known adverse health outcomes. The rising prevalence of obesity threatens to overburden our health care system. As a result, the need for safe and effective treatment options is urgent. Unfortunately, pharmacologic treatment options have been disappointing either because of poor side effect profiles or limited long-term efficacy. Our goal is to review currently available pharmacologic treatments and the data supporting their use so that practicing physicians may better incorporate them into a comprehensive, long-term treatment strategy for their patients. We focus on orlistat and sibutramine as these are the two medicines approved by the FDA for long-term treatment of obesity. In addition, we review briefly agents approved for short-term use as well as agents such as zonisamide and topiramate which have shown some promise as weight loss agents in specific clinical circumstances. Finally, we highlight one medicine currently in phase III clinical trials, an endocannabinoid receptor antagonist. Given the overwhelming research focus on this disease, it is likely that the coming years will bring more treatment options, raising the chance that our patients will have meaningful and sustained weight loss.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Fructose; Humans; Isoxazoles; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Selective Serotonin Reuptake Inhibitors; Topiramate; Zonisamide

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. NAFLD has been associated with obesity and other features of the metabolic syndrome, including insulin resistance, impaired glucose tolerance, and dyslipidemia. As a result, and with a lack of other effective treatments, weight loss achieved through lifestyle modifications (diet and exercise) has been promoted as the standard treatment. However, there is very little empiric evidence to support the effectiveness of weight loss for NAFLD. This article reviews the current literature on the effects of weight loss achieved through lifestyle modification or medications on NAFLD. To date, there have been no randomized controlled trials of weight loss interventions on hepatic pathology. Only three published trials (N = 89 subjects), which include a comparison group, have been published. These studies suggest improvement in liver enzymes and/or hepatic pathology; however, direct between group comparisons are lacking. Four small, nonrandomized studies (N = 59 subjects) have evaluated the effect of weight loss achieved with medications (4 of orlistat, 1 of sibutramine) on NAFLD. These suggest some improvement in liver enzymes and histopathology. Finally, a brief review of observational studies on the association between NAFLD pathology or liver enzymes and diet composition suggests a possible role for the manipulation of macronutrients and/or micronutrients in NAFLD treatment. In summary, there is little empiric evidence to support the role of weight loss achieved through lifestyle modification or medication in the treatment of NAFLD. Rigorously conducted, randomized controlled trials are needed in this area.

Topics: Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Chronic Disease; Cyclobutanes; Diet, Reducing; Disease Progression; Fatty Liver; Humans; Lactones; Life Style; Orlistat; Weight Loss

Currently, the substances orlistat and sibutramine are approved drugs for the pharmacotherapy of obesity. Used in combination with increased exercise and dietary measures, both are capable of significantly reducing weight. In the USA and Europe, official approval for the selective cannabinoid receptor antagonist, rimonabant has been applied for.

Topics: Anti-Obesity Agents; Appetite Depressants; Cannabinoid Receptor Antagonists; Clinical Trials as Topic; Cyclobutanes; Enzyme Inhibitors; Exercise; Humans; Lactones; Lipase; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Time Factors; Weight Loss

Obesity has reached global epidemic proportions because of an increasingly obesogenic environment. This review examines the association between obesity, and in particular visceral fat, as a risk factor for cardiovascular disease and mortality.. The World Health Organization defines obesity based on the body mass index. Recently the waist-to-hip ratio has been shown to be a significantly stronger predictor of cardiovascular events than body mass index. The metabolic syndrome and its evolving definition represent a cluster of metabolic risk factors which help predict cardiovascular disease and mortality. Although insulin resistance plays a central role in the pathophysiology of the metabolic syndrome, there is limited support for therapy with insulin sensitizers, thiazolidinediones, in patients with coronary artery disease. The current anti-obesity drugs, orlistat and sibutramine, have only a modest effect on weight loss. The blockade of the endocannabinoid system with rimonabant, however, may be a promising new strategy.. Obesity is associated with significant increase in cardiovascular risk. Lifestyle modification remains the cornerstone of management although anti-obesity medications may be indicated in high risk individuals with comorbid disease.

Topics: Appetite Depressants; Body Fat Distribution; Body Mass Index; Cardiovascular Diseases; Cyclobutanes; Humans; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Lactones; Life Style; Lipid Metabolism; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Thiazolidinediones; Waist-Hip Ratio

This review offers an overview of physiological agents, current therapeutics, as well as medications, which have been extensively used and those agents not currently available or non-classically considered anti-obesity drugs. As obesity - particularly that of central distribution - represents an important triggering factor for insulin resistance, its pharmacological treatment is relevant in the context of metabolic syndrome control. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral energy homeostasis (nutrients, monoamines, and peptides), on beta-phenethylamine pharmacological derivative agents (fenfluramine, dexfenfluramine, phentermine and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrin, phenylpropanolamine), phenylpropanolamine oxytrifluorphenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials - over ten-week long - is also presented for medications used in the management of obesity, as well as data about future medications, such as a the inverse cannabinoid agonist, rimonabant.

Topics: Amphetamines; Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Energy Metabolism; Homeostasis; Humans; Lactones; Mazindol; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Weight Loss

Obesity is a chronic disease requiring a similar long term approach to management as that of other chronic conditions.. This article discusses the role of medications in the overall management of obesity.. Management needs to be multifaceted, aiming to alter the patient and family micro-environment to one favouring better weight control through sustainable behavioural changes to physical activity and diet. Weight loss medications may provide additional benefit. Currently we have only two medications suitable for long term therapy--orlistat and sibutramine. Sibutramine, which acts centrally to suppress appetite, has shown efficacy for up to 2 years. Orlistat, a lipase inhibitor, reduces fat absorption and has been shown to reduce and maintain weight for up to 4 years. The effect of these medications is modest, generally providing less than 5 kg weight loss when compared with placebo. Patients need to have realistic expectations and understand the benefits of sustained modest weight loss. It is important that weight loss medications are prescribed in combination with lifestyle modification.

Topics: Anti-Obesity Agents; Chronic Disease; Cyclobutanes; Diethylpropion; Humans; Lactones; Obesity; Orlistat; Phentermine; Weight Loss

The global obesity epidemic is causing much concern among health professionals due to the major health risks associated with obesity. Excess weight, particularly abdominal obesity, elevates multiple cardiovascular and metabolic risk factors, including Type 2 diabetes, hypertension, dyslipidaemia and cardiovascular disease. Thus obesity management goals should encompass health improvement and cardiometabolic risk reduction as well as weight loss. While lifestyle and diet modification form the basis of all effective strategies for weight reduction, some individuals may need additional intervention. About one in four people with BMI >27 kg/m(2) (those who have weight-related morbidity and who have been unsuccessful losing weight in standard ways) may require adjunctive therapy such as pharmacotherapy, very low energy diets/meal replacements, or bariatric surgery. This review focuses on appropriate use of pharmacotherapy for obesity and cardiometabolic risk. Sibutramine and orlistat are currently available for use in Australia. Rimonabant has been approved for use in the European Union, and is being considered for regulatory approval in the USA and Australia. The efficacy and safety of these three agents are examined. In addition, several novel pharmacotherapy agents in development are discussed.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Risk Factors; Safety; Treatment Outcome

Intervention in weight management should begin before the onset of the metabolic syndrome. Therapeutic lifestyle changes (e.g., diet and physical activity) comprise the cornerstone of care for overweight and obese patients. Behavior modification approaches are useful in facilitating adherence to specific dietary regimens. Pharmacotherapy is an option for patients with a BMI >30 kg/m(2) or for those with a BMI of 27 to 30 kg/m(2) and two or more risk factors, who have failed on diet and exercise alone. To date, the U.S. Food and Drug Administration has approved three weight loss agents: sibutramine, orlistat, and phentermine.

Topics: Caloric Restriction; Cardiovascular Diseases; Cyclobutanes; Diabetes Mellitus; Diet; Diet, Fat-Restricted; Diet, Mediterranean; Exercise; Feeding Behavior; Food, Formulated; Humans; Lactones; Metabolic Syndrome; Obesity; Orlistat; Phentermine; Prediabetic State; Risk Reduction Behavior; Weight Loss

Obesity has been described as the greatest current threat to human health. Although diet and lifestyle changes remain the cornerstones of therapy for obesity, weight losses are often small, and long-term success is disappointing.. When these lifestyle-modifying attempts fail, the use of anti-obesity drugs is warranted. 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 body weight loss. The currently available drugs, sibutramine and orlistat, appear modestly effective in promoting weight loss. However, pharmacological therapy for obesity is in transition; expanding knowledge of the physiological mechanisms of body weight regulation has revealed new molecular targets, and more than 150 novel agents are under active development.. Because weight regulation is complex, and redundant systems protect against perceived starvation, optimal treatment of obesity will likely require combinations of therapies. In addition, a better comprehension of the problem prior to its treatment would be preferable before targeting homeostatic pathways which could be irrelevant.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Models, Biological; Obesity; Orlistat; Weight Loss

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Cyclobutanes; Drug Therapy, Combination; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Weight Loss

In recent years, obesity has become a major public health problem in Western countries. The World Health Organization has defined obesity as a global epidemic of the third millennium. Treatment options for weight management include dietary intervention, physical activity, behavior modification, pharmacotherapy and surgery. However, the complexity of this chronic condition necessitates a coordinated multidisciplinary team-approach to the care of obese patients who fail weight control. The long-term duration of the treatment and the necessity of monitoring compliance and effectiveness should be considered. The objective of this article was to review the major controlled randomized clinical trials dealing with the different medical strategies for weight loss and its maintenance in overweight and obese patients.

Topics: Anti-Obesity Agents; Appetite Depressants; Behavior Therapy; Body Mass Index; Cyclobutanes; Exercise; Follow-Up Studies; Humans; Lactones; Life Style; Obesity; Orlistat; Overweight; Patient Compliance; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Weight Loss

Topics: Adolescent; Appetite Depressants; Body Mass Index; Clinical Trials as Topic; Cyclobutanes; Female; Humans; Lactones; Male; Mexico; Obesity; Orlistat; United States

Obesity has become a significant health problem in industrialised and developing countries, and despite all nutritional and behavioural approaches, its prevalence is still increasing. In recent years, the identification and characterisation of central and peripheral mechanisms involved in the regulation of energy balance has made remarkable progress and provided numerous targets for novel anti-obesity agents. However, only few anti-obesity drugs are on the market and not many compounds have entered clinical development. In the present review, the clinically available agents are discussed and their pharmacological profiles are compared. Some of the drugs that are currently in clinical development are mentioned as examples of the possible future range of anti-obesity agents. Selected topics in drug discovery are presented to illustrate novel targets and concepts for the pharmacotherapy of obesity.

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Cyclobutanes; Drug Design; Energy Metabolism; Homeostasis; Humans; Lactones; Life Style; Models, Biological; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Technology, Pharmaceutical

Long-term success in obesity therapy is difficult to obtain, therefore drug therapy appears to be helpful. Until today, end-point studies for obesity drugs beyond the improvement of individual surrogate parameters are still missing. For all available drugs, medical treatment can be recommended only for a limited period of time due to the data of the studies and under consideration of side effects. Although a weight reduction leads to an improvement of cardiovascular risk factors and hence a reduction of cardiovascular morbidity and mortality should be expected, no study could prove it so far. Despite the positive influence on individual surrogate parameters, the use of the present available therapies appears underwhelming. In this overview the approved substances and perspectives of new therapeutic concepts are represented.

Topics: Anti-Obesity Agents; Anticonvulsants; Cyclobutanes; Fructose; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Topiramate

Obesity is closely related to type 2 diabetes and long-term weight reduction is an important part of the care delivered to obese persons with diabetes.. To assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes.. Computerized searches were performed of MEDLINE (January 1966 to May 2004), EMBASE (January 1974 to May 2004, Web of Science (January 1981 to May 2004, and other electronic bibliographic databases, supplemented with hand searches of reference lists and selected journals.. Randomized, controlled trials were included where pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished literature in any language and with any study design was included.. Two reviewers abstracted data and the quality of included studies was evaluated by assessing potential attrition, as well as selection and measurement bias, and a Jadad score was obtained. Effects were combined using a random effects model.. A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 - 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 - 2.8) at 12 to 57 weeks follow-up, and sibutramine 5.1 kg (CI, 3.2 - 7.0) at 12 to 52 weeks follow-up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudophedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine.. Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Fluoxetine; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Carol McLoughlin looks at the advantages and drawbacks of using drugs to treat obesity and describes new areas of research that may offer new solutions to tackling this rapidly growing health and medical problem.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Leptin; Obesity; Orlistat

The association between obesity and hypertension is well known. The hemodynamic features of obesity-related hypertension are an expansion of extracellular volume inducing hypervolaemia and increased cardiac output, with activation of both the sympathetic nervous system and the renin--angiotensin system. It is suggested that obesity-related hypertension may be considered as a subset of essential hypertension, and treated as an identity. Orlistat and sibutramine both reduce body weight in the obese patients. The use of orlistat in obese hypertensive patients is associated with a small decrease in blood pressure, whereas sibutramine may increase the blood pressure. Thus, orlistat may be preferred in the obese hypertensive patients. Diuretics and beta-blockers decrease insulin sensitivity, which is an unwanted effect in obesity, and should be used with caution in obese hypertensive patients. The calcium channel blockers have no or minor effects on insulin sensitivity and may be considered for use in obese hypertensive patients. Inhibitors of the effects of angiotensin may be the antihypertensive drugs of choice for obese hypertensive patients, as in addition to reducing blood pressure, ACE inhibitors and AT(1) receptor antagonists have no effect or improve insulin sensitivity, and are renoprotective. More clinical trials are needed for the centrally acting antihypertensives (clonidine, rilmenidine) in obese hypertensive patients, as they inhibit the sympathetic nervous and renin--angiotensin systems, which are overactive in this population.

Topics: Anti-Obesity Agents; Antihypertensive Agents; Appetite Depressants; Cyclobutanes; Humans; Hypertension; Insulin; Lactones; Lipids; Obesity; Orlistat

The increase in obesity prevalence is problematic as this condition is associated with health complications such as diabetes and cardiovascular diseases, more particularly when the excess body fat is stored in the deep abdominal region. The mainstay of therapy consists of behavior modification related to obesity such as overeating and physical inactivity. When these lifestyle modifying attempts fail, the use of anti-obesity drugs is warranted. 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 body weight loss. The currently available drugs, sibutramine and orlistat, appear modestly effective in promoting weight loss. Ongoing studies continue to evaluate other drug treatments that may result in body weight reduction through a number of different mechanisms. Thus, the aim of this review is to present an overview of the current drugs available (particularly sibutramine and orlistat) as well as potential future candidates, and the impact of these agents on obesity and cardiovascular physiology. Furthermore, the therapeutic paradox of sibutramine in preventing obesity will be discussed as well as the beneficial impact of physical exercise on cardiac economy.

Topics: Animals; Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Clinical Trials as Topic; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Risk Factors

Topics: Adult; Appetite Depressants; Cyclobutanes; Diethylpropion; Fluoxetine; Gastric Bypass; Gastroplasty; Humans; Lactones; Mazindol; Obesity; Orlistat; Phentermine

The prevalence of child and adolescent overweight and obesity is rapidly increasing and is associated with morbidity, both medical and psychosocial. Obesity is unlikely to resolve spontaneously. It is important that health professionals can assess obesity and initiate an action plan. The evidence base for what works best in the management of child and adolescent overweight and obesity is limited. It is uncertain whether protocols from clinical research trials can be translated into primary care. Dietary change, with an emphasis on lower fat intake and smaller portion size, should be commenced. There should be an increase in physical activity and a decrease in sedentary behaviours, combined with behavioural change and parental involvement. These are the elements of a lifestyle intervention. In the severely obese adolescent with obesity-related co-morbidity, the use of very low-energy diets and anti-obesity agents could be considered. Bariatric surgery may be indicated in carefully selected, older, severely obese adolescents.

Topics: Adolescent; Anti-Obesity Agents; Behavior Therapy; Child; Child Behavior; Cyclobutanes; Diet, Reducing; Dietary Fats; Humans; Lactones; Motor Activity; Obesity; Orlistat; Parents

Obesity guidelines state that pharmacologic therapy can be considered if a patient fails to lose 10 percent of their original body weight after 6 months of adhering to a low calorie diet, exercise, and behavior modification. Many published trials have shown sibutramine and orlistat to be effective for weight loss and weight maintenance when used with lifestyle modifications. However, few trials have studied the efficacy and safety of these medications in the elderly. This article provides a review of the FDA approved medications currently available for the treatment of obesity. Pertinent clinical trials are also reviewed and recommendations regarding the use of these agents in the elderly are discussed.

Topics: Aged; Amphetamines; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

To update physicians, especially paediatricians, in the rapidly developing field of pharmacotherapy of childhood and adolescent obesity.. The paper reviews current and investigational antiobesity drugs.. At present, there are only few drugs approved by the Food and Drug Administration (FDA) for the treatment of adult obesity. The most important ones are sibutramine and orlistat. The FDA in the USA approved the latter drug in 2003, and it has recently been approved by the European Union for the treatment of adolescents. There are several investigational antiobesity agents but only few new and promising substances like Rimonabant (a cannabinoid receptor antagonist) and axokine (ciliary neutrotrophic factor) are already at an advanced stage of development.. In adults, it seems to be justified using drugs for long-term treatment of 'medically important' obesity. Strict guidelines concerning the treatment of obese adolescents with orlistat are needed. It is only hoped that double-blind placebo-controlled studies investigating the new and promising drugs will also include adolescents and provide sufficient scientific data to get them licensed for the treatment of obese adolescents.

Topics: Adolescent; Anti-Obesity Agents; Appetite Depressants; Child; Cyclobutanes; Drugs, Investigational; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat

Cardiovascular disease (CVD) is the leading cause of death of men and women in the United States. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing CVD and metabolic disease. Because visceral adipose tissue uniquely contributes to the pathophysiology of CVD and insulin resistance, waist circumference is now being considered as a more useful marker of potential health risks associated with overweight and obesity than body mass index. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, thereby reducing the risk of developing chronic disease and CVD.

Topics: Anti-Obesity Agents; Coronary Disease; Cyclobutanes; Exercise; Feeding Behavior; Humans; Intra-Abdominal Fat; Lactones; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant

Obesity is a chronic medical disorder that is not going away anytime soon. Physicians need all the education, tools, and resources possible to successfully help their overweight and obese patients. Weight-loss medications alone are clearly not the answer. However, they are one tool physicians can use in combination with lifestyle changes to increase the success of long-term weight loss in selected patients.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Life Style; Obesity; Orlistat; Patient Compliance; Treatment Outcome; Weight Loss

To undertake a systematic review of the long-term effects of obesity treatments on body weight, risk factors for disease, and disease.. The study encompassed three systematic reviews that examined different aspects of obesity treatments. (1) A systematic review of obesity treatments in adults where the methods of the Cochrane Collaboration were applied and randomised controlled trials (RCTs) with a follow-up of at least 1 year were evaluated. (2) A systematic epidemiological review, where studies were sought on long-term effects of weight loss on morbidity and/or mortality, and examined through epidemiological modelling. (3) A systematic economic review that sought reports with both costs and outcomes of treatment, including recent reports that assessed the cost-effectiveness of pharmaceutical and surgical interventions. A Markov model was also adopted to examine the cost-effectiveness of a low-fat diet and exercise intervention in adults with obesity and impaired glucose tolerance.. The addition of the drugs orlistat or sibutramine was associated with weight loss and generally improved risk factors, apart from diastolic blood pressure for sibutramine. Metformin was associated with decreased mortality after 10 years in obese people with type 2 diabetes. Low-fat diets were associated with continuing weight loss for 3 years and improvements in risk factors, as well as prevention of type 2 diabetes and improved control of hypertension. Insufficient evidence was available to demonstrate the benefits of low calorie or very low calorie diets. The addition of an exercise or behaviour programme to diet was associated with improved weight loss and risk factors for at least 1 year. Studies combining low-fat diets, exercise and behaviour therapy suggested improved hypertension and cardiovascular disease. Family therapy was associated with improved weight loss for 2 years compared to individual therapy. There was insufficient evidence to conclude that individual therapy was more beneficial than group therapy. Weight lost more quickly (within 1 year), from the epidemiology review, may be more beneficial with respect to the risk of mortality. The effects of intentional weight loss need further investigation. Weight loss from surgical and non-surgical interventions for people suffering from obesity was associated with decreased risk of development of diabetes, and a reduction in low-density lipoprotein cholesterol, total cholesterol and blood pressure, in the long term. Targeting high-risk individuals with drugs or surgery was likely to result in a cost per additional life-year or quality-adjusted life-year (QALY) of no more than 13,000 British pounds. There was also suggestive evidence of cost saving from treatment of people with type 2 diabetes with metformin. Targeting surgery on people with severe obesity and impaired glucose tolerance was likely to be more cost-effective at 2329 British pounds per additional life-year. Economic modelling over 6 years for diet and exercise for people with impaired glucose tolerance was associated with a high initial cost per additional QALY, but by the sixth year the cost per QALY was 13,389 British pounds. Results did not include cost savings from diseases other than diabetes, and therefore may be conservative.. The drugs orlistat and sibutramine appear beneficial for the treatment of adults with obesity, and metformin for obese patients with type 2 diabetes. Exercise and/or behaviour therapy appear to improve weight loss when added to diet. Low-fat diets with exercise, or with exercise and behaviour therapy are associated with the prevention of type 2 diabetes and hypertension. Long-term weight loss in epidemiological studies was associated with reduced risk of type 2 diabetes, and may be beneficial for cardiovascular disease. Low-fat diets and exercise interventions in individuals at risk of obesity-related illness are of comparable cost to drug treatments. Long-term pragmatic RCTs of obesity treatments in populations with obesity-related illness or at high risk of developing such illness are needed (to include an evaluation of risk factors, morbidity, quality of life and economic evaluations). Drug trials that include dietary advice, plus exercise and/or behaviour therapy are also needed. Research exploring effective types of exercise, diet or behaviour and also interventions to prevent obesity in adults is required.

Topics: Anti-Obesity Agents; Behavior Therapy; Caloric Restriction; Cost-Benefit Analysis; Cyclobutanes; Diet, Fat-Restricted; Humans; Hypoglycemic Agents; Lactones; Markov Chains; Metformin; Obesity; Orlistat; Physical Fitness; Randomized Controlled Trials as Topic; Risk Factors

Obesity is closely related to type 2 diabetes mellitus, and weight reduction is an important part of the care delivered to obese persons with diabetes. The objective of this review was to assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes.. A systematic review of the literature was performed, and studies were included if pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished studies with any design were included. A random effects model was used to combine outcomes from randomized controlled trials.. Sufficient data for the meta-analysis were available for fluoxetine, orlistat, and sibutramine. Fourteen randomized, placebo-controlled trials were included in the review, with a total of 2231 patients. Pharmacotherapy produced modest reductions in weight for fluoxetine (3.4 kg [95% confidence interval (CI), 1.7-5.2 kg] at 8-16 weeks of follow-up; 5.1 kg [95% CI, 3.3-6.9 kg] at 24-30 weeks; and 5.8 kg [ 95% CI, 0.8-10.8 kg] at 52 weeks); orlistat (2.6 kg [95% CI, 2.1-3.2 kg] [2.6% loss] at 52 weeks); and sibutramine (4.5 kg [95% CI, 1.8-7.2 kg] [3.3% loss] at up to 26 weeks). Glycated hemoglobin was also modestly reduced: fluoxetine (1.0% [95% CI, 0.4%-1.5%] at 8-16 weeks; 1.0% [95% 0.6%-1.4%] at 24-30 weeks; and 1.8% [95% CI, -0.2%-3.8%] at 52 weeks); orlistat (0.4% [95% CI, 0.3%-0.5%]); and sibutramine (0.7% [95% CI, -0.5%-1.9%]). Gastrointestinal adverse effects were common with orlistat; tremor, somnolence, and sweating with fluoxetine; and palpitations with sibutramine.. Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 26 to 52 weeks. However, the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear. Interventions that combine pharmacologic therapy with intensive behavioral interventions may be more effective but need additional research.

Topics: Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Drug Therapy; Female; Fluoxetine; Humans; Lactones; Male; Meta-Analysis as Topic; Middle Aged; Orlistat; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Weight Loss

Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established.. To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration.. MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed.. Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included.. Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss.. Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate.. Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Weight; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Obesity is a chronic disease with a worldwide increasing incidence. The mainstay of therapy consists in modification of behaviour related to obesity such as overeating and physical inactivity. When these life-style modifying attempts fail, the use of anti-obesity drugs is warranted. The two available drugs, orlistat and sibutramine, are capable of reducing body weight by 10%. Failure of these medications in a subset of patients to achieve adequate weight loss and limited overall efficacy have led to an extensive research on novel anti-obesity agents. This review presents an overview on the current drugs available as well as on potential future candidates.

Topics: Appetite Depressants; Body Weight; Clinical Trials as Topic; Cyclobutanes; Diabetes Mellitus; Humans; Lactones; Obesity; Orlistat; Satiety Response; Treatment Outcome

The current obesity pandemic imposes a major global disease burden. Levels of non-communicable diseases such as type 2 diabetes, cardiovascular disease and some cancers will continue to rise unless an effective approach to treat obesity is found. Sustained weight loss of between 5-10% in the obese, by various means, confers marked health benefits. The currently available pharmacotherapies, orlistat and sibutramine, can induce weight loss of between 5-10% over 2 years or more. In trials, orlistat and sibutramine induced weight loss tends to be only between 2-4 kg greater than that produced by placebo control. However, this additional placebo subtracted weight loss produces marked additional improvements in diabetes and cardiovascular risk factors. Moreover, in the 4 year long XENDOS trial, the modest placebo subtracted weight loss produced by orlistat (2.8 kg) reduced the incidence of diabetes by over a third in those with normal glucose tolerance, and by nearly half in those with impaired glucose tolerance. Despite this, prescription sales of sibutramine in the US have apparently remained static and those of orlistat have fallen, with the drug now entering the global over-the-counter medication market. Recent data on potential anti-obesity drugs currently under going phase III trials, such as Rimonabant and Topiramate, demonstrate these drugs produce greater and more prolonged weight loss. Wider use of pharmacotherapy and enhanced efficacy for the next generation of anti-obesity drugs certainly promise to reduce obesity related illness if not halt the rise in obesity per se.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Energy Metabolism; Feeding Behavior; Fructose; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Topiramate

Topics: Adult; Appetite Depressants; Bupropion; Cyclobutanes; Diethylpropion; Fluoxetine; Fructose; Gastric Bypass; Gastroplasty; Humans; Lactones; Lipase; Obesity; Orlistat; Phentermine; Topiramate

The prevalence in obesity has increased dramatically over the past 30 years, more than double in the United States alone. Obesity is associated with an increased risk for type 2 diabetes mellitus, dyslipidemia, hypertension, biliary disease, obstructive sleep apnea, and certain types of cancer. The pathophysiology of obesity is complex, involving behavioral, environmental, and genetic factors. Current treatment options include behavior modification and lifestyle changes which incorporate weight-reducing diets and physical activity, FDA approved long-term anti-obesity pharmacological agents sibutramine and orlistat, non-FDA approved over-the-counter (OTC) supplements and nutriceuticals, and, when appropriate, bariatric surgery. Without adequate prevention and treatment of obesity, government agencies have suggested that the direct and indirect costs associated with obesity may overwhelm the healthcare system. This brief review explores the current data available on treatments for the obese patient including the relative merits of different types of macronutrient composition (e.g., low carbohydrate vs. high carbohydrate diets) of weight-reducing diets, the value of resistance/ strength training in physical activity programs designed for the obese patient, the safety and efficacy associated with OTC supplements and nutriceuticals for weight reduction (e.g., Ephedra, conjugated linoleic acid (CLA), Garcinia cambogia/ hydroxycitric acid (HCA), chromium, pyruvate), the safety and efficacy of FDA-approved long-term obesity treatments sibutramine and orlistat, and bariatric surgery.

Topics: Anti-Obesity Agents; Bariatrics; Chromium; Citrates; Cyclobutanes; Energy Intake; Ephedrine; Exercise Therapy; Garcinia cambogia; Herbal Medicine; Humans; Lactones; Linoleic Acids, Conjugated; Obesity; Orlistat; Phytotherapy; Pyruvic Acid

Topics: Amylases; Androgens; Anti-Obesity Agents; Citrates; Cyclobutanes; Dietary Fats; Fat Substitutes; Fatty Acids; Glucagon; Glucagon-Like Peptide 1; Glucosidases; Human Growth Hormone; Humans; Intestinal Absorption; Lactones; Lipase; Obesity; Orlistat; Peptide Fragments; Protein Precursors; Sucrose

Topics: Appetite Depressants; Body Mass Index; Cyclobutanes; Exercise; Female; Humans; Lactones; Obesity; Orlistat; Women's Health

Topics: Adult; Appetite Depressants; Cyclobutanes; Diethylpropion; Fluoxetine; Humans; Lactones; Mazindol; Obesity; Orlistat; Phentermine; Phenylpropanolamine; Selective Serotonin Reuptake Inhibitors

Obese patients unable to achieve significant weight loss with lifestyle changes alone may require drug therapy, and such therapy may be needed long term lest weight lost be regained. In the United States, only sibutramine and orlistat are available for the long-term treatment of obesity. Clinical trials have shown that both drugs can induce and maintain weight loss, even in patients with comorbid conditions such as hypertension or type 2 diabetes. Their use must be combined with behavior modification and a structured meal plan, however, for patients to reap the full benefits of such treatment.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Obesity is the most important modifiable risk factor for type 2 diabetes mellitus and most patients with diabetes are overweight or obese. It is well known that excess bodyweight induces or aggravates insulin resistance, which is a characteristic feature of type 2 diabetes. Thus, bodyweight plays a central role in the prevention and treatment of diabetes. Recent data suggest that lifestyle intervention in patients with impaired glucose tolerance results in an impressive reduction in the conversion to overt diabetes, which is greater than the effect of early intervention with drugs such as metformin or acarbose. The prevention of diabetes has been shown to be associated with the extent of weight loss. In patients with type 2 diabetes, weight loss by any means is followed by an improvement of metabolic control and associated risk factors. The most appropriate recommendation for obese patients with type 2 diabetes is a nutritionally balanced, moderately hypocaloric diet with a reduced intake of saturated fat and an increase in physical activity. If this standard approach is only partly successful or not at all, additional strategies such as weight-lowering drugs, very low-calorie diets for limited periods of up to 12 weeks, and, for severely obese patients, bariatric surgery should be carefully considered. A large body of data suggests that such measures can be very effective in this patient group by improving metabolic disturbances and blood pressure. However, it is extremely important for the long-term outcome that the treatment is tailored to the needs and wishes of the individual patient. There is growing agreement that due to the low success rate of conventional therapies and the overwhelming benefit from weight loss, more determined and aggressive strategies may be appropriate to achieve the central goal of weight reduction in obese patients with type 2 diabetes.

Topics: Anti-Obesity Agents; Appetite Depressants; Blood Glucose; Cyclobutanes; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Gastric Bypass; Humans; Hypoglycemic Agents; Lactones; Obesity; Orlistat; Weight Loss

Chronic obesity is associated with various cardiovascular disorders, including diabetes, dyslipidemia, and hypertension. Pharmacotherapy with antiobesity agents is an important management strategy in conjunction with lifestyle interventions.. This article describes the pharmacologic management of obesity, concentrating on orlistat and sibutramine.. Relevant articles were identified through a MEDLINE search (1966-February 2002) using the terms obesity, overweight, weight loss, antiobesity drugs, orlistat, and sibutramine. The search for efficacy trials was limited to randomized controlled studies of >6 months' duration. Also included in the review were relevant references cited in the bibliographies of identified articles, news reports, and the authors' own data.. Orlistat reduces fat absorption by inhibiting gastrointestinal lipases. In randomized, controlled trials of up to 2 years' duration, orlistat plus a hypocaloric diet produced significantly greater weight loss than placebo (P < 0.001). In the maintenance phase, patients taking orlistat had less weight regain than did placebo recipients. The weight reduction with orlistat was also associated with a significant improvement in control of cardiovascular risk factors (P < 0.05). Unlike orlistat, sibutramine works by suppressing appetite; its efficacy, however, was similar to that of orlistat in the identified clinical trials. Orlistat was associated primarily with gastrointestinal side effects. Use of orlistat was associated with minimal drug interactions, except with cyclosporine, with which it should not be taken. Sibutramine was also well tolerated, although it may cause dry mouth, anorexia, and insomnia, and should be used with caution in patients at risk for cardiovascular disease.. Orlistat and sibutramine demonstrated a favorable efficacy and safety profile in randomized controlled trials. Current evidence supports their use as adjuncts to lifestyle modifications in the treatment of obesity.

Topics: Anti-Obesity Agents; Body Mass Index; Cyclobutanes; Dose-Response Relationship, Drug; Drug Interactions; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Topics: Anti-Obesity Agents; Cyclobutanes; Diabetes Mellitus, Type 2; Diet; Exercise; Humans; Lactones; Life Style; Obesity; Orlistat

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.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Clinical Trials as Topic; Combined Modality Therapy; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Practice Guidelines as Topic; Treatment Outcome

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Endocrinology; Humans; Lactones; Obesity; Orlistat

Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens.. To review systematically the long-term efficacy and safety of approved antiobesity medications.. MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed.. Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion.. Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms.. A total of 11orlistat (n=6021) and three sibutramine (n=929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3-3.1 kg) or 2.9% (95% CI: 2.3-3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6-4.9 kg) or 4.6% (95% CI: 3.8-5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8-16%) higher with orlistat and 15% (95% CI: 4-27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate.. There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigorous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

Topics: Anti-Obesity Agents; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic

Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established.. To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration.. MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed.. Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included.. Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss.. Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate.. Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Weight; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

The basis for a therapeutic concept for obesity comprises specific measures aimed at changing inappropriate lifestyle habits (overeating, unsuitable diet, sedentary lifestyle) and psychological counseling (identification of bad eating habits, motivation, intensive coaching). Education by a physician on an individual or small-group basis, with emphasis on the practical implementation of fitness training (endurance and muscle building!), together with modification of the diet, has proved successful. In parallel with this, supportive anti-obesity medication makes a useful contribution to weight reduction and the control of risk factors. Evidence-based anti-obesity drugs such as sibutramine and orlistat facilitate the start of weight reduction, thus providing additional motivation of success, and support the long-term effect by stabilizing the weight loss. Health insurance carriers should, in future, selectively support evaluated and approved medication-based and non-medication-based weight-reduction programs, and reimburse the patient who has successfully participated in one.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Clinical Trials as Topic; Cyclobutanes; Exercise; Humans; Lactones; Life Style; Middle Aged; Nutritional Physiological Phenomena; Obesity; Orlistat; Placebos; Psychotherapy; Risk Factors; Weight Loss

Obesity is a chronic disease resulting from various genetic factors and environmental conditions (nutrition, sedentary life-style, psychological factors). The importance of prevention and therapy of obesity is emerging because of the high prevalence of metabolic complications. The first goal of any therapy must be a stabilisation of weight, followed by a reduction of body weight. Any intervention must be long-acting. Short-acting therapies (diets) result in a regain of body weight in over 90%. The most effective therapy is an integrative concept basing on: change of nutrition by reduction of fat and carbohydrate intake (daily deficit of 500-1000 kcal). psychotherapeutic approach, targeting a long-term change of eating-behaviour and life-style, avoiding guilt feelings. encouraging physical activity. Drugs (Orlistat, Sibutramin) may be helpful in selected cases as a part of a limited treatment, they do not replace changes in lifestyle. Surgical interventions (gastric banding, gastric bypass) can be considered in morbid obesity with the presence of metabolic complications, as they are the most effective way of weight reduction.

Topics: Behavior Therapy; Combined Modality Therapy; Cross-Sectional Studies; Cyclobutanes; Diet, Reducing; Exercise; Gastroplasty; Humans; Incidence; Lactones; Lipids; Obesity; Orlistat; Switzerland; Treatment Outcome

Obesity is a chronic, complex, multifactorial disorder with increasing prevalence in modern society. Lifestyle modification has had limited success in treating this disorder. Currently approved pharmacologic treatments for obesity include sibutramine and orlistat, which have been associated with significantly greater weight loss than that seen with dieting alone. In addition, a greater percentage of patients who receive medical treatment achieve weight losses of more than 5% to 10% of their initial body weight. This weight loss is associated with improvements in blood pressure, insulin sensitivity, and dyslipidemia. Multiple new therapies that target several different regulatory pathways are currently in clinical trials.

Topics: Anti-Obesity Agents; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Weight Loss

Topics: Adult; Appetite Depressants; Cyclobutanes; Diethylpropion; Fluoxetine; Humans; Lactones; Mazindol; Obesity; Orlistat; Phentermine; Phenylpropanolamine

Obesity is associated with considerable morbidity and decreased life expectancy. Weight gain is a commonly encountered problem associated with antipsychotic treatment. We reviewed the literature regarding the mechanisms of weight gain in response to these agents and eight substances implicated as potential obesity prevention or treatment: orlistat, sibutramine, fluoxetine, topiramate, amantadine, nizatidine and cimetidine, and metformin. Weight gain in response to antipsychotic treatment may be mediated through serotonergic, dopaminergic, adrenergic, cholinergic, histaminergic and glutaminergic receptors. Sex hormone dysregulation and altered insulin sensitivity have also been implicated. Two compounds, orlistat and sibutramine, have been shown to help prevent weight gain following a hypocaloric diet, but orlistat requires compliance with a fat-reduced diet, and sibutramine is unsuitable for patients taking serotonergic agents. The weight reducing effect of fluoxetine, even in conjunction with a hypocaloric diet, is only transient. Topiramate, amantadine and metformin may have adverse side-effects potentially outweighing the weight reducing potential. The effectiveness of cimetidine and nizatedine remains unclear. The hazards of these agents in a psychiatric population are discussed. It is concluded that the current evidence does not support the general use of pharmacological interventions for overweight patients treated with antipsychotic medication, although individually selected patients may benefit.

Topics: Amantadine; Antipsychotic Agents; Cimetidine; Cyclobutanes; Fluoxetine; Fructose; Humans; Lactones; Metformin; Nizatidine; Obesity; Orlistat; Topiramate; Weight Gain

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.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Chemotherapy, Adjuvant; Cyclobutanes; Feeding Behavior; Female; Fructose; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Topiramate

A variety of medications used to assist with weight loss have been implicated in the precipitation or induction of depressive symptoms and disorders. This is true of a large number of phenylethylamine agents possessing psychostimulant properties, non-phenylethylamine psychostimulants (e.g., caffeine) and the serotonergic agent, fenfluramine. There is, as yet, no substantial evidence linking the more modern weight loss drugs, sibutramine and orlistat, to the aetiology of major depression. Nevertheless, when these drugs are used, major depression will continue to be an important clinical consideration because of the elevated frequency with which major depression occurs in obese patients, the contribution that major depression may make to poor outcomes in non-pharmacological weight loss treatment and because of the interplay between symptoms of depression and weight loss treatment.

Topics: Anti-Obesity Agents; Appetite Depressants; Central Nervous System Stimulants; Cyclobutanes; Depressive Disorder; Feeding Behavior; Humans; Lactones; Orlistat; Serotonin Agents

Topics: Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Risk Factors

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.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; History, 20th Century; Humans; Lactones; Obesity; Orlistat; Weight Loss

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.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Life Style; Obesity; Orlistat; Weight Loss

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.

Topics: Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Humans; Lactones; Methylcellulose; Obesity; Orlistat; Phentermine

Obesity is a multi-factorial, chronic disorder that has reached epidemic proportions in most industrialized countries and is threatening to become a global epidemic. Obese patients are at a higher risk from coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, certain cancers, cerebrovascular accidents, osteoarthritis, restrictive pulmonary disease, and sleep apnea. Obesity is a particularly challenging clinical condition to treat, because of its complex pathophysiological basis. Indeed, body weight represents the integration of many biological and environmental components. Efforts to develop innovative anti-obesity drugs have been recently intensified. In broad terms, researchers use different distinct strategies: first, to reduce energy intake; second, to increase energy expenditure; third, to alter the partitioning of nutrients between fat and lean tissue. In the present review we concentrate on the first of these strategies, by underlining the new pharmacological tools which are presently studied.

Topics: Animals; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Drug Industry; Humans; Lactones; Obesity; Orlistat

Besides genetic predisposition, obesity is the most important risk factor for the development of type 2 diabetes mellitus. Even modest weight reduction can improve blood glucose control in overweight subjects. After failure of lifestyle modifications, antiobesity drugs such as orlistat, a potent and selective inhibitor of gastric and pancreatic lipases that reduces lipid intestinal absorption, or sibutramine, a noradrenaline and 5-hydroxytryptamine reuptake inhibitor that regulates food intake, may be considered to favour weight loss and/or weight maintenance. Several placebo-controlled studies have recently demonstrated that both drugs are able to promote weight loss in obese type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. The greater weight reduction as compared to placebo was associated with a significant reduction of glycated haemoglobin levels and/or of the doses of classical antihyperglycaemic agents, especially in good responders who lost at least 10% of initial body weight. In addition, vascular risk factors associated to insulin resistance were also reduced after weight loss. These antiobesity agents may also contribute to delay or prevent the progression from impaired glucose tolerance to overt type 2 diabetes in at risk obese individuals ("Xenical in the prevention of diabetes in obese subjects" trial). Large long-term prospective studies, such as the "Sibutramine cardiovascular and diabetes outcome study" should better determine the place of pharmacological anti-obesity strategy in the overall management of obese patients with impaired glucose tolerance or type 2 diabetes.

Topics: Anti-Obesity Agents; Appetite Depressants; Blood Glucose; Clinical Trials as Topic; Controlled Clinical Trials as Topic; Cyclobutanes; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat; Weight Loss

Weight-loss medications are currently recommended for use only as an adjunct to diet, exercise, and behavior modification. Little, however, is known about the benefits of combining behavioral and pharmacological therapies or about the mechanisms that would make these combined approaches more effective than either used alone. This article reviews the effects of adding pharmacotherapy (i.e., principally sibutramine and orlistat) to a modest program of lifestyle modification. Studies revealed that the addition of medication typically improved short- and long-term weight loss compared with lifestyle modification alone. The best results, however, were obtained when medications were combined with an intensive, group program of lifestyle modification. The two approaches may have additive effects; behavioral treatment seems to help obese individuals control the external (i.e., food-related) environment, whereas pharmacotherapy may control the internal environment by reducing hunger, cravings, or nutrient absorption. The article examines possible methods of sequencing behavioral and pharmacological therapies and offers suggestions for future research.

Topics: Anti-Obesity Agents; Appetite Depressants; Behavior Therapy; Combined Modality Therapy; Cyclobutanes; Diet; Exercise; Humans; Lactones; Life Style; Obesity; Orlistat; Weight Loss

Topics: Animals; Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat; Weight Loss

Recognition by the American Heart Association that obesity is a major modifiable risk factor for coronary heart disease has prompted health providers to take a more active role in obesity management. Obesity has long been known to accompany a host of chronic diseases, e.g., type II diabetes, hypertension, and dyslipidemia. We now recognize that obesity is itself a chronic disease with a complex etiology; like diabetes and hypertension, it is treatable with a similar chronic disease treatment model. Relatively modest weight loss confers disproportionate health benefits, improving a roster of risk factors. Diet, exercise, and behavior modification still compose the gold standard of treatment. If these measures fail, medication and surgery should be considered for appropriate patients. With current techniques, many patients can achieve realistic weight goals that can be maintained over the long term. Published management guidelines can now assist in integrating the practical applications of obesity-related research findings into everyday clinical practice.

Topics: Anti-Obesity Agents; Coronary Disease; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic

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.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypertension; Lactones; Obesity; Orlistat; Risk Factors; Treatment Outcome

Obesity is a growing public health problem worldwide. It is a particularly common problem among individuals with type 2 diabetes mellitus. The magnitude of obesity, the central location of fat, and a history of weight gain are independent risks for developing diabetes mellitus. Potential factors implicated in the pathogenesis of diabetes mellitus in obese patients include increased plasma free fatty acid concentrations, increased production of cytokines, increased leptin levels, and increased levels of a recently discovered protein called resistin. Epidemiological and interventional studies suggest that even modest loss of body weight, either by changes in lifestyle or pharmacological means is associated with significant amelioration of insulin resistance and improvement in diabetes mellitus control. Treatment of obesity is an important therapeutic goal in the management of patients with type 2 diabetes mellitus.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat; Prevalence; Weight Loss

Topics: Adipose Tissue; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Endocrinology; Humans; Lactones; Models, Biological; Molecular Biology; Neuropeptides; Obesity; Orlistat

Topics: Anti-Obesity Agents; Cyclobutanes; Energy Metabolism; Humans; Lactones; Neuropeptides; Obesity; Orlistat

In excess of 55% of adults in the United States are classified as either overweight (body mass index = 25-29.9 kg.m(-2)) or obese (body mass index > or = 30 kg.m(-2)). To address this significant public health problem, the American College of Sports Medicine recommends that the combination of reductions in energy intake and increases in energy expenditure, through structured exercise and other forms of physical activity, be a component of weight loss intervention programs. An energy deficit of 500-1000 kcal.d-1 achieved through reductions in total energy intake is recommended. Moreover, it appears that reducing dietary fat intake to <30% of total energy intake may facilitate weight loss by reducing total energy intake. Although there may be advantages to modifying protein and carbohydrate intake, the optimal doses of these macronutritents for weight loss have not been determined. Significant health benefits can be recognized with participation in a minimum of 150 min (2.5 h) of moderate intensity exercise per week, and overweight and obese adults should progressively increase to this initial exercise goal. However, there may be advantages to progressively increasing exercise to 200-300 min (3.3-5 h) of exercise per week, as recent scientific evidence indicates that this level of exercise facilitates the long-term maintenance of weight loss. The addition of resistance exercise to a weight loss intervention will increase strength and function but may not attenuate the loss of fat-free mass typically observed with reductions in total energy intake and loss of body weight. When medically indicated, pharmacotherapy may be used for weight loss, but pharmacotherapy appears to be most effective when used in combination with modifications of both eating and exercise behaviors. The American College of Sports Medicine recommends that the strategies outlined in this position paper be incorporated into interventions targeting weight loss and the prevention of weight regain for adults.

Topics: Adult; Body Mass Index; Cyclobutanes; Diet Therapy; Dietary Fats; Energy Intake; Exercise Therapy; Health Behavior; Humans; Lactones; Life Style; Obesity; Orlistat; Physical Endurance; Secondary Prevention; Weight Gain; Weight Lifting; Weight Loss

Obesity, despite becoming a recognized epidemic in the United States and many countries around the world cannot be necessarily defined, measured, and treated in a simplified fashion. Numerous organizations have classified overweight and obesity using different anthropometric parameters. Older methods to determine the extent of obesity, such as crude weight and skin calipers, contain serious limitations. For example, measuring abdominal obesity cannot be determined using calipers. Other methods such as lean body mass, body mass index (BMI), and waist-to-hip ratio (WHR) are more commonly used in epidemiologic studies but also contain inherent errors. More expensive and technologically advanced methods, such as densitometry, dual-energy x-ray absorptiometry (DEXA), and bioelectrical impedance analysis are also helpful, but the time and cost of using these methods in large-scale studies are a concern. Numerous options for treating obesity exist, and the clinician should be made aware of their strengths and limitations. Lifestyle changes are not only cost effective, but may be the best approach for individuals who desire to lose weight or to maintain their weight while becoming more fit. The addition of drug therapy is also a possibility. A variety of pharmacotherapy interventions are available to the patient on a short-term basis. In addition, two drugs have Food and Drug Administration approval for the long-term treatment of obesity. Drug therapy should be viewed as adjunctive treatment to lifestyle changes for the individuals who qualify based on their BMI and other comorbidities. Drug therapy carries several adverse effects, and the potential for indefinite treatment continues to be an area of controversy. Therefore, a multidisciplinary approach to treating obesity must be considered in any patient who is obese. These treatments in combination with drug therapy in some cases have provided some of the best results in randomized trials. Obesity needs to be considered a chronic disease that requires long-term commitment and multidisciplinary treatment to achieve the desired results. Unless therapy is individualized, it may be difficult to reverse the dramatic trends in obesity rates that have been observed over the past several decades.

Topics: Absorptiometry, Photon; Anti-Obesity Agents; Body Composition; Body Constitution; Body Mass Index; Cyclobutanes; Diet, Reducing; Exercise; Humans; Lactones; Life Style; Obesity; Orlistat; Prevalence

The pathogenesis of obesity is complex and miscellaneous endogenous as well exogenous factors modulate body weight. The therapeutic strategies are equally complex and may include the option of antiobesity drugs. Despite the availability of drugs they are only seen as adjuvant therapeutic options and the corner stone of obesity therapy remain permanent life style changes. Presently only orlistat and sibutramin are approved for the pharmacological therapy of obesity in Switzerland. The indications and contraindications of these new antiobesity drugs are discussed. In addition a new concept of a stepped care approach in weight management is presented.

Topics: Appetite Depressants; Combined Modality Therapy; Contraindications; Cyclobutanes; Family Practice; Humans; Lactones; Life Style; Obesity; Orlistat; Switzerland

Patients often seek help from their primary care physician for weight loss, so familiarity with pharmacologic options and their risks is important. Anorexiants have been available for decades and are relatively safe. Orlistat and sibutramine are two of the newer medications that patients may have heard about in television, newspaper, and magazine advertising. In addition, patients often ask for advice regarding various herbal or nonprescription medications for weight loss. In this article, the authors help physicians prepare to address these questions.

Topics: Anti-Obesity Agents; Appetite Depressants; Chronic Disease; Contraindications; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

Obesity is one of the most common medical problems in the United States and a risk factor for illnesses such as hypertension, diabetes, degenerative arthritis and myocardial infarction. It is a cause of significant morbidity and mortality and generates great social and financial costs. Obesity is defined as a body mass index greater than 30. Many patients accomplish weight loss with diet, exercise and lifestyle modification. Others require more aggressive therapy. Weight loss medications may be appropriate for use in selected patients who meet the definition of obesity or who are overweight with comorbid conditions. Medications are formulated to reduce energy intake, increase energy output or decrease the absorption of nutrients. Drugs cannot replace diet, exercise and lifestyle modification, which remain the cornerstones of obesity treatment. Two new agents, sibutramine and orlistat, exhibit novel mechanisms of action and avoid some of the side effects that occurred with earlier drugs. Sibutramine acts to block uptake of serotonin, norepinephrine and dopamine, while orlistat decreases fat absorption in the intestines.

Topics: Algorithms; Anti-Obesity Agents; Appetite Depressants; Basal Metabolism; Body Mass Index; Cyclobutanes; Decision Trees; Diagnosis, Differential; Energy Intake; Exercise; Feeding Behavior; Humans; Lactones; Life Style; Lipase; Obesity; Orlistat; Risk Factors

Many experts consider obesity a chronic disease that may require long-term therapy. A loss of 5-15% of body weight is associated with improvements in cardiovascular risk factors and morbidity. However, most studies show that the majority of patients who lose weight relapse. Patients may be unable to maintain a low energy intake when confronted with an almost limitless supply of food. Moreover, a number of physiological mechanisms favour a set point for body weight, that may be altered with anti-obesity drugs.. In the current paper we describe actions and effects of current anti-obesity drugs. The centrally acting drug, sibutramine, is an adrenaline and serotonine re-uptake inhibitor which was recently approved in the USA for obesity. The USA, the European Union and Norway have approved orlistat, a pancreatic lipase inhibitor for weight reduction for up to two years. Patients must maintain a low fat intake in order to avoid gastrointestinal discomfort. In recent studies, orlistat and diet reduced body weight by 9% versus 6% on placebo and diet. No studies have documented long-term safety of anti-obesity drugs.. Treatment of a lifestyle-related disease like obesity with medications is controversial, however, such treatment may not differ substantially from treatment of type II diabetes, hyperlipidaemia or hypertension.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Fenfluramine; Humans; Lactones; Leptin; Obesity; Obesity, Morbid; Orlistat; Phentermine; Selective Serotonin Reuptake Inhibitors; Weight Loss

Obesity is a major global public health problem. In many instances, a combination of diet modification, increased physical activity and behavior therapy fail or are insufficient for sustained weight loss. In these situations, drug therapy may be helpful. However, drug treatment of obesity resulted in unexpected devastating events in recent years. In the late sixties, aminorex caused an epidemic of pulmonary hypertension with high mortality rates. Dexfenfluramine and phentermine were also associated with the development of pulmonary hypertension and with alarming reports of cardiac valvular abnormalities. Therefore, these drugs were withdrawn from the market. Newer drugs, like sibutramine, a serotonin and norepinephrine reuptake inhibitor, and orlistat, a specific lipase inhibitor, reduce body weight significantly compared to placebo. In combination with a hypocaloric diet, weight loss of three to ten kilos can be achieved. Pharmacotherapy is limited to patients with a body mass index greater than 30 kg/m2, if non-pharmacological treatment programs have failed. The drugs should be prescribed under strict medical surveillance only.

Topics: Aminorex; Anti-Obesity Agents; Appetite Depressants; Chronic Disease; Combined Modality Therapy; Cyclobutanes; Dexfenfluramine; Diet, Reducing; Drug and Narcotic Control; Germany; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Lactones; Obesity; Orlistat; Phentermine

Obesity is epidemic and dangerous. Weight loss is difficult but worth the effort. Although new weight-loss drugs are available, there are no magic bullets: to lose weight and keep it off, people must eat less and exercise more. This article presents a practical approach on how physicians can help their patients lose weight through diet, behavior modification, and adjunctive pharmacologic therapy. An appropriate initial goal is to lose 5% to 10% of one's baseline weight over 3 to 6 months. Drug therapy should not be used in isolation, but it can be an adjunct to diet, exercise, and behavior modification if a patient is committed and able to make necessary changes in eating and activity, and if the patient has a BMI of 30 or higher or a BMI greater than 27 with weight-related comorbid conditions. Anorectic therapy is unlikely to succeed and should be stopped if the patient does not lose at least 4 lb in the first 4 weeks of therapy. Orlistat is unlikely to be of benefit if patients do not lose at least 3% of their baseline weight by 12 weeks. Because obesity is a chronic disease, drug treatment should be continued indefinitely. The physician and patient must understand the intention to treat long-term. The weight loss plan devised should improve upon previous plans: for example, implementing a regular, convenient exercise program that had not been included in the past, or offering pharmacotherapy.

Topics: Anti-Obesity Agents; Antidepressive Agents; Appetite Depressants; Behavior Therapy; Chronic Disease; Cyclobutanes; Diet, Reducing; Exercise; Gastric Bypass; Humans; Lactones; Obesity; Orlistat; Prevalence; Randomized Controlled Trials as Topic; United States

Topics: Adolescent; Adult; Age Factors; Aged; Anti-Obesity Agents; Appetite Depressants; Biliopancreatic Diversion; Body Weight; Child; Cross-Sectional Studies; Cyclobutanes; Diet; Exercise; Female; Gastric Bypass; Gastroplasty; Health Education; Humans; Lactones; Life Style; Male; Middle Aged; Nutritional Physiological Phenomena; Obesity; Obesity, Morbid; Orlistat; Primary Prevention; Psychotherapy; Risk Factors; Sex Factors; Spain

Obesity is a major risk factor for the development of type 2 diabetes and is an important obstacle to the management of this disease. The increasing incidence of both obesity and type 2 diabetes makes management of these related conditions particularly important. Conventional approaches to the management of type 2 diabetes that focus primarily on improving glycaemic control-notably insulin or sulphonylurea treatment-often lead to weight gain, which is particularly detrimental to patients with type 2 diabetes. By contrast, reducing body weight in such patients improves glycaemic control and other cardiovascular risk factors associated with the metabolic syndrome. This suggests that weight reduction is a rational option in the management of obese patients with type 2 diabetes. While reductions in body weight of approximately 10% have been achieved in some studies, this is difficult to achieve in real life, especially for patients with type 2 diabetes. Weight management agents such as sibutramine and orlistat, used as part of an integrated programme of diet, physical activity and behavioural therapy, are thus an attractive early option for the management of type 2 diabetes in obese patients.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat; Weight Loss

The aim of this short review is to summarize our knowledge on the pharmacological treatment of obesity. We consider first the old molecules, mostly amphetamine derivatives, which tend to be abandoned and second, the more recent ones which just appeared or are just about to become available. We also envision some therapeutical perspectives derived from recent advances in molecular biology. Although, it is "scientifically correct" to deliver an optimistic message regarding the possibility of finding an effective and safe treatment of obesity in the near future, we think that this is, on the contrary, an unrealistic goal.

Topics: Amphetamines; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Enzyme Inhibitors; Humans; Lactones; Lipase; Molecular Biology; Obesity; Orlistat; Safety; Selective Serotonin Reuptake Inhibitors

Obesity increases the risk of several serious health problems, including heart disease, type II diabetes mellitus, hypertension, and osteoarthritis. Patients taking certain psychotropic medications may gain a significant amount of weight (as much as a 5% increase in body weight within 1 to 2 months), placing them at risk for obesity. Body weight monitoring and prudent drug selection are the best approaches to preventing weight gain in patients taking psychotropic drugs. When weight gain (> 5% of initial body weight) is unavoidable, intervention counseling should begin. Nonpharmacologic measures for managing weight gain include a balanced deficit diet of 1000 calories and higher, depending on the patient's weight; 30 to 60 minutes of physical activity daily; and behavioral training to restrain excess caloric intake. Each of these measures requires a considerable commitment on the part of the patient and works best with support from the physician and weight-loss support groups. Drug therapy for weight loss is available (at present, sibutramine is the only approved appetite suppressant in the United States); however, for most patients already being treated with a psychotropic agent, the risks (such as drug interactions, adverse events, compliance problems) of adding an antiobesity agent probably outweigh the benefits. Surgical intervention for obesity should be reserved for morbidly obese patients whose disease is intractable to medical therapy.

Topics: Anti-Obesity Agents; Appetite Depressants; Behavior Therapy; Cyclobutanes; Diet, Reducing; Energy Intake; Exercise; Humans; Lactones; Obesity; Obesity, Morbid; Orlistat; Psychotropic Drugs; Self-Help Groups; Weight Gain

The prevalence of overweight and obesity has increased dramatically in the recent decades, and obesity is now a major public health problem. Obesity negatively influences an individual's health by increasing mortality and raising the risk for multiple medical conditions such as type 2 diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. In addition, the obese individual is often the brunt of social discrimination. Weight loss has been shown to reduce the risk for many of these comorbid conditions. A multifaceted approach to the obese patient should include identifying potential causes for weight gain, outlining medical conditions that would benefit by weight loss, and tailoring a weight loss program that is safe and effective for the individual. Components of a successful weight loss program include dietary intervention, recommendations for physical activity, behavior modification, and, in a select group of patients, pharmacologic or surgical intervention.

Topics: Anti-Obesity Agents; Appetite Depressants; Cognitive Behavioral Therapy; Cyclobutanes; Exercise; Gastric Bypass; Humans; Lactones; Lipase; Obesity; Obesity, Morbid; Orlistat; Selective Serotonin Reuptake Inhibitors; Weight Loss

The statistics are staggering: 59.4% of men, 50.7% of women, and 54.9% of the total population are overweight. Consequently, heightened efforts are being directed to control this epidemic. Clinicians have shown a renewed interest in the use of appetite suppressants and other antiobesity agents concomitantly with conventional treatment of diet education, exercise training, and lifestyle modification. This article reviews appetite suppressants both from a historical perspective and currently, and then presents a rationale for the continued use of antiobesity agents in the management of obesity.

Topics: Anti-Obesity Agents; Body Mass Index; Cyclobutanes; Female; Follow-Up Studies; Humans; Lactones; Male; Obesity; Orlistat; Phentermine; Weight Loss

Obesity is increasing at an alarming rate. During the past decade, the overall prevalence of obesity in the United States increased over 30%, with more than one third of the adult population meeting the definition of being overweight.. We review current and emerging therapies, present outcome data from a large clinical practice, and discuss challenges for physicians and researchers involved in obesity treatment.. Because obesity is a risk factor for numerous medical disorders and excess mortality, it is imperative that effective treatments be developed. While the current conservative therapies produce short-term weight losses, they are ineffective in the long term. Some obesity treatments are controversial, most notably the increasing use of anorexiant medications. For example, the Food and Drug Administration (FDA) recently requested the withdrawal of two widely used medications because of concerns about side effects. Currently, therapies that combine psychosocial interventions, drugs, and extended maintenance appear to have the most promising long-term benefits.. Long-term treatment, including extended pharmacotherapy, may be necessary for many obese patients. Broader definitions of treatment outcome and success, including improvements in comorbid conditions, physical activity, and quality of life are needed.

Topics: 1-Naphthylamine; Adrenergic beta-Agonists; Appetite Depressants; Behavior Therapy; Caffeine; Cyclobutanes; Diethylpropion; Ephedrine; Fenfluramine; Fluoxetine; Humans; Lactones; Leptin; Lipase; Obesity; Orlistat; Phentermine; Proteins; Sertraline

Reduction in overweight and obesity management have been shown to be important in the treatment of diabetes. Even modest weight loss produces important metabolic benefits if maintained over the long term. Thus a pharmacotherapeutic agent that could produce a maintained weight loss, and had a good safety profile, would revolutionize the treatment of type II (non-insulin-dependent) diabetes. Two obesity management agents, orlistat and sibutramine, are expected shortly for the long-term treatment of obesity. These agents have been shown to be effective in 1-2-year-long studies in obese, non-diabetic patients. They produced significant improvements in weight loss compared with placebos. The efficacy of these obesity management agents has also been demonstrated in short-term studies in patients with type II diabetes. As yet, however, few studies have investigated the long-term effects of these treatments in diabetic patients. Obese patients with type II diabetes receiving 12 months of dexfenfluramine therapy showed greater reductions in weight, fasting blood glucose and HbA1c levels than the controls. A 1-year study of orlistat treatment for patients with type II diabetes revealed substantial benefits in glycaemic control, even though weight loss was only moderate. A 1-year treatment with orlistat also substantially prevented the conversion of impaired glucose tolerance into type II diabetes (conversion rate 2.6% in the orlistat group versus 10.4% in the placebo group). Encouraging results have also been reported from studies on orlistat and sibutramine in non-diabetics, with beneficial effects seen for weight loss and other diabetes risk factors. Antiobesity pharmacotherapy therefore appears to offer a realistic option for the prevention of diabetes, although further studies are required to determine its efficacy.

Topics: Appetite Depressants; Blood Glucose; Controlled Clinical Trials as Topic; Cyclobutanes; Dexfenfluramine; Diabetes Mellitus, Type 2; Humans; Lactones; Longitudinal Studies; Obesity; Orlistat; Weight Loss

The medical model of obesity treatment--combining diet, exercise, and behavior modification with antiobesity agents--suffered a setback when fenfluramine and dexfenfluramine were withdrawn from the market because of an association between these medications and valvular regurgitation. The Food and Drug Administration has recently approved sibutramine (Meridia), a norepinephrine and serotonin reuptake inhibitor that was originally developed as an antidepressant, but which has also been shown to reduce weight. In a 1-year placebo-controlled trial, 65% of patients receiving 15 mg sibutramine daily lost more than 5% of their body weight, compared with 29% of patients receiving a placebo; 39% of patients in the sibutramine group lost more than 10% of their body weight, compared with 8% of patients in the placebo group. Health benefits observed in patients receiving sibutramine include reductions in levels of triglycerides, uric acid, total cholesterol, and low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol levels. Another antiobesity drug currently under review by the Food and Drug Administration is orlistat (Xenical), a pancreatic lipase inhibitor that reduces the absorption of dietary fat by approximately 30%, thus reducing energy intake. In a 1-year placebo-controlled trial, 55% of patients receiving orlistat lost more than 5% of their body weight, and 25% lost more than 10% of their body weight, compared with 33% and 15%, respectively, of patients in the placebo group. In addition, orlistat slowed the rate of weight regain in the second year of treatment. Health benefits demonstrated in clinical trials of orlistat include reduced LDL cholesterol levels and increased levels of HDL cholesterol, reduced blood pressure and fasting insulin levels, improved oral glucose tolerance test outcomes, and improved glycemic control in obese patients with diabetes. The future of the pharmacologic treatment of obesity is promising. Many new antiobesity agents are in the early stages of development, and our understanding of the body's weight-regulating mechanisms is advancing steadily. Human trials of recombinant leptin are underway. Other promising compounds include those that block the Neuropeptide Y5 and Y1 (NY5, NY1) and Melanocortin-4 (MC4) receptors, stimulate uncoupling proteins, and unbind corticotrophin-releasing factor from its binding protein. As better medical treatments for obesity become available, the focus

Topics: Appetite Depressants; Chronic Disease; Cyclobutanes; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat

Drugs are part of the multimodal approach of modern obesity treatment. In the near future Sibutramine, a centrally acting serotoninergic and noradrenergic agonist and Orlistat, a peripherally acting lipase inhibitor will be available for treatment of obesity. Since all drugs employed should be applicable for years the latter substance might be especially useful for the mandatory longterm treatment of obese patients.

Topics: Appetite Depressants; Cyclobutanes; Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Treatment Outcome

Topics: Anti-Obesity Agents; Cyclobutanes; Diet, Fat-Restricted; Family Practice; Humans; Intestinal Absorption; Lactones; Obesity; Orlistat; Weight Gain

Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker.. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment.. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention.. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Topics: Adiponectin; Adolescent; Adult; Aged; Asian People; Blood Glucose; Body Fat Distribution; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cyclobutanes; Fasting; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Lactones; Malaysia; Middle Aged; Obesity; Orlistat; Risk; Treatment Outcome; Waist Circumference; Young Adult

Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR).. 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations.. 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group.. 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.

Topics: Adolescent; Adult; Aged; Anthropometry; Anti-Obesity Agents; Blood Pressure; Cholesterol; Cyclobutanes; Endothelium, Vascular; Female; Heart Rate; Humans; Lactones; Laser-Doppler Flowmetry; Male; Microvessels; Middle Aged; Obesity; Orlistat; Prospective Studies; Young Adult

Various cytochrome P450 isoforms modulate sibutramine activity and influence sibutramine plasma levels and pharmacokinetics. However, there are no available data to demonstrate the association of these polymorphisms with the clinical outcomes of sibutramine administration.. This study was a sub-investigation of a 12-week, double-blind, placebo-controlled trial examining the additive effect of orlistat on sibutramine. The final analysis was restricted to 101 women who had fulfilled the protocol. We evaluated the effects of genetic polymorphisms of CYP3A5, CYP2C19 and CYP2B6 on the % weight loss and the occurrence of adverse events.. The change of pulse rate from baseline value was affected by both CYP2B6 and CYP3A5 genetic polymorphisms (P<.01 for CYP3A5 and P=.01 for CYP2B6). Both CYP2B6 and CYP3A5 showed gene-gene interactions (P<.01). After adjusting for significant variables in the backward stepwise regression model, the change of pulse rate and time-dependent weight reduction were significant only among the CYP2B6 genotypes (P=.027 and P<.01, respectively).. The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment.

Topics: Adolescent; Adult; Alleles; Cyclobutanes; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Double-Blind Method; Female; Genotype; Heart Rate; Humans; Lactones; Middle Aged; Orlistat; Polymorphism, Genetic; Prospective Studies; Pulse; Regression Analysis; Treatment Outcome; Weight Loss; Young Adult

Little data exists concerning whether eating behaviors determine the response to orlistat treatment, especially with added anorectic agents. This study was a sub-investigation of a 12-week randomized controlled trial for the additive effect of orlistat on sibutramine treatment. The analysis presented here was restricted to 98 women who had fulfilled the protocol. The Dutch eating behavior questionnaire and three-factor eating questionnaire were used to assess eating behaviors. Scores of emotional eating, external eating, disinhibition and hunger are significantly interrelated. Using multiple logistic analysis with adjustment for potential confounders, such as age, initial BMI and the other 2 eating behavior scores, traits of emotional eating (OR 0.30, 95% CI 0.13-0.74) and disinhibition (OR 0.61, 95% CI 0.40-0.82) have a significant influence on prediction for additional 5% weight loss in the treatment with orlistat and sibutramine. Subjects with less vulnerability to emotional cues had significantly more weight loss with orlistat treatment and anorectic agents.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Double-Blind Method; Drug Therapy, Combination; Emotions; Feeding Behavior; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Prospective Studies; Surveys and Questionnaires; Time Factors; Treatment Outcome; Weight Loss

No clinical studies on the lipolytic effect of guanine nucleotide-binding protein β3 subunit gene (GNB3) 825T polymorphism have been performed. This study was a subinvestigation of a 12-week randomized controlled trial (NCT01184560) for the additive effect of orlistat on sibutramine treatment. The analysis involved 101 obese females aged 18-49 years, genotyped at the GNB3 825 locus. To exclude any influence from potential confounders, we used an analysis of covariance model. After the intervention, fat mass proportion in total weight loss was significantly lower in subjects with a T allele than in those without a T allele (p = 0.034). GNB3 825T allele was associated with blunted fat mass reduction in obese females.

Topics: Adiposity; Adult; Alleles; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Drug Synergism; Female; Genotype; GTP-Binding Proteins; Heterotrimeric GTP-Binding Proteins; Humans; Lactones; Middle Aged; Obesity; Orlistat; Polymorphism, Genetic; Weight Loss

Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI <25 kg/m(2)) were treated with metformin for 6 months. Twenty-five normal weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p < 0.001). In overweight/obese patients with PCOS, weight loss resulted in a fall in lipocalin-2 levels (p < 0.001). In normal weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

Topics: Acute-Phase Proteins; Adolescent; Adult; Anti-Obesity Agents; Caloric Restriction; Combined Modality Therapy; Cyclobutanes; Down-Regulation; Exercise Therapy; Female; Humans; Lactones; Lipocalin-2; Lipocalins; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Proto-Oncogene Proteins; Weight Loss; Young Adult

Intentional weight loss results in improvement in mood. Very few data exist regarding the effects of sibutramine on the mood of obese and overweight patients in general clinical samples. Moreover, no study has evaluated the effects of orlistat treatment on mood. The purpose of our study was to assess the effects of sibutramine and orlistat on mood in obese and overweight subjects.. Sixty obese and overweight women were divided into three groups. The first group (n=20) received a low-calorie diet and sibutramine 10mg; the second group (n=20) received a low-calorie diet and orlistat 120 mg three times a day, and the third group received only the low-calorie diet.. A psychiatric assessment was performed with the Hamilton Depression Rating Scale (HAMD) before and after 3 months of treatment. In all the groups a statistically significant decrease in HAMD scores was observed. However, the decrease in the sibutramine group was greater compared to that observed in the two other groups (P<0.01). These results suggest that sibutramine treatment may improve mood more than diet alone or orlistat therapy in a general clinical sample of obese patients.

Topics: Adult; Affect; Analysis of Variance; Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Cyclobutanes; Diet, Reducing; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Overweight; Prospective Studies; Psychometrics; Treatment Outcome; Weight Loss

Central counter-regulatory mechanisms, including those related to the orexigenic hormone neuropeptide Y (NPY), may limit the weight loss observed with conventional pharmacological monotherapy. This study evaluated whether blockade of the NPY Y5 receptor (NPY5R) with the selective antagonist MK-0557 potentiates sibutramine and orlistat weight loss effects.. Obese patients (497, BMI 30 to 43 kg/m2) were randomized to 1 of 5 treatment arms [placebo, n = 101; sibutramine 10 mg/d, n = 100; MK-0557 1 mg/d plus sibutramine 10 mg/d, n = 98; orlistat 120 mg TID, n = 99; MK-0557 1 mg/d plus orlistat 120 mg TID, n = 99] in conjunction with a hypocaloric diet for 24 weeks. The all-patients-treated population, imputing missing data using last observation carried forward, was used to assess weight loss from baseline.. The study was completed by 71% of patients in placebo, 76% in sibutramine alone, 79% in MK-0557 + sibutramine, 69% in orlistat alone, and 76% in MK-0557 + orlistat groups. Least squares (LS) mean difference [95% confidence interval (CI)] in weight change from baseline between MK-0557 + sibutramine and sibutramine alone was -0.1 (-1.6, 1.4) kg (p = 0.892) and between MK-0557 + orlistat and orlistat alone was -0.9 (-2.4, 0.6) kg (p = 0.250). Sibutramine alone induced a LS mean weight loss of -5.9 (-6.9, -4.9) kg vs. -4.6 (-5.7, -3.6) kg for orlistat (p = 0.097). There were no serious drug-related adverse events and MK-0557 was well tolerated.. Blockade of the NPY5R with the potent antagonist MK-0557 did not significantly increase the weight loss efficacy of either orlistat or sibutramine monotherapy.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Cyclobutanes; Cyclohexanes; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Pyrazoles; Receptors, Neuropeptide Y; Spiro Compounds; Weight Loss

To describe the comparative efficacy of orlistat and sibutramine in an obesity management program, with specific attention to compliance and weight regains after noncompliance. We prospectively evaluated 182 obese patients who were randomized to treatment with orlistat (n=98) or sibutramine (n=84) along with the diet and exercise prescriptions. Compliance (or compliant patient) was defined as adherence to scheduled visit times (at 3- month intervals) and following the prescribed drug regimen. A telephone survey was conducted in case of noncompliance. Significant body weights improvements were seen in both treatment groups. Patients lost a mean of 7.6+/-2.8% and 10.5+/-2.9% of initial body weights after a mean drug use of 8.8+/-5.7 and 8.3+/-3.7 months in the orlistat and sibutramine groups, respectively (p<0.05 vs. initial body weight). Patients in the sibutramine group lost more weight than the orlistat group (p<0.05). A total of 102 patients (56%) were compliant (53.1% in the orlistat group and 59.5% in the sibutramine group). Factors associated with compliance included weight reduction of more than 5% in the first 3 months and adherence to physical activity. Higher initial body weight, prior anti-obesity therapy, number of concurrent medications, and comorbidity were associated with noncompliance. Weight regains in noncompliant patient were a mean of 5.2+/-5.1 kg after a mean period of 9.2+/-4.2 months in the orlistat group, and a mean of 6.1+/-3.8 kg after a mean period of 9.1+/-3.9 months in the sibutramine group (p<0.05 vs. last visit for both groups, p>0.05 between groups). Both drugs in an obesity management program can achieve substantial weight loss. However, noncompliance and rebound weight regain after noncompliance are considerable problems.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Exercise Therapy; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Patient Compliance; Prospective Studies; Weight Gain; Weight Loss

The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients, with a specific attention to cardiovascular effects and to side effects because of this treatment.. Patients were enrolled, evaluated and followed at three Italian Centres of Internal Medicine. We evaluated 115 obese and hypertensive patients. (55 males and 60 females; 26 males and 29 females, aged 50 +/- 4 with orlistat; 28 males and 30 females, aged 51 +/- 5 with sibutramine). All patients took antihypertensive therapy for at least 6 months before the study. We administered orlistat or sibutramine in a randomized, controlled, double-blind clinical study. We evaluated anthropometric variables, blood pressure and heart rate (HR) during 12 months of this treatment.. A total of 113 completed the 4 weeks with controlled energy diet and were randomized to double-blind treatment with orlistat (n = 55) or sibutramine (n = 58). Significant body mass index (BMI) improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups, and body weight (BW) improvement was obtained after 9 (p < 0.05) and 12 (p < 0.02) months in both groups. Significant waist circumference (WC), hip circumference (HC) and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p < 0.05, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05) was present in orlistat group after 12 months. Lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides] reduction (p < 0.05, respectively) was observed in orlistat group and triglyceride reduction (p < 0.05) in sibutramine group after 12 months. No significant change was observed in sibutramine group during the study. No significant HR variation was obtained during the study in both groups. Of the 109 patients who completed the study, 48.1% of patients in the orlistat group and 17.5% of patients in the sibutramine group had side effects (p < 0.05 vs. orlistat group). Side-effect profiles were different in the two treatment groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pressure (both SBP and DBP) in two patients, but it has been controlled by antihypertensive treatment. The vitamin changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation.. Both orlistat and sibutramine are effective on anthropometric variables during the 12-month treatment; in our sample, orlistat has been associated to a mild reduction in blood pressure, while sibutramine assumption has not be associated to any cardiovascular effect and was generically better tolerated than orlistat.

Topics: Analysis of Variance; Appetite Depressants; Blood Pressure; Cyclobutanes; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Lactones; Male; Middle Aged; Obesity; Orlistat

The aim of this study was to evaluate decrease in waist circumference in obese patients receiving different anti-obesity treatments. The study was designed as a short-term (12 weeks), open-label, and randomized trial. Eighty six patients (70 females, 81.4%; mean age 41.09+/-8.73 years, mean BMI 36.1+/-4.3 kg/m2) were randomized to four different therapy groups. The primary outcome parameters were waist circumference and body mass index (BMI). The therapy groups were a) diet+sibutramine 1 x 10 mg/d (n=22), b) diet+orlistat 3 x 120 mg/d (n=25), c) combination of diet+sibutramine+orlistat (n=20) and d) diet (n=19). Combination therapy was more effective than diet and orlistat mono-therapy (p<0.0001 for all), but not significantly superior to sibutramine mono-therapy (p=0.072) in decreasing BMI. Sibutramine mono-therapy was significantly more effective in inducing BMI decrease compared with orlistat mono-therapy (p=0.039). The association between change in BMI and change in waist circumference was strongest in the orlistat mono-therapy group (P interaction=0.003). This means that patients taking orlistat experienced more decrease in waist circumference (3.4 cm, R2=0.29) per unit decrease in BMI compared to patients under combination therapy (2.6 cm, R2=0.25, P interaction = 0.015) and patients taking sibutramine (1.8 cm, R2=0.19, P interaction=0.026). In the diet therapy group decline in waist circumference was independent of BMI (1.9 cm, R2=0.02, P interaction=0.076). Although combination therapy and sibutramine mono-therapy were more effective in decreasing BMI, reduction in waist circumference and BMI was most significantly associated with the orlistat mono-therapy group. This may hint at the possibility of orlistat inducing weight loss mainly in the abdominal area targeted to reduce cardiovascular risk.

Topics: Adult; Anthropometry; Anti-Obesity Agents; Body Mass Index; Body Weight; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Drug Therapy, Combination; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Statistics as Topic

Sibutramine and orlistat are currently used for weight loss. We aimed to investigate the effect of orlistat and sibutramine combination therapy in treatment of obese women.. Study population consisted of 89 obese women who had a body mass index > or = 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51-3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29 patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects.. Mean weight loss was 5.5 +/- 4.9 kg (p = 0.024) in group 1, 10.1 +/- 3.6 kg (p < 0.001) in group 2, 10.8 +/- 6.6 kg (p < 0.001) in group 3 after the six months. Weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 +/- 3.1% in group 1, 10.2 +/- 4.8% in group 2, 10.6 +/- 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and percentage of weight loss were not different between group 2 and group 3.. These three regimens had different results on weight loss in obese women. Combination drug therapy and sibutramine therapy were both more effective than orlistat therapy alone. However, no significant difference was noted between combination drug therapy and sibutramine treatment groups.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diet, Reducing; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese diabetic patients of both sexes, with specific attention to metabolic pattern-induced changes and cardiovascular effects.. Patients were enrolled, evaluated, and followed in 3 Italian Centres of Internal Medicine. We evaluated 144 obese diabetic patients. All were required to have been diagnosed as being diabetic for at least 6 months, and had glycaemic control with diet alone or diet and oral hypoglycaemic agents. We administered orlistat (360 mg/d) or sibutramine (10 mg/d) in a randomized, controlled, double-blind clinical study, and evaluated anthropometric variables, glycaemic control, blood pressure and heart rate (HR) during 12 months of this treatment.. A total of 141 (69 males and 72 females; 35 males and 36 females, aged 53 +/- 5 yr with orlistat; 34 males and 36 females, aged 51 +/- 4 yr with sibutramine) completed the 4 weeks on controlled-energy diet and were randomized to double-blind treatment with orlistat (n=71) or sibutramine (n=70). Significant body mass index (BMI) improvement was present after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in both groups. Significant waist circumference (WC), hip circumference (HC), and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p<0.05, respectively) in both groups. Significant HbA1c decrease was obtained after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) levels were significantly decreased in both groups (p<0.05 andp<0.02, respectively). Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p<0.05) was present in the orlistat group after 12 months. No significant change in blood pressure measurements was observed in the sibutramine group during the study. No significant HR variation was obtained during the study in either group. Of the 133 patients who completed the study, 33.8% of patients in the orlistat group and 13.2% of patients in the sibutramine group had side effects (p<0.05 vs orlistat group). Side effect profiles were different in the two treatmen groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pres sure (both SBP and DBP) in one patient, but it was controlled by anti-hypertensive treatment. The vita min changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation.. Both orlistat and sibutramine were effective on anthropometric variables and on metabolic pattern during the 12-month treatment; in our sample, orlistat appears to be slightly more efficacious as an anti-obesity drug, while sibutramine intake was not associated to any cardiovascular effect and was generally better tolerated than orlistat.

Topics: Anthropometry; Anti-Obesity Agents; Blood Pressure; Cyclobutanes; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Heart Rate; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Safety; Treatment Outcome; Weight Loss

To compare changes in anthropometric measures [body mass index (BMI), body weight] of obese patients treated with diet and exercise alone or additionally sibutramine, orlistat or the combination of both drugs, respectively. To describe encountered adverse effects.. Short-term (12 weeks), randomized, open-labeled trial. A total of 86 patients (18.6% male, age 41.1 +/- 8.7 years, BMI: 36.11 +/- 4.34 kg/m(2)) were randomized to (1) sibutramine group (10 mg/d, n = 22), or (2) orlistat group (3 x 120 mg/d, n = 25), or (3) combination group (10 mg sibutramine/d + 3 x 120 mg orlistat/d, n = 20), or (4) diet group (n = 19). The primary outcome parameter was a decrease in BMI. Additionally patient-reported adverse effects were reported.. The four interventional groups displayed decreases in BMI as follows: (1) -4.41 +/- 1.26 kg/m(2); (2) -3.64 +/- 0.97 kg/m(2); (3) -5.12 +/- 1.44 kg/m(2) and (4) -2.52 +/- 1.36 kg/m(2); with the diet group showing the significantly lowest decrease in BMI compared to the orlistat (P = 0.004), sibutramine (P < 0.001) or the combination groups (P < 0.001), respectively. Decreases in BMI did not statistically differed between the sibutramine group and the combination therapy group (P = 0.072). However, both treatment groups were significantly more efficient in decreasing BMI than the orlistat group (P < 0.001). In addition to well-known side effects, such as gastrointestinal disturbances, headache and dry mouth, newly described adverse effects were self-reported hypermenorrhea (13.6%, n = 3) with sibutramine and forgetfulness with orlistat (24%, n = 6).. In our study pharmacotherapy showed significant better results in the short-term management of obesity than dietary regimens alone. Sibutramine and sibutramine in combination with orlistat seemed to be equally effective in terms of weight reduction compared to orlistat monotherapy. Attention should be paid to the possibility of adverse effects.

Topics: Adult; Body Mass Index; Cyclobutanes; Diet, Reducing; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Prospective Studies; Time Factors; Weight Loss

Non-alcoholic steatohepatitis (NASH) is frequent in obese subjects and has a relatively benign course; however, it may progress to cirrhosis. Weight loss in these patients may alleviate the findings of NASH. The aim of this study was to investigate the effects of pharmacological anti-obesity therapies on the findings of NASH.. There were thirteen patients (9 women, 4 men) in sibutramine group and 12 patients (8 women, 4 men) in orlistat group. The mean ages and body-mass indexes of the two groups were 42.5 years, 37.3 kg/m2 and 43.2 years, 36.1 kg/m2, respectively.. The obese subjects with NASH were given sibutramine or orlistat for six months. Additionally, all patients were given a low caloric diet. Liver enzymes (AST, ALT, GGT and ALP), insulin resistance (analysed by HOMA) and hepatic ultrasound (US) findings were assessed at baseline and after 6 months.. Both sibutramine and orlistat significantly reduced body weight (10.2 and 8.4%, respectively), insulin resistance (47 and 40%, respectively), AST (41 and 39%, respectively), ALT (59 and 58%, respectively), and GGT serum levels (27 and 25%, respectively). The ultrasonographic regression in steatosis was observed in 11 patients who received sibutramine and 8 patients who received orlistat. During the treatment, unexpectedly significant increases in total alkaline phosphatase levels were found in both sibutramine and orlistat groups (9 and 14%, respectively).. The present study shows that both sibutramine-induced and orlistat-induced weight losses result in reduction of insulin resistance, and improvements in biochemical markers and US findings of NASH. Because the GGT levels decreased in both groups, the increased ALP levels might have another source.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Enzyme Inhibitors; Fatty Liver; Female; Humans; Insulin Resistance; Lactones; Lipase; Liver; Male; Obesity; Orlistat; Ultrasonography; Weight Loss

Some of our obese patients who were receiving 10 mg/day sibutramine reported feeling hunger at night. To address this, we designed a randomized, prospective clinical trial to study the efficacy and safety of 10 mg sibutramine twice daily (bid), and compare this treatment with 120 mg orlistat three times daily (tid) and 850 mg metformin (bid).. A total of 150 female patients with body mass index (b.m.i.) > 30 kg/m(2) were included. The subjects were all out-patients at the Başkent University Endocrinology and Metabolism Clinic. Each individual was assigned randomly to receive 10 mg sibutramine bid (group 1; n = 50; mean age 42.27 +/- 1.40 years), 120 mg orlistat tid (group 2; n = 50; mean age 42.13 +/- 1.32 years) or 850 mg metformin bid (group 3; n = 50; mean age 43.58 +/- 1.40 years). All patients took the medications for 6 months. Two patients from the sibutramine group and two from the orlistat group were withdrawn from the study because of side-effects.. After 6 months of treatment, the sibutramine, orlistat, and metformin groups all showed significantly reduced b.m.i. (13.57%, 9.06% and 9.90% respectively); waist circumference (10.43%, 6.64%, and 8.10% respectively); fasting and postprandial blood glucose levels; insulin resistance as assessed by the homeostasis model for assessment of insulin resistance (HOMA) (38.63%, 32.73% and 39.28%, respectively); levels of total cholesterol, low-density lipoprotein (LDLC) cholesterol, very low-density lipoprotein (VLDLC) cholesterol, triglyceride, lipoprotein (a), and apolipoprotein B; uric acid level; pulse rate; and systolic and diastolic blood pressure. None of the groups showed any significant changes in levels of high-density lipoprotein (HDLC) cholesterol, or apolipoprotein A1. There was a significantly greater fall in b.m.i. in the sibutramine group than in either of the other groups (p < 0.0001).. The results of this study confirm that sibutramine, orlistat and metformin are all effective and safe medications that reduce cardiovascular risk and can decrease the risk of type 2 diabetes mellitus in obese females. Overall, treatment with 10 mg sibutramine bid is more effective than orlistat or metformin therapy in terms of weight reduction.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Blood Glucose; Body Mass Index; Body Weight; Cyclobutanes; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Lactones; Metformin; Obesity; Orlistat; Postprandial Period; Safety; Treatment Outcome; Weight Loss

The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum leptin ratio during pharmacological therapy for obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus drug therapy. The patients were randomly assigned into three study groups: group I, fenproporex 25 mg/d (n = 10); group II, sibutramine 10 mg/d (n = 10); and group III, orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of leptin were examined at baseline and 2 months after therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial body weight, and the reduction was not different among the groups. Serum leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because leptin levels adjusted for body fat did not change after treatment. CSF leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After therapy, the CSF/serum leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P < 0.01), corresponding to a decrease of 33.3 +/- 22.5% for the CSF/serum leptin ratio. The percentage change in group III was significantly different from the positive variation on group I (11.9 +/- 42.1%; P = 0.006) and close to the statistical significance compared with the negative variation seen in group II (-7.6 +/- 27.8%; P = 0.06). Our results showed that the CSF/serum leptin ratio decreased after weight loss in obese women treated during 2 months with orlistat, whereas this ratio did not change in this period of time in obese women treated with fenproporex and sibutramine.

Topics: Adolescent; Adult; Amphetamines; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Leptin; Middle Aged; Obesity; Orlistat; Weight Loss

This study assessed whether adding orlistat to sibutramine would induce further weight loss in patients who previously had lost weight while taking sibutramine alone.. Patients were 34 women with a mean age of 44.1 +/- 10.4 years, weight of 89.4 +/- 13.8 kg, and body mass index (BMI) of 33.9 +/- 4.9 kg/m2 who had lost an average of 11.6 +/- 9.2% of initial weight during the prior 1 year of treatment by sibutramine combined with lifestyle modification. Patients were randomly assigned, in double-blind fashion, to sibutramine plus orlistat or sibutramine plus placebo. In addition to medication, participants were provided five brief lifestyle modification visits during the 16-week continuation trial.. Mean body weight did not change significantly in either treatment condition during the 16 weeks. The addition of orlistat to sibutramine did not induce further weight loss as compared with treatment by sibutramine alone (mean changes = +0.1 +/- 4.1 kg vs. +0.5 +/- 2.1 kg, respectively).. These results must be interpreted with caution because of the study's small sample size. The findings, however, suggest that the combination of sibutramine and orlistat is unlikely to have additive effects that will yield mean losses > or =15% of initial weight, as desired by many obese individuals.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Body Weight; Combined Modality Therapy; Cyclobutanes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lactones; Life Style; Middle Aged; Obesity; Orlistat; Pilot Projects; Time Factors

Bariatric surgery is the most efficient treatment for obesity. However, in some cases, weight regain can occur. Currently, it is unknown the best antiobesity medication (AOM) for such clinical situation. This study aims to evaluate the effect of AOM in patients with weight regain after bariatric surgery.. A retrospective cohort study from December 2010 to July 2019 with patients submitted to bariatric surgery that had weight regain and received AOM for at least 2 years.. Of 96 patients that had weight regain in the analyzed period and received AOM, 16 were excluded from the analysis due to non-compliance (n = 7), treatment failure (n = 5), intolerable side effects with all available AOM (n = 2), or interaction with other medications (n = 2). Eighty patients were included in the analysis. The mean age was 59.0 ± 10.1 years, 88.8% were female, 91.2% white, and most of them were submitted to gastric bypass (87.6%). The mean preoperative and nadir weight after surgery were 127.9 ± 25.5 kg and 84.7 ± 22.8 kg, respectively. At the initiation of AOM, the mean baseline weight was 99.4 ± 23.1 kg. After 2 years of follow-up, there was significant weight loss in the groups treated with topiramate-alone (- 3.2 kg), topiramate plus sibutramine (- 6.1kg), and orlistat-alone or in combination (- 3.9kg). No statistical difference was observed in the sibutramine-alone group.. Topiramate (alone or associated with sibutramine) and orlistat (alone or in combination) promoted significant weight loss after 2 years of use in patients submitted to bariatric surgery with weight regain.

Topics: Aged; Anti-Obesity Agents; Bariatric Surgery; Female; Humans; Male; Middle Aged; Obesity, Morbid; Orlistat; Retrospective Studies; Topiramate; Weight Gain; Weight Loss

Adiponectin and chemerin have been reported their associations with insulin resistance and chronic inflammation. However, the relationship between adiponectin and chemerin themselves has not been fully elucidated. Therefore, we investigated the effects of changes in adiponectin and chemerin levels after a weight intervention.. We recruited 136 healthy overweight or obese subjects from 2006 to 2009 and provided all participants lifestyle modification therapy with diet consultations over 16 weeks. We assigned the participants to take orlistat or sibutramine or to a no prescription group. We analyzed the data using paired t-tests, Pearson's partial correlation analysis, and stepwise multiple linear regression analysis.. ∆ in chemerin was positively correlated with ∆ in adiponectin (r = 0.29, p < 0.01), and these trends were similar in the insulin-resistant (r = 0.35, p = 0.03) and insulin-sensitive (r = 0.27, p < 0.01) groups. In multiple regression analyses, Δadiponectin, ΔQUICKI (quantitative insulin-sensitivity check index), Δglucose, and ΔDBP were significantly associated with Δchemerin in the insulin-resistant group, and initial chemerin level, ΔQUICKI, ΔBMI (body mass index), and taking orlistat were associated with Δchemerin in the insulin-sensitive group.. Changes in chemerin levels were positively associated with changes in adiponectin levels. The association between these changes might be related to chemerin's dual inflammatory and anti-inflammatory effects or insulin resistance and insulin sensitivity enhancing effects, depending on the metabolic conditions. Additional studies are needed to clarify the mechanisms that underlie the effects of adiponectin and chemerin.

Topics: Adiponectin; Adult; Anti-Obesity Agents; Appetite Depressants; Biomarkers; Body Mass Index; Chemokines; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Exercise; Female; Healthy Lifestyle; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Lactones; Male; Middle Aged; Obesity; Orlistat; Overweight; Waist Circumference; Weight Loss

Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.. We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.. We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m(-2) , respectively. Patients receiving orlistat lost, on average, 0.94 kg month(-1) (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month(-1) (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month(-1) .. Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Case-Control Studies; Cyclobutanes; Databases, Factual; Female; Humans; Lactones; Linear Models; Longitudinal Studies; Male; Middle Aged; Obesity; Orlistat; Primary Health Care; Time Factors; Treatment Outcome; United Kingdom; Weight Gain; Weight Loss

The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the 'real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom.. A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed.. Patients prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34-1.32).. Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

Topics: Anti-Obesity Agents; Appetite Depressants; Cohort Studies; Contraindications; Cyclobutanes; Female; Humans; Lactones; Male; Middle Aged; Myocardial Infarction; Obesity; Orlistat; Patient Safety; Patient Selection; Practice Patterns, Physicians'; Proportional Hazards Models; Risk Factors; Stroke; United Kingdom

To determine the impact of FDA safety communications regarding the weight loss medications sibutramine and orlistat.. The 2008 to 2011 pharmacy claims data from CVS Caremark were used to determine the effect of the relevant FDA warnings on (1) use of sibutramine and orlistat, (2) their rates of discontinuation, and (3) substitution to an alternate weight loss medication in the 3-month period following discontinuation.. The use of sibutramine, orlistat, or phentermine declined from 45 users per 100,000 Caremark enrollees in May 2008 to 24 users per 100,000 enrollees in December 2010. In the time series analyses of overall use of medications, a very small decline in the trend of use of sibutramine after the FDA communication (0.000002% per month decline after the communication; P < 0.001) was found. However, rates of discontinuation of sibutramine and orlistat were similar before and after relevant FDA communications (all P values >0.1 for both level and trend changes post-warning). Patients discontinuing sibutramine post-communication increased use of phentermine at a rate of 0.004% per month after discontinuation (P = 0.01).. From 2008 to 2010, use of prescription weight loss medications was low and declined over time. FDA communications regarding the safety of these medications had limited effect on use.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Cohort Studies; Cyclobutanes; Drug Utilization; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Phentermine; United States; United States Food and Drug Administration; Weight Loss; Young Adult

Obesity is a complex, multifactorial disease that, similarly to high blood pressure and diabetes, frequently requires pharmacological treatment with long-term use, suggesting that pattern of use could increase the rates of genetic damage. Among antiobesity drugs, meridia and orlistat act with completely different mechanisms of action. This study aimed to evaluate the mutagenic effect of meridia and orlistat on genetic material of mice by cytogenetic analysis, which included the micronucleus test and chromosomal aberration assay at two doses comparable to propose human therapeutic and double therapeutic doses. Results revealed that the total number of structural chromosomal aberrations in bone marrow cells, with gap, was significantly increased for the two drugs at therapeutic doses. The structural chromosomal aberrations involved breaks, gaps, deletions and fragments, and centric fusion. Chromosomal deletions and fragments were the most frequently increased types of structural chromosomal aberrations. At double therapeutic doses, the treated animals showed a high significant increase of total structural chromosomal aberrations with and without gaps for the two drugs. The frequency of micronucleus in mice treated with therapeutic doses was significantly increased for both drugs. The treated animals at double therapeutic doses showed a positive response for both drugs. In conclusion, treatment with these two drugs at therapeutic doses should be taken under precaution and contraindicated at double therapeutic doses, because the cytogenetic analysis of meridia and orlistat showed an adverse effect on genetic materials at therapeutic doses and a mutagenic effect at double therapeutic doses.

Topics: Animals; Anti-Obesity Agents; Bone Marrow Cells; Chromosome Aberrations; Cyclobutanes; Cytogenetic Analysis; Dose-Response Relationship, Drug; Lactones; Mice; Micronucleus Tests; Mutagenicity Tests; Mutagens; Orlistat

Topics: Anti-Obesity Agents; Cyclobutanes; Diabetes Mellitus, Type 2; Fluoxetine; Fructose; Humans; Lactones; Orlistat; Selective Serotonin Reuptake Inhibitors; Topiramate

Efficacy of weight loss and maintenance therapies in obesity is difficult to quantify due to continuous weight changes over time. We assessed a single exponential model of weight changes during selected non-surgical therapies of non-diabetic obese subjects. We analyzed published mean weight data from 6 studies of ≥12 weeks duration, with comparable treatment groups, and ≥4 weight measurements during very low carbohydrate or fat diets, or treatment with Lorcaserin, Sibutramine or Orlistat. We fit data to a single exponential model to estimate maximum predicted weight loss or regain and duration of weight loss or regain for each therapy. A single exponential is the appropriate model as determined by Kolmogorov-Smirnov, constant variance, and Durbin-Watson tests. Validity of parameter estimates was indicated by coefficients of variation <25%. Sensitivity analysis showed that weight regain at the end of the weight loss phase affected parameter estimates in some instances, with variations of weight loss of 0.2-0.7% of basal. Estimated weight loss and regain were similar to observed weight changes in all studies. The model could also be used to assess dose-response relationships. Estimates from the model were used to compare concurrent obesity regimens using 95% confidence intervals, taking into account pre-determined minimal clinically important differences. This exponential model may provide accurate estimates of maximum achievable weight loss or regain and optimal duration of efficacy for a variety of non-surgical weight loss and maintenance regimens from published mean weight data and may be useful to more accurately evaluate weight loss and maintenance regimens.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Body Mass Index; Body Weight; Cyclobutanes; Diet Therapy; Female; Humans; Lactones; Male; Models, Theoretical; Obesity; Orlistat; Sensitivity and Specificity; Treatment Outcome; Weight Loss

Many patients with polycystic ovary syndrome (PCOS) have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin, a novel adipokine that appears to preserve insulin sensitivity and glucose tolerance. The aim of the study was to assess serum vaspin levels in PCOS and the effects on vaspin levels of metformin or of weight loss. We studied 79 patients with PCOS and 50 healthy female volunteers. Normal weight patients with PCOS (n=25) were treated with metformin 850 mg bid for 6 months. Overweight/obese patients with PCOS (n=54) were prescribed a normal-protein, energy-restricted diet for 6 months; half of them were also given orlistat 120 mg tid and the rest were given sibutramine 10 mg qd. At baseline and after 6 months, serum vaspin levels and anthropometric, metabolic and hormonal features of PCOS were determined. Overall, patients with PCOS had higher vaspin levels than controls (p=0.021). Normal weight patients with PCOS had higher vaspin levels than normal weight controls (p=0.043). Vaspin levels were non-significantly higher in overweight/obese patients with PCOS than in overweight/obese controls. In normal weight patients with PCOS, metformin reduced vaspin levels non-significantly. In overweight/obese patients with PCOS, diet plus orlistat or sibutramine did not affect vaspin levels. Vaspin levels were independently correlated with body mass index in women with PCOS (p=0.001) and with waist circumference in controls (p=0.015). In conclusion, serum vaspin levels are elevated in PCOS but neither a small weight loss nor metformin affect vaspin levels significantly.

Topics: Adolescent; Adult; Body Mass Index; Cyclobutanes; Diet, Reducing; Female; Humans; Lactones; Metformin; Orlistat; Overweight; Polycystic Ovary Syndrome; Serpins; Weight Loss

In eight studies included in the present Cochrane review the effects of orlistat or sibutramine versus placebo on mortality, cardiovascular mortality and adverse events were investigated in obese people with hypertension. No studies with rimonabant fulfilled the inclusion criteria. The weight loss was larger in the groups treated with orlistat or sibutramine compared with placebo therapy. Orlistat reduced systolic and diastolic blood pressure more than placebo, while blood pressure increased during treatment with sibutramine. The studies were too small and of too short duration to allow an evaluation of the effect on cardiovascular mortality and morbidity.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Blood Pressure; Cardiovascular Diseases; Cyclobutanes; Evidence-Based Medicine; Humans; Hypertension; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Time Factors; Treatment Outcome; Weight Loss

Topics: Anti-Obesity Agents; Bridged Bicyclo Compounds, Heterocyclic; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

Post-marketing data on weight-loss medications in free living population are a necessary adjunct to data from clinical trials.. We conducted a population-based analysis of first-time medication users based on HMO pharmacy purchasing data serving > one million adults.. During 5 years, usage of orlistat and sibutramine more than doubled and rates were higher during the months May-Aug. As compared to non-users (n = 1,038,828), annual weight-loss drug users (n = 7175) had higher women proportion, body-mass-index (BMI), bariatric surgery history, and usage of diabetes, depression, and cardiovascular medications (p < 0.001 for all). Among users, men had higher BMI (34.4 kg/m(2) vs. 32.5 kg/m(2)), prevalence of diabetes (25.4% vs. 10.7%) and heart disease (14.2% vs. 3.5%) than women. Mean duration of purchasing weight-loss medications was 2.1 months for orlistat and 2.9 months for sibutramine. Fewer than 2% completed 12 months of weight-loss medication therapy. Among the 25% who continued to purchase at least 4 months, BMI (sub-group analysis) reduced from 33.02 kg/m(2) to 32.04 kg/m(2) (p < 0.001). In a multivariate model, long-term adherence (≥ 4 months) to weight-loss medications was associated with use of sibutramine vs. orlistat (OR = 2.08; 95%CI: 1.76-2.45), and prevalence of diabetes (OR = 1.20; 95%CI: 1.01-1.25). Age, gender, and baseline BMI were not associated with long-term adherence.. Usage of weight-loss drugs is higher among diabetes patients. However, the poor adherence to therapy is substantially below levels reported in clinical trials.

Topics: Adult; Analysis of Variance; Anti-Obesity Agents; Body Mass Index; Comorbidity; Cyclobutanes; Diabetes Mellitus; Female; Health Care Surveys; Health Maintenance Organizations; Humans; Insurance, Pharmaceutical Services; Israel; Lactones; Logistic Models; Male; Medication Adherence; Middle Aged; Obesity; Odds Ratio; Orlistat; Product Surveillance, Postmarketing; Registries; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Obesity causes a high disease burden in Australia and across the world. We aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy in Australia, and to assess its potential to reduce the disease burden due to excess body weight.. We constructed a multi-state life-table based Markov model in Excel in which body weight influences the incidence of stroke, ischemic heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis, post-menopausal breast cancer, colon cancer, endometrial cancer and kidney cancer. We use data on effectiveness identified from PubMed searches, on mortality from Australian Bureau of Statistics, on disease costs from the Australian Institute of Health and Welfare, and on drug costs from the Department of Health and Ageing. We evaluate 1-year pharmacological interventions with sibutramine and orlistat targeting obese Australian adults free of obesity-related disease. We use a lifetime horizon for costs and health outcomes and a health sector perspective for costs. Incremental Cost-Effectiveness Ratios (ICERs) below A$50 000 per Disability Adjusted Life Year (DALY) averted are considered good value for money.. The ICERs are A$130 000/DALY (95% uncertainty interval [UI] 93 000-180 000) for sibutramine and A$230 000/DALY (170 000-340 000) for orlistat. The interventions reduce the body weight-related disease burden at the population level by 0.2% and 0.1%, respectively. Modest weight loss during the interventions, rapid post-intervention weight regain and low adherence limit the health benefits.. Treatment with sibutramine or orlistat is not cost-effective from an Australian health sector perspective and has a negligible impact on the total body weight-related disease burden.

Topics: Anti-Obesity Agents; Australia; Cost-Benefit Analysis; Cyclobutanes; Drug Costs; Humans; Lactones; Obesity; Orlistat; Treatment Failure

The aim of the present study was to investigate to what extent patients using prescription antiobesity drugs (orlistat, sibutramine and rimonabant) concomitantly or concurrently used psychotropic drugs and analgesics and the association between this drug use and the patients' gender and age. An additional aim was to investigate the sequence of drug therapy among users of both antiobesity drugs and antidepressants or antipsychotics, respectively.. Data were retrieved from the Norwegian Prescription Database (NorPD). All patients who had an antiobesity drug (ATC code A08A) dispensed from a Norwegian pharmacy between January 2004 and December 2007 were included in the study.. One in four patients using antiobesity drugs had at least on one occasion used a psychotropic drug concomitantly. The most commonly used psychotropic drugs were anxiolytics/hypnotics/sedatives (17.7%) and antidepressants (14.7%). Analgesics were used by 36.2%. A significantly higher percentage of women used anxiolytics/hypnotics/sedatives (18.8% vs. 14.0%, p < 0.0005), antidepressants (16.1% vs. 9.5%, p < 0.0005), antipsychotics (4.0% vs. 2.9%, p < 0.0005) and analgesics (37.8% vs. 30.5%, p < 0.0005) concomitantly with antiobesity drugs when compared to men. One out of ten patients using sibutramine had at least on one occasion used an interacting drug concomitantly.. Use of psychotropic drugs and analgesics among patients using antiobesity drugs is extensive, especially among women. Clinicians prescribing sibutramine should be more aware of drug interactions with other prescribed drugs. There is still insufficient information on psychiatric disorders among these patients.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Analgesics; Anti-Obesity Agents; Child; Cyclobutanes; Databases, Factual; Drug Interactions; Female; Humans; Lactones; Male; Middle Aged; Norway; Orlistat; Piperidines; Practice Patterns, Physicians'; Psychotropic Drugs; Pyrazoles; Rimonabant; Sex Factors; Young Adult

Topics: Anti-Obesity Agents; Appetite Depressants; Benzazepines; Brain; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

Successful long-term weight loss maintenance can be achieved by various means. A combination of dietary and physical activity interventions, along with one or more behavioral approaches, has proven successful in some persons, as documented by the National Weight Control Registry, but is limited by adherence to a consistent weight loss regimen. Successful approaches to weight loss maintenance include consulting with a physician, nutritionist, or another support source; adhering to a stable diet with a limited variety of food; monitoring weight; eating breakfast; and exercising regularly. Long-term pharmacologic treatments for weight loss maintenance have been studied and were found to have modest success, with some weight regain typically reported. Sibutramine and orlistat are the two medications approved by the U.S. Food and Drug Administration with the potential to help patients achieve long-term weight loss maintenance. Bariatric surgery is another modality for accomplishing successful long-term weight loss maintenance in patients with morbid or complicated obesity. Its success is due in large part to better weight loss outcomes, more successful long-term weight loss maintenance, and remission of comorbid medical conditions.

Topics: Anti-Obesity Agents; Cyclobutanes; Diet, Reducing; Exercise; Gastric Bypass; Humans; Lactones; Obesity; Orlistat; Weight Loss

A clinical significant improvement in health-related quality of life (HRQOL) is one of the main goals of weight control.. To reveal the extent of weight loss on changes of HRQOL in obese Chinese.. A total of 119 motivated obese adults (BMI: 33.5 +/- 0.4 kg/m2) completed a 6-month weight loss intervention program by following either low calorie diet suggestions (LCDS; n=18), LCDS plus sibutramine (SG; n=27), LCDS plus orlistat (OG; n=41), or very low calorie diet (VLCD; n=33). Changes in body composition (TBF-410GS, Tanita Co., Tokyo, Japan) and HRQOL (36-item Short-Form (SF-36) questionnaire) were measured accordingly.. After 6-months, the greatest weight loss (p<0.001) was found in VLCD group (14.1 +/- 1.2 kg, 15.1%), followed by OG (10.6 +/- 0.9 kg, 11.5%), SG (9.6 +/- 1.3 kg, 10.2%) and LCDS alone (8.7 +/- 1.2 kg, 11.1%). The physical component score of SF-36 were significantly improved at 6-month follow-up (p<0.001), but not the mental component score. Improvements in general health score of SF-36 (Gamma mean: 6.1 +/- 2.8, p<0.05) were greater in females than males. Subjects with weight loss > or = 15 % had the greatest improvements in SF-36 scores whereas no changes in SF-36 scores were found with weight loss < 5%.. The extent, not the type of intervention, of weight loss is highly correlated with the favorable changes in HRQOL at 6-months. Weight loss above 5% of baseline values is necessary to show significant improvements in HRQOL in motivated obese Chinese.

Topics: Adolescent; Adult; Anti-Obesity Agents; Appetite Depressants; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Female; Health Status; Humans; Lactones; Male; Middle Aged; Motivation; Obesity; Orlistat; Quality of Life; Sex Characteristics; Taiwan; Weight Loss; Young Adult

* The antiobesity drugs sibutramine and orlistat are not licensed for use in children and adolescents in the UK or USA. * Clinical trials suggest antiobesity drugs are effective and well-tolerated in obese adolescents.. * Prescribing of unlicensed antiobesity drugs in children and adolescents has increased significantly in the past 8 years. * Most prescribed antiobesity drugs in children and adolescents are rapidly discontinued before patients can see clinical benefit, suggesting they are poorly tolerated or poorly efficacious.. The international childhood obesity epidemic has driven increased use of unlicensed antiobesity drugs, whose efficacy and safety are poorly studied in children and adolescents. We investigated the use of unlicensed antiobesity drugs (orlistat, sibutramine and rimonabant) in children and adolescents (0-18 years) in the UK.. Population-based prescribing data from the UK General Practice Research Database between 1 January 1999 and 31 December 2006.. A total of 452 subjects received 1334 prescriptions during the study period. The annual prevalence of antiobesity drug prescriptions rose significantly from 0.006 per 1000 [95% confidence interval (CI) 0.0007, 0.0113] in 1999 to 0.091 per 1000 (95% CI 0.07, 0.11) in 2006, a 15-fold increase, with similar increases seen in both genders. The majority of prescriptions were made to those >or=14 years old, although 25 prescriptions were made for children <12 years old. Orlistat accounted for 78.4% of all prescriptions; only one patient was prescribed rimonabant. However, approximately 45% of the patients ceased orlistat and 25% ceased sibutramine after only 1 month. The estimated mean treatment durations for orlistat and sibutramine were 3 and 4 months, respectively.. Prescribing of unlicensed antiobesity drugs in children and adolescents has dramatically increased in the past 8 years. The majority are rapidly discontinued before patients can see weight benefit, suggesting they are poorly tolerated or poorly efficacious when used in the general population. Further research into the effectiveness and safety of antiobesity drugs in clinical populations of children and adolescents is needed.

Topics: Adolescent; Age Distribution; Anti-Obesity Agents; Child; Child, Preschool; Cyclobutanes; Drug Prescriptions; Drug Utilization; Drugs, Investigational; Female; Humans; Infant; Lactones; Legislation, Drug; Male; Obesity; Orlistat; Practice Patterns, Physicians'; Risk Factors; Time Factors; Treatment Outcome; United Kingdom

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by parti

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Bradykinin; Cannabinoid Receptor Antagonists; Cannabinoids; Cyclobutanes; Diabetes Mellitus, Type 2; Double-Blind Method; Economics, Pharmaceutical; Humans; Lactones; Lipase; Meta-Analysis as Topic; Obesity; Orlistat; Piperidines; Practice Guidelines as Topic; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Risk Factors; Time Factors; Weight Loss

Obesity is a major health problem in the United States and many other countries because of its high prevalence and causal relationship with serious medical comorbidities. The therapeutic options currently available to help obese patients lose weight are: (1) therapeutic lifestyle change (behavioral, dietary, and physical activity modification); (2) pharmacotherapy; and (3) bariatric surgery. Lifestyle modification is the first therapeutic choice; however, achieving a successful long-term weight loss with lifestyle intervention alone is difficult. There is increasing interest, therefore, in the use of pharmacotherapy and surgery to treat obesity. Although there are a number of antiobesity medications available, the only medications approved in the United States for long-term treatment of obesity are sibutramine and orlistat. Use of these medications results in 3% to 5% more weight loss compared with placebo after 1 year. Bariatric surgery is an effective weight loss option for obese patients, but it is restricted to patients who are considered morbidly obese (ie, with a body mass index [BMI] > or =40 kg/m(2) or a BMI of 35-39.9 kg/m(2) with > or =1 severe obesity-related medical complication).

Topics: Anti-Obesity Agents; Bariatric Surgery; Cannabinoid Receptor Modulators; Cardiovascular Diseases; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat; Risk Factors; Weight Loss

Overweight and obesity are major factors contributing to the development of type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). In addition to the many physical and metabolic consequences of obesity, there are also mental health consequences, in particular, the risk for depression. Depression can lead to poor self-care, poor treatment compliance, and possible increased morbidity and mortality from such illnesses as type 2 DM and CVD. Lifestyle modification for the treatment of overweight and obesity is rarely successful over the long term, and use of surgery is limited by eligibility criteria; therefore, researchers and clinicians continue to explore pharmacotherapy, with intense efforts being directed toward the development of agents that, optimally, will reduce weight and simultaneously reduce or eliminate modifiable cardiovascular and metabolic risk factors. Among the promising new agents are the CB(1) receptor antagonists. These agents target receptors of the endocannabinoid system, a neuromodulatory system recently found to influence energy balance, eating behavior, and metabolic homeostasis via central and peripheral mechanisms. In animal and clinical studies, antagonism of CB(1) receptors has resulted in meaningful weight loss and improvement of lipid and glycemic profiles. Thus, these agents may provide a rational and effective approach for the management of not only overweight and obesity but also their metabolic and cardiovascular sequelae.

Topics: Amides; Anti-Obesity Agents; Cannabinoid Receptor Modulators; Cyclobutanes; Depression; Endocannabinoids; Humans; Lactones; Life Style; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Pyridines; Rimonabant; Risk

To study the associations between weight loss with sibutramine and orlistat with psychological aspects that may interact with patients' response to these drugs.. A total of 478 obese patients with a mean body mass index of 42 +/- 12 kg/m(2) gave self-reported, retrospective data on different types of previous weight loss treatments (sibutramine and orlistat, and Weight Watchers used as a control condition) including the amount of weight lost with these treatments, eating behaviour (Dutch Eating Behaviour Questionnaire) and personality (NEO Personality Inventory - Revised).. Greater weight loss with sibutramine was associated with lower levels of restrained eating and higher levels of 'neuroticism', in particular 'anxiety' and 'depression'. Greater weight loss with orlistat was associated with aspects of the personality dimension 'conscientiousness' (e.g. 'order' and 'deliberation').. Sibutramine may exert its greatest effect in patients whose eating is a 'natural' response to hunger rather than regulated by cognitions and conscious controls. Patients with low levels of restraint could be more sensitive to the satiety-enhancing effect of sibutramine. They may be able to reduce their food intake without cognitive interference and/or start to control their eating most radically in response to enhanced satiety. Enhanced satiety may also help patients withstand a wish to eat triggered by psychological distress. Possible central nervous system effects on mood could also have reduced eating, which was related to distress. The administration regimen of orlistat is more demanding, requiring greater adherence. This can account for the finding that personality attributes such as conscientiousness are important for success.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Appetite; Appetite Depressants; Body Weight; Cyclobutanes; Diet, Reducing; Feeding Behavior; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Personality; Retrospective Studies; Self Disclosure; Treatment Outcome; Weight Loss

To investigate how the antiobesity drugs orlistat and sibutramin are prescribed in relation to the approved indications and the Swedish subsidiary rules.. Anonymous survey to prescribers of a random sample of 2000 out of 20,000 prescription of orlistat and sibutramin.. The response rate was around 65%. About half of the patients were not treated in accordance with the approved indications and a fourth of the patients prescribed sibutramin had one or several contraindications to the drug. The subsidiary rules were not followed in the majority of cases.. Deviation from the approved indications and subsidiary criteria of orlistat and sibutramin is a question of waste of medical and economic resources. Prescribing of sibutramin to patients with contraindications is a serious health hazard.

Topics: Anti-Obesity Agents; Appetite Depressants; Contraindications; Cyclobutanes; Guideline Adherence; Humans; Lactones; Medication Errors; Obesity; Orlistat; Practice Patterns, Physicians'; Risk Factors; Surveys and Questionnaires; Sweden; Weight Loss

Orlistat and sibutramine are widely prescribed antiobesity agents that are approved for 2 years of continuous use. Previous 1-4-year randomized, placebo-controlled trials of these drugs have reported average weight losses of <5 kg, significant adverse effects and attrition rates of up to 60%. The objective of this study was to determine the long-term persistence with orlistat and sibutramine therapy outside a clinical trial setting.. Population-based administrative data from British Columbia, Canada, were used to create an inception cohort of orlistat and sibutramine users and determine the 2-year persistence with therapy.. Persistence with therapy at 2 years. Drug discontinuation was defined as the failure to refill a prescription within 120 days. Patients discontinuing therapy were censored at the 60-day mark.. Nearly 17 000 users of orlistat and 3500 users of sibutramine were identified. For both orlistat and sibutramine, 1-year persistence rates were <10% and 2-year persistence rates were 2%.. This population-based, retrospective cohort analysis demonstrated very poor long-term persistence rates with orlistat and sibutramine and discontinuation rates that were much higher than those reported in clinical trials.

Topics: Adult; Anti-Obesity Agents; British Columbia; Cyclobutanes; Epidemiologic Methods; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Patient Compliance; Time Factors

To report the trends in the use and costs of anti-obesity medications in England from 1998 to 2005.. We analysed data on all community anti-obesity drug prescriptions in England collated by the prescription cost analysis system.. Between 1998 and 2005, Orlistat prescriptions rose 36-fold from 17,880 to 646,700 and total cost increased by over 35-fold. Sibutramine prescriptions rose from 2001 to 2005 from 53,393 to 227,000, a 4-fold increase. Although prescriptions of Orlistat and Sibutramine have increased substantially since they were first introduced, the rate of growth decreased substantially in recent years until 2005, when a significant increase in the number and cost of prescriptions for orlistat occurred yet again.. We found a large increase in the use and costs of anti-obesity prescriptions, consistent with the increased awareness of obesity amongst health care professionals and the public. Despite this large increase, there are still no head-to-head studies at a national level that directly compare all anti-obesity medication in use in the UK.

Topics: Anti-Obesity Agents; Cyclobutanes; Drug Costs; Drug Therapy; England; Humans; Lactones; Obesity; Orlistat; Prevalence

Topics: Anti-Obesity Agents; Bariatric Surgery; Cyclobutanes; Disease Outbreaks; Humans; Lactones; Obesity; Orlistat; Pharmacists; Professional Role

Between July 2004 and June 2005, a cross-sectional study was performed to determine the prevalence and patterns of anti-obesity medicine use among subjects seeking obesity treatment in Taiwan. Eighteen obesity outpatient clinics were selected via a random stratified sampling method and 1,060 first-visit clients (791 females and 269 males) aged above 18 years were enrolled and then completed a self-administered questionnaire. The prevalence of anti-obesity medicine use was 50.8%; more females than male used anti-obesity medicines (53.6% vs. 42.4%). Of the 1,060 subjects, 17.1% had used orlistat, 21.1% had taken sibutramine, and 18.3% had utilized un-proven drugs such as cocktail therapy and other anti-obesity drugs. Furthermore, 23.6% and 22.4% of subjects indicated that they concurrently used Chinese herbal preparations and dietary supplements, respectively. Logistic regression analyses demonstrated that the odds ratio (OR) for anti-obesity medicine use was substantially higher in females (OR, 1.9; 95% CI, 1.3-2.6), those aged 18-24 years (OR, 1.6; 95% CI, 1.0-2.6), those with a body mass index (BMI) >35 kg/m2 (OR, 3.4; 95% CI, 2.1-5.7) and respondents concurrently using Chinese herbal preparations (OR, 1.7; 95% CI, 1.2-2.4) and dietary supplements (OR, 2.2; 95% CI, 1.6-3.1). In conclusion, the prevalence of anti-obesity drugs use is high among Taiwanese adults before they seek obesity treatment. Young, obese females, and those who had taken Chinese herbal preparations/dietary supplements had a high likelihood to report using anti-obesity medicines. Use of unproven weight-loss drugs is common and warrants further investigation.

Topics: Adolescent; Adult; Age Distribution; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Confidence Intervals; Cross-Sectional Studies; Cyclobutanes; Dietary Supplements; Drug Utilization; Evidence-Based Medicine; Female; Humans; Lactones; Male; Middle Aged; Obesity; Odds Ratio; Orlistat; Outpatient Clinics, Hospital; Phytotherapy; Prevalence; Sex Distribution; Surveys and Questionnaires; Taiwan; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Fluoxetine; Follow-Up Studies; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Factors; Weight Loss

Observational cohort studies were conducted using prescription-event monitoring (PEM) to examine the safety profiles of the anti-obesity agents orlistat and sibutramine. Adverse events reported as case reports were also evaluated to determine whether these events were also identified by PEM.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) in England for orlistat or sibutramine. Patient demographic and clinical event information, including reasons for stopping and adverse drug reactions, were requested on questionnaires posted to GPs at least 6 months after the first prescription for individual patients. Event incidence densities (IDs) (number of first reports of event/1000 patient-months treatment) were calculated for month 1 (ID(1)) and months 2-3 (ID(2-3)). Published case reports were identified by searching Medline and Embase.. The cohorts comprised 16,021 and 12,336 patients prescribed orlistat and sibutramine, respectively. Both cohorts had a median age of 45 years, and approximately 80% were female. The most common reason for stopping orlistat within 3 months was diarrhea (332 patients; 2.1% cohort), and for stopping sibutramine it was hypertension (203 patients; 1.6%). Clinical events significantly associated with taking orlistat were mainly gastrointestinal and those for sibutramine included central nervous system effects, nausea/vomiting, palpitation, and sweating. We identified 8 published case reports for orlistat and 10 for sibutramine that had equivalent or similar events assessed as causally related in the PEM studies.. The PEM studies highlighted different adverse event profiles for orlistat and sibutramine that were consistent with their distinct pharmacological mechanisms and other published information.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Adverse Drug Reaction Reporting Systems; Anti-Obesity Agents; Appetite Depressants; Cohort Studies; Cyclobutanes; Drug Monitoring; England; Female; Humans; Lactones; Male; Middle Aged; Nausea; Obesity; Orlistat; Pregnancy; Pregnancy Outcome; Sweating; Treatment Outcome; Vomiting

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Depression; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Lactones; Obesity, Morbid; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Suicide; Weight Loss

Topics: Anti-Obesity Agents; Cyclobutanes; Eating; Female; Humans; Lactones; Obesity; Orlistat; Overweight; Weight Loss

Prompt identification of responders to non-surgical therapy is of utmost importance in attempting medical treatment in patients with clinically severe obesity before indication of bariatric surgery. The objectives of the present study were to assess the outcome at 1 year of morbidly obese patients undergoing a weight-loss medical programme and to detect baseline predictors of a loss >or=10 % of initial weight at the end of the follow-up. A longitudinal, prospective study of a cohort of morbidly obese patients (n 182; females 78 %; age 40.5 (SD 11.5) years; BMI 45.4 (SD 6.0) kg/m(2)) enrolled in a 1-year obesity-management programme based on lifestyle changes and pharmacological therapy. Significant laboratory and clinical variables were included in a binary logistic regression model in order to identify baseline independent factors for the prediction of a successful outcome in the programme. At 12 months of follow-up, twenty-one subjects (11.5 % of the initial cohort) had lost >or=10 % of baseline weight. A high serum folic acid level was the only independent predictor of weight loss at 1 year. A rise of 1 ng/ml in serum folate increased the chance of success by 28 % (adjusted odds ratio 1.28; 95 % CI 1.04, 1.58). We concluded that a medical-management programme of morbid obesity obtained limited results at 1 year, in agreement with other intervention studies. Serum folate may be useful as a pre-treatment predictor of response to a medical-management programme in patients with morbid obesity. Patients with low basal serum folate levels probably should be urged to change unhealthy eating patterns.

Topics: Adolescent; Adult; Anti-Obesity Agents; Appetite Depressants; Biomarkers; Cyclobutanes; Eating; Female; Ferritins; Folic Acid; Humans; Lactones; Life Style; Male; Middle Aged; Obesity, Morbid; Orlistat; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Weight Loss

In this clinical observation, we make a small summary of the current state of pharmacological treatment of obesity. The interest in the use of drugs in the treatment of obesity has grown in recent years, upon our knowledge of the biological basis of obesity having increased, and also because non-pharmacological treatments have not succeeded stopping the constant increase of obesity incidence in western countries. Only two drugs are currently approved by the European Agency of the Drug and the FDA (Food and Drug Administration, United States) for the treatment of long-term obesity: sibutramine and orlistat. Pharmacological treatment of obesity should be considered in obese patients (BMI > 30) or overweight (BMI > 27) in presence of comorbidities as diabetes mellitus, hypertension, dyslipemias (7.8); this must not be used as an isolated treatment but together with other basic therapies: diet, physical exercise and psychological support.

Topics: Anti-Obesity Agents; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

Topics: Anti-Obesity Agents; Appetite Depressants; Cannabinoids; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Lactones; Male; Middle Aged; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant

Obesity and overweight are affecting increasing numbers of Canadians and have received considerable amounts of medical, governmental, and media attention in recent years. This study sought to determine whether this rise in prevalence and awareness has resulted in an increased frequency of obesity and overweight-related office visits or antiobesity drug prescriptions over the past 5 years.. Data from IMS Health Canada were used to derive nationally representative estimates of trends in the annual number of obesity and overweight-related office visits (1999 to 2003) and the quarterly prescription volume of antiobesity drugs (July 1998 to March 2003) in Canada.. The number of obesity and overweight-related office visits increased by 20% between 1999 and 2000 but then remained constant. The number of antiobesity drug prescriptions peaked in 2001 and has since declined, with parallel trends being observed for all individual agents. In contrast, the overall frequency of office visits and drug prescriptions in Canada (for any reason) progressively increased over the study period. Middle-aged women were the most common type of patient to seek physician advice regarding obesity, and general practitioners were the most common type of physician visited.. Increases in the prevalence and awareness of obesity have not resulted in major increases in office visits or drug prescriptions for this condition over the past 5 years. A number of patient, physician, and drug-related factors may explain these results, which are likely a reflection primarily of the current lack of effective weight loss strategies for obese individuals.

Topics: Adult; Aged; Anti-Obesity Agents; Canada; Cyclobutanes; Drug Prescriptions; Female; Humans; Lactones; Male; Middle Aged; Obesity; Office Visits; Orlistat; Overweight; Prevalence

Modest weight loss if maintained is associated with significant metabolic benefits and reduction in cardiovascular risk. Adipose tissue secretes cytokines believed to contribute to the pathogenesis of insulin resistance and cardiovascular risk. We therefore observed the effect of modest weight loss on serum adipocytokines and their relationship with changes in anthropometric and metabolic parameters within a period of 6 months in the setting of a routine obesity hospital clinic after various medical treatments. In this prospective, nonrandomized, nonblinded observational study, patients were first given treatment (sibutramine or orlistat) as decided by the treating clinician and then allocated into 1 of 2 groups according to the treatment prescribed. The first group included 21 Caucasian nondiabetic female subjects, with a mean (+/-SD) age of 43 +/- 11 years and a mean body mass index (BMI) of 46 +/- 8.6 kg/m(2); subjects were treated with sibutramine 10 or 15 mg/d for weight loss. The second group included 20 Caucasian nondiabetic female subjects, mean age 42 +/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced after 1 month on a low-fat (5%) after medical treatment in a routine obesity hospital clinic is associated with improvements in insulin sensitivity and lipid profile. Modest weight loss is also associated with

Topics: Abdomen; Adipocytes; Adult; Anti-Obesity Agents; Appetite Depressants; Body Constitution; Cyclobutanes; Cytokines; Female; Humans; Lactones; Obesity; Orlistat; Prospective Studies; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Evidence-Based Medicine; Humans; Lactones; Obesity; Obesity, Morbid; Orlistat; Treatment Outcome; Weight Loss

Topics: Adolescent; Adult; Anti-Obesity Agents; Antidepressive Agents; Appetite Depressants; Body Mass Index; Comorbidity; Cross-Over Studies; Cyclobutanes; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Energy Intake; Female; Humans; Lactones; Lipase; Male; Mental Disorders; Middle Aged; Obesity; Orlistat; Randomized Controlled Trials as Topic; Sex Factors; Time Factors; Weight Loss

Topics: Agouti-Related Protein; alpha-MSH; Animals; Anti-Obesity Agents; Appetite; Arcuate Nucleus of Hypothalamus; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Energy Intake; Ghrelin; Humans; Hunger; Intercellular Signaling Peptides and Proteins; Lactones; Leptin; Mice; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Obesity; Orlistat; Peptide Fragments; Peptide Hormones; Peptide YY; Phentermine; Proteins; Receptors, Corticotropin; Receptors, Melanocortin; Weight Loss

Topics: Animals; Anti-Obesity Agents; Ciliary Neurotrophic Factor; Cyclobutanes; Drug Evaluation; Drugs, Investigational; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Recombinant Proteins; Rimonabant; United States; United States Food and Drug Administration

Topics: Anti-Obesity Agents; Appetite Depressants; Contraindications; Cyclobutanes; Diet, Reducing; Exercise; Humans; Lactones; Obesity; Orlistat; Time Factors

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Blood Glucose; Body Mass Index; Cyclobutanes; Diabetes Complications; Diabetes Mellitus; Humans; Hypertension; Lactones; Obesity; Orlistat; Risk Factors; Time Factors

Topics: Anti-Obesity Agents; Cyclobutanes; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Lactones; Metformin; Middle Aged; Obesity; Orlistat; Selective Serotonin Reuptake Inhibitors; Sulfonylurea Compounds

These consensus-based recommendations emphasize the practical implementation of nutritional advice for people with diabetes, and describe the provision of services required to provide the information. Important changes from previous recommendations include greater flexibility in the proportions of energy derived from carbohydrate and monounsaturated fat, further liberalization in the consumption of sucrose, more active promotion of foods with a low glycaemic index, and greater emphasis on the provision of nutritional advice in the context of wider lifestyle changes, particularly physical activity. Monounsaturated fats are now promoted as the main source of dietary fat because of their lower susceptibility to lipid peroxidation and consequent lower atherogenic potential. Consumption of sucrose for patients who are not overweight can be increased up to 10% of daily energy provided that this is eaten in the context of a healthy diet and distributed throughout the day [corrected]. Evidence is presented for the effectiveness of advice provided by trained dieticians. The increasing evidence for the importance of good metabolic control and the growing requirement for measures to prevent Type 2 diabetes in an increasingly obese population will require major expansion of dietetic services if the standards in National Service Frameworks are to be successfully implemented.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Asian People; Body Composition; Child; Cyclobutanes; Diabetes Mellitus; Diet; Dietary Services; Exercise; Feeding and Eating Disorders; Female; Glycemic Index; Humans; Insulin; Lactones; Male; Middle Aged; Nutritional Physiological Phenomena; Orlistat; Patient Education as Topic; Pregnancy; Pregnancy in Diabetics; Selective Serotonin Reuptake Inhibitors; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Clinical Trials as Topic; Contraindications; Cyclobutanes; Exercise; Humans; Hypertension; Lactones; Life Style; Lipase; Obesity; Orlistat; Risk Factors; Time Factors; Weight Loss

Topics: Appetite Depressants; Body Weight; Cyclobutanes; Humans; Lactones; Orlistat; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

The health risks of obesity include the development of comorbid conditions and increased overall mortality. Obesity increases health-related costs for both patients and the healthcare system and significantly affects workforce productivity through increased absenteeism and higher health and insurance payments for employers. Discrimination against obese individuals exists in the workplace and in various social contexts. Obesity is a chronic condition with complex, multiple causes involving physiologic, genetic, and behavioral components, all of which must be addressed for successful treatment. Traditional treatment options include diet, exercise, and behavior modification, but recently, pharmacotherapy has been incorporated as an effective and safe adjunct for long-term treatment of obesity. Additionally, bariatric surgery is an option for selected morbidly obese individuals. Weight losses of only 5% to 10% of initial body weight confer proven clinical benefits. Such modest weight losses can be achieved and maintained within a supportive environment provided in a primary care practice.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Cardiovascular Diseases; Cyclobutanes; Humans; Lactones; Obesity; Orlistat; Primary Health Care; Risk Assessment; Weight Loss

A variety of treatments--behavior-modification programs, reduced-calorie diets, and pharmacotherapy--are available to treat obesity and can be effective in producing the 5% to 10% weight loss now recommended as a primary goal of therapy. The mechanisms of action of medication and behavior modification are different and complementary. Behavior therapy helps obese individuals to adopt a diet reduced in calories and fat and to increase daily physical activity; pharmacotherapy assists by modifying internal cues that control eating. Recent clinical studies indicate that combining these approaches is likely to be the most effective treatment for obese patients. Regardless of the approach selected, long-term care is required to achieve and maintain weight loss.

Topics: Anti-Obesity Agents; Appetite Depressants; Behavior Therapy; Body Mass Index; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Exercise; Feeding Behavior; Humans; Lactones; Life Style; Nutritional Status; Obesity; Orlistat; Weight Loss

Obesity is a significant health problem in the United States today and is associated with increased risk of cardiovascular disease, diabetes, and other chronic conditions. Weight loss improves obesity-related health complications and may decrease their incidence as well.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Cyclobutanes; Feeding Behavior; Health Behavior; Humans; Lactones; Life Style; Nutritional Status; Obesity; Orlistat; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Counseling; Cyclobutanes; Diet, Reducing; Drug Therapy, Combination; Exercise; Female; Humans; Lactones; Leptin; Life Style; Obesity; Orlistat; Patient Education as Topic; Patient Selection; Primary Health Care; United States; Weight Loss; Women's Health

Topics: Adult; Anti-Obesity Agents; Child; Cyclobutanes; Female; Humans; Insurance, Pharmaceutical Services; Lactones; Male; Obesity; Orlistat; Spain

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Life Style; Obesity; Orlistat; Patient Education as Topic; Physician-Patient Relations

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Obesity; Orlistat

Obesity, and its associated complications, is one of the most costly diseases in modern civilisations. Dieting alone rarely gives good long-term results. The effect of the combination of nutritional education and moderately intensive physical exercise on the evolution of weight and Body composition has been analysed by bio-impedancemetry over a one-year period. Patients could be divided into four groups: patients lost after the 3-week nutritional course, patients neither dieting nor exercising, patients dieting and patients both dieting and exercising. The results for the four groups were the following: undeterminably, 5% loss compared to initial weight (and nearly 10% compared to reported maximum weight). 10% loss and 15% loss over one year. In the last group, Body composition showed a relative increase in muscle mass, which explains the lack of a drop in basal metabolic rates seen in the diet-alone group. This maintained metabolic rate probably prevented patients from weight cycling (yo-yo phenomenon). This result can be compared to other life-style changing studies or pharmacological treatments (Orlistat, sibutramine) of obesity, which resulted in an approx. 10% weight reduction.

Topics: Anti-Obesity Agents; Body Composition; Body Weight; Cyclobutanes; Diet, Reducing; Electric Impedance; Exercise; Female; Humans; Lactones; Male; Middle Aged; Nutritional Physiological Phenomena; Obesity; Orlistat; Patient Compliance; Patient Education as Topic; Retrospective Studies; Weight Loss

Obesity is one of the pathologies with ever-increasing prevalence in modern societies. Its occurrence is strongly associated with increased risk of developing diabetes mellitus, atherosclerosis, hypertension, stroke, heart and respiratory failure, breast, prostate and gut cancer, gall stones, arthropathy. Obesity is common in Polish population. Obesity treatment is difficult and frustrating. It consists of several parts like diet, increased physical activity, lifestyle changes, drug therapy and surgery. However, obesity treatment is very often a failure, mostly because of discouraging long-term results and the necessity of intensive patient's involvement in the therapy. For many patients and doctors weight-decreasing agents look promising. The groups of anti-obesity drugs are presented in the article, with special reference to serotoninergic agents and intestinal lipase inhibitors. The prospects for new anti-obesity agents are discussed. Nevertheless, despite intensive research on obesity, we are still waiting for the development of an effective and safe drugs helping lose weight.

Topics: Adult; Animals; Anti-Obesity Agents; Chlorphentermine; Cyclobutanes; Dexfenfluramine; Dopamine Agonists; Ephedrine; Fluoxetine; Humans; Lactones; Mazindol; Obesity; Orlistat

Topics: Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Double-Blind Method; Drug Therapy, Combination; Enzyme Inhibitors; Fees, Pharmaceutical; Humans; Intestinal Absorption; Lactones; Lipase; Obesity; Orlistat; Phentermine

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Body Weight; Cyclobutanes; Enzyme Inhibitors; Humans; Lactones; Obesity; Obesity, Morbid; Orlistat; Patient Selection; Weight Loss

Sibutramine and Orlistat are suitable "supporting drugs" for use in patients trying to lose weight. Orlistat reduces the absorption of fat from the intestine by about one-third. Over the long term too, the weight loss achieved under Orlistat (9%) has been greater than that seen under placebo (6.5%). Increased fat losses via the stools are associated with side effects and abandonment of treatment. Sibutramine inhibits the uptake of serotonin and noradrenaline in the synaptic gap, thus enhancing the CNS effects of these two transmitters, and prolonging the sensation of satiety. The most common side effects of sibutramine are dry mouth, headache and fatigue. The effects of sibutramine on weight reduction are similar to those of orlistat. For both drugs, the indications have been defined, and in the case of sibutramine, interactions with other medications have to be taken into account.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Contraindications; Cyclobutanes; Drug Interactions; Humans; Lactones; Obesity; Orlistat; Treatment Outcome

Topics: Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Cyclobutanes; Diet; Humans; Lactones; Obesity; Orlistat; Time Factors; Treatment Outcome; Weight Loss

Topics: Adrenergic Agonists; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Lipase; Obesity; Orlistat; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists