orlistat and Weight-Loss

The study aim was to review the economic evaluation literature of commercially available and effective nonsurgical weight-loss interventions to investigate whether there is evidence to support claims of cost-effectiveness (i.e., good value for money) or cost savings (i.e., a positive return on investment).. Relevant databases were systematically reviewed to identify economic evaluations of commercially available weight-loss products and services shown to result in clinically significant weight loss. Five weight-loss medications (orlistat, liraglutide, naltrexone-bupropion, semaglutide, and phentermine-topiramate), two meal replacement programs (Jenny Craig, Optifast), and one behavioral intervention (Weight Watchers [WW]) that met inclusion criteria were identified. After screening, 32 relevant comparisons of cost-effectiveness or cost savings across 20 studies were identified.. Ten of twenty pharmaceutical comparisons showed evidence of cost-effectiveness based on established thresholds. Four of twelve nonpharmaceutical comparisons provided evidence of cost-effectiveness, and five made claims of cost savings. However, methodological concerns cast doubt on the robustness of these claims.. Evidence of cost-effectiveness for commercially available, evidence-based, nonsurgical weight-loss interventions is mixed. There is no evidence for cost-saving weight-loss medications and only weak evidence for behavioral and weight-loss interventions. Results provide a call to action to generate more robust evidence of the economic value proposition for these interventions.

Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Humans; Liraglutide; Orlistat; Weight Loss

The global incidence of childhood obesity is increasing. Currently, there are only few established drugs for treating adolescent obesity. Randomized clinical trials (RCTs) comparing pharmacological interventions in children with obesity are scarce; therefore, we aimed to analyze the relative efficacy and adverse reactions of these drugs and compare the effects of each drug on body mass index (BMI).. This meta-analysis focused on the slimming effect, safety, and correlation of metformin, orlistat, exenatide, liraglutide, and topiramate in children with obesity. Several international databases were searched and clinical trials on the treatment of obesity in children in which the drug was administered for ≥ 6 months were included. Changes in BMI before and after treatment were analyzed using a Bayes framework, and the surface under the cumulative ranking was calculated.. Of 2102 relevant articles retrieved, 21 RCTs were included in the study. Compared to other drugs, liraglutide reduced BMI the most in children with obesity. However, it was most associated with drug withdrawal due to adverse events while topiramate was least.. Liraglutide had a higher probability of achieving clinically significant weight loss compared with other drugs while topiramate was superior in safety.

Topics: Adolescent; Anti-Obesity Agents; Child; Exenatide; Humans; Liraglutide; Metformin; Obesity; Orlistat; Topiramate; Weight Loss

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

Topics: American Heart Association; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Exercise; Humans; Hypertension; Obesity; Orlistat; Phentermine; United States; Weight Loss

Obesity and its comorbidities represent a worldwide growing health challenge. In Germany, at least 15 million people are suffering from this disease. To date, lifestyle modification is the most frequently used treatment modality, but offers only limited success concerning both the extent and the sustainability of weight loss, while surgical interventions are restricted to people with severe obesity (body mass index ≥40 kg/m. Adipositas und ihre Begleit- und Folgeerkrankungen stellen ein weltweit wachsendes Gesundheitsproblem dar. In Deutschland sind mindestens 15 Mio. Menschen von dieser Erkrankung betroffen. Die bisherigen Therapiekonzepte zur Lebensstiländerung zeigen bei den meisten Betroffenen nur begrenzte Wirksamkeit, was Ausmaß und Nachhaltigkeit der Gewichtsabnahme betrifft. Die wirksameren chirurgischen Interventionen müssen dagegen Menschen mit extremer Adipositas (Body-Mass-Index ≥40 kg/m

Topics: Anti-Obesity Agents; Humans; Illicit Drugs; Obesity; Orlistat; Weight Loss

As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism.. Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.

Topics: Animals; Anti-Obesity Agents; Benzazepines; Bupropion; Humans; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Hyperuricemia increases the risk of gout and cardiovascular diseases. Obesity increases the risk of hyperuricemia while weight loss (>5 kg) has been reported to decrease urate. The effects of orlistat on serum uric acid (SUA) are still controversial. The aim of this meta-analysis was to evaluate the influence of orlistat on SUA levels in adults.. Relevant studies, published up to May 2020, were searched systematically through PubMed/Medline, Scopus and Google Scholar. All relevant randomised controlled clinical trials were included. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis and meta-regression were also carried out.. Overall 7 trials (9 datasets) that enrolled 1786 subjects were included. Orlistat showed in a significant change in SUA level (Difference in means: -17.661 μmol, 95% CI: -31.615 to -3.707, P = .01). A low heterogeneity observed across the studies (I. We found a significant reduction in SUA following orlistat therapy in adults.

Topics: Adult; Gout; Humans; Hyperuricemia; Orlistat; Randomized Controlled Trials as Topic; Uric Acid; Weight Loss

Topics: Adult; Anti-Obesity Agents; Humans; Orlistat; Phentermine; State Medicine; Weight Loss

The increase in global obesity rates over the past three decades has been remarkable, a true epidemic, both in developed and in developing countries. The projections, based on current trends, suggest an increase in the prevalence of obesity at 60% in adult men, 40% in adult women and 25% in children in 2050. Given the limitations of lifestyle and surgery interventions bariatric, drug therapy approaches for the treatment of obesity, therefore become important options.. The purpose of this review is a review of the literature, based on research on MEDLINE until 2019, on the possible pharmacological options in the treatment of obesity.. Currently, the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multitarget approach and include phentermine/topiramate and naltrexone/bupropion. All the approved drugs showed, in the different studies, a weight reduction of at least 5%, compared to placebo, in 52 weeks of observation. Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. Liraglutide and naltrexone-bupropion had the lowest rates of therapy discontinuation due to adverse events.. The drugs, associated with the standard diet and/or exercise protocols, represent a good therapeutic opportunity to allow not only weight loss but also to reduce the risk of developing diseases caused by obesity, particularly cardiovascular diseases, and to maintain the set objectives over time. However, future research on the pharmacological treatment of obesity should encourage greater personalization of therapy, given the differences in safety, efficacy and response to therapy, in the different subpopulations of patients with obesity.

Topics: Anti-Obesity Agents; Bupropion; Epidemics; Global Health; Humans; Liraglutide; Naltrexone; Obesity; Orlistat; Precision Medicine; Weight Loss

Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.

Topics: Anti-Obesity Agents; Benzazepines; Humans; Orlistat; Phentermine; Weight Loss

Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others.. Herein, the authors review the most commonly used FDA approved medications for the treatment of obesity, describing their mechanism of action, and the efficacy and safety of the medications as seen in recent studies, particularly in patients with CVD.. In the population of patients with obesity and CVD, the medications orlistat, lorcaserin and liraglutide are considered the most appropriate options for their treatment, in terms of safety. Sympathomimetic medications, such as phentermine, should be avoided in this group. The recent CAMELLIA-TIMI 61 trial supports the safety of lorcaserin in patients with CVD. Until there are more studies, it is reasonable to extrapolate the findings of the LEADER trial, which found improved CV outcomes in subjects with type 2 diabetes taking liraglutide, to the population of nondiabetic patients being treated for obesity. Further cardiovascular outcomes trials (CVOT) are needed to assess the safety of other pharmacotherapeutic options for weight loss.

Topics: Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Liraglutide; Obesity; Orlistat; Phentermine; Weight Loss

Obesity and high blood pressure (BP) are strongly related and weight loss is mightily associated with a significant BP decrease. The aim of the present meta-analysis was to evaluate and quantify the BP decrease associated with orlistat use in randomized controlled trials. The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to June 05, 2017, to identify randomized controlled trials investigating the impact of orlistat on blood pressure. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference and 95% confidence interval as summary statistics. Meta-regression and leave-one-out sensitivity analyses were performed to assess the modifiers of treatment response. Our meta-analysis included 27 randomized controlled clinical trials which comprehended overall 8150 subjects (4419 in the orlistat group and 3731 in the control one). We observed a statistically significant decreasing effect of orlistat on both systolic BP (-1.15 mmHg [-2.11, -0.19]) and diastolic BP (-1.07 mmHg [-1.69, -0.45]), regardless of its dosage. Significant associations were found between changes in systolic BP and diastolic BP with treatment duration but not with corresponding baseline BP values. In conclusion, Orlistat use contributes weight loss associated decrease in BP in overweight and obese subjects.

Topics: Anti-Obesity Agents; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Obesity; Orlistat; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss

Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy.. In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes.. Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

Topics: Anti-Obesity Agents; Benzazepines; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Compounding; Humans; Lactones; Liraglutide; Obesity; Orlistat; Phentermine; Weight Loss

Pediatric obesity is a serious public health concern. Five medications have been approved by the Food and Drug Administration (FDA) for chronic weight management in adults with obesity, when used as an adjunct to lifestyle modification. Orlistat is the only FDA-approved medication for pediatric patients aged 12 years and above.. This paper summarizes safety and efficacy data from clinical trials of weight loss medications conducted among pediatric samples. Relevant studies were identified through searches in PubMed.. Orlistat, as an adjunct to lifestyle modification, results in modest weight losses and may be beneficial for some pediatric patients with obesity. However, gastrointestinal side effects are common and may limit use. In adults taking orlistat, rare but severe adverse events, including liver and renal events, have been reported. Recent pediatric pharmacokinetic studies of liraglutide have demonstrated similar safety and tolerability profiles as found in adults, with gastrointestinal disorders being the most common adverse events. Clinical trials are needed of liraglutide, as well as other medications for obesity, that systematically evaluate their risks and benefits in pediatric patients.

Topics: Adult; Age Factors; Anti-Obesity Agents; Child; Combined Modality Therapy; Drug Approval; Humans; Lactones; Life Style; Liraglutide; Orlistat; Pediatric Obesity; Weight Loss

Obesity is an independent risk factor for the development of heart failure, and the two commonly co-exist. The European Society of Cardiology does not provide guidance regarding weight loss strategies in heart failure. The aim of this study was to systematically review the evidence for outcomes following intentional weight loss in patients with heart failure and obesity.. A systematic review of English articles was undertaken using databases PubMed, Embase and CENTRAL. Randomized controlled trials and observational studies reporting outcomes following intentional weight loss by lifestyle, surgical or pharmacotherapy intervention in patients with obesity and heart failure were included.. Four randomized controlled trials and seven observational studies were identified. Two randomized controlled trials used diet and exercise as an intervention, one used diet alone and one used a pharmacological intervention (orlistat). All but one reported significant weight loss. Two reported improvement in exercise capacity and quality of life. One reported improvement in New York Heart Association functional class in heart failure with preserved ejection fraction. The observational studies, five of which reported on outcomes following bariatric surgery, despite being small, heterogeneous and high risk of bias, suggested a trend in improvement of left ventricular function, quality of life and exercise capacity following weight loss.. Weight loss is achievable with lifestyle intervention in those with heart failure and obesity and may result in improvements in New York Heart Association classification, quality of life and exercise capacity.

Topics: Anti-Obesity Agents; Body Mass Index; Diet, Reducing; Exercise; Heart Failure; Humans; Obesity; Orlistat; Quality of Life; Weight Loss

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. Obesity is frequently present in these patients and plays a key role in the pathogenesis of both the endocrine and metabolic abnormalities of the syndrome, particularly infertility, hyperandrogenism and insulin resistance (IR). Diet and exercise is the mainstay of management of obesity in patients with PCOS. In contrast, the eff ects of antiobesity agents on weight and on the obesityrelated characteristics of the syndrome remain unclear. The aim of the present review is to summarize the current data on the eff ects of antiobesity drugs approved in Europe (orlistat, liraglutide 3 mg od and naltrexone/bupropion) on weight loss in patients with PCOS and to discuss their impact on the endocrine, reproductive and metabolic abnormalities of this population. Several studies reported that orlistat induces weight loss, improves IR and reduces androgen levels in PCOS. In contrast, data regarding the eff ects of the dose of liraglutide that is approved for the treatment of obesity (3 mg od) are very limited. Liraglutide 1.2-1.8 mg od results in weight loss in these patients but does not aff ect IR or androgen levels. Finally, there are no studies that evaluated naltrexone/bupropion in patients with PCOS and early studies reported conflicting results regarding the eff ects of naltrexone monotherapy on weight, IR and androgen levels. In conclusion, orlistat appears to have a role in the management of overweight and obese patients with PCOS whereas more studies are needed to clarify the role of liraglutide and naltrexone/bupropion.

Topics: Androgens; Anti-Obesity Agents; Bupropion; Drug Combinations; Female; Humans; Insulin Resistance; Liraglutide; Naltrexone; Obesity; Orlistat; Polycystic Ovary Syndrome; Weight Loss

Energy restriction and adherence required for weight loss without surgery Non-surgical weight loss treatment has not been shown to reduce mortality or cardiovascular morbidity, but can prevent diabetes mellitus and improves cardiovascular risk factors. For weight loss, energy restriction is fundamental and can lead to an average 2 to 20 kg loss over 6 to 12 months. Pharmacological treatment, behaviour therapy, physical activity and weight loss advice through web sites and smartphone applications and combinations in addition to energy restriction can contribute to further, but relatively limited weight loss up to 30 months. Adherence to the treatment is necessary for both weight loss and long-term weight loss maintenance.

Topics: Adult; Aged; Anti-Obesity Agents; Behavior Therapy; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise Therapy; Humans; Lactones; Middle Aged; Obesity; Orlistat; Patient Compliance; Risk Factors; Therapy, Computer-Assisted; Weight Loss

Orlistat, an inhibitor of intestinal lipase, promotes body weight reduction. The lipid-lowering efficacy of orlistat is controversial and the effect of orlistat-induced body weight reduction on lipid changes has not been explored in meta-regression analyses. A systematic literature search was conducted to identify randomized controlled trials investigating the efficacy of orlistat on plasma total, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides and lipoprotein(a) levels. Thirty-three studies were included in the meta-analysis (5522 and 4210 participants in the orlistat therapy and control groups, respectively). Orlistat reduced body weight (weighted mean difference: -2.12, p <0.001), total-cholesterol (weighted mean difference: -0.30mmol/L, p <0.001), low-density lipoprotein cholesterol (weighted mean difference: -0.27mmol/L, p <0.001), high-density lipoprotein cholesterol (weighted mean difference: -0.034mmol/L, p <0.001) and triglyceride (weighted mean difference: -0.09mmol/L, p <0.001) concentrations, while no effect on lipoprotein(a) was observed. Total- and low-density lipoprotein cholesterol-lowering were associated negatively with duration of orlistat treatment and positively with body weight changes. In conclusion, Orlistat treatment slightly reduces cholesterol and triglyceride levels, but not lipoprotein(a) levels. Total- and low-density lipoprotein cholesterol levels reductions are more consistent in patients with greater body weight reduction and shorter duration of orlistat treatment.

Topics: Anti-Obesity Agents; Body Weight; Cholesterol; Humans; Lactones; Lipids; Lipoproteins; Obesity; Orlistat; Randomized Controlled Trials as Topic; Triglycerides; Weight Loss

Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood.. To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force.. MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016.. English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings.. Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin.. Weight or excess weight (eg, body mass index [BMI]; BMI z score, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms.. There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: -0.86 (95% CI, -1.44 to -0.29; 6 studies; I2 = 0%) for metformin and -0.50 to -0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: -6.4 mm Hg (95% CI, -8.6 to -4.2; 6 studies; I2 = 51%) for systolic blood pressure and -4.0 mm Hg (95% CI, -5.6 to -2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%.. Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Topics: Adolescent; Advisory Committees; Anti-Obesity Agents; Body Mass Index; Body Weight; Child; Child, Preschool; Humans; Hypoglycemic Agents; Lactones; Mass Screening; Metformin; Non-Randomized Controlled Trials as Topic; Orlistat; Overweight; Pediatric Obesity; Randomized Controlled Trials as Topic; United States; Weight Loss

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

Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed.

Topics: Anti-Obesity Agents; Binge-Eating Disorder; Bulimia Nervosa; Cognitive Behavioral Therapy; Fructose; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.. To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.. MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.. Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.. Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.. Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.. Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.. Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.

Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

Topics: Adipokines; Bariatric Surgery; Combined Modality Therapy; Comorbidity; Diet, Reducing; Exercise Therapy; Female; Glucagon-Like Peptide 1; Gonadal Steroid Hormones; Humans; Hyperandrogenism; Inflammation; Insulin Resistance; Lactones; Life Style; Metformin; Models, Biological; Motivation; Obesity; Obesity, Abdominal; Orlistat; Polycystic Ovary Syndrome; Prevalence; Sympathetic Nervous System; Weight Loss

Orlistat is an effective adjunctive treatment to lifestyle modifications in the treatment of obesity. While the majority of current evidence is on the effect of orlistat in obese patients without diabetes, some studies suggest that patients who are obese and have diabetes mellitus lose more weight and have greater improvements in diabetic outcomes when treated with orlistat plus a lifestyle intervention than when treated by lifestyle interventions alone. The aim of this study was to review the evidence of the effects of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes. A systematic review of randomized controlled trials of orlistat in people with type 2 diabetes reporting diabetes outcomes in studies published between January 1990 and September 2013 was conducted. We searched for articles published in English in MEDLINE and EMBASE. Inclusion criteria included all randomized controlled trials of orlistat carried out on adult participants with a body mass index of 25 kg m(-2) or over diagnosed with type 2 diabetes, which reported weight change and at least one diabetic outcome. A total of 765 articles were identified out of which 12 fulfilled the inclusion criteria. The overall mean weight reduction (3, 6 and 12 months) in the orlistat group was -4.25 kg (95% CI: -4.5 to -3.9 kg). The mean weight difference between treatment and control groups was -2.10 kg (95% CI: -2.3 to -1.8 kg, P < 0.001), the mean HbA1c difference was -6.12 mmol mol(-1) (95% CI: -10.3 to -1.9 mmol mol(-1) , P < 0.004) and the mean fasting blood glucose difference was -1.16 mmol L(-1) (95% CI: -1.4 to -0.8 mmol L(-1) , P < 0.001). Treatment with orlistat plus lifestyle intervention resulted in significantly greater weight loss and improved glycaemic control in overweight and obese patients with type 2 diabetes compared with lifestyle intervention alone.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Diet, Reducing; Glycated Hemoglobin; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Treatment Outcome; Weight Loss

Obesity drugs have had a chequered history. In the recent past, only the low efficacy, pancreatic lipase inhibitor orlistat was available worldwide and it was little used. The 5HT2C agonist, lorcaserin, and two combinations of old drugs have been approved in the United States but not in Europe. The diabetes drug liraglutide has been approved in both the US and Europe and seems likely to be most widely accepted. In view of regulators' caution in approving obesity drugs, some (like beloranib) may initially be progressed for niche obesity markets. New drug targets have been identified in brown adipose tissue with the aim of not only activating thermogenesis but also increasing the capacity for thermogenesis in this tissue. Attempts are being made to match the efficacy of bariatric surgery by mimicking multiple gut hormones. Unapproved pharmacotherapies are tempting for some patients. Others remain optimistic about more conventional routes to pharmacotherapy.

Topics: Adipose Tissue, Brown; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Cinnamates; Clinical Trials as Topic; Cyclohexanes; Drug Approval; Drug Combinations; Epoxy Compounds; Europe; Humans; Lactones; Liraglutide; Molecular Targeted Therapy; Obesity; Orlistat; Sesquiterpenes; Thermogenesis; United States; Weight Loss

To use meta-analytic techniques to quantitatively evaluate the efficacy of orlistat and lorcaserin in the treatment of people who are overweight and obese.. We identified publications from searches of electronic databases and extracted data from studies that compared orlistat or lorcaserin to lifestyle advice (standard care), placebo, sibutramine, rimonabant or metformin and collected information on waist circumference change or withdrawals due to adverse events (AEs). A mixed treatment comparison (MTC) meta-analysis was performed on the data extracted.. Orlistat was found to be significantly better than placebo and standard care in reducing waist circumference at 6 and 12 months; orlistat reduced waist circumference by -6.96 cm [95% credible interval (CrI): -8.93, -4.96 cm] compared to standard care at 6 months. The results suggested that lorcaserin reduced waist circumference by a greater amount than all other interventions at 12 months, for example, lorcaserin lead to a greater reduction of -2.45 cm (95% CrI: -4.99, 0.08 cm) in comparison to placebo, although these differences were not statistically significant. Although data were very limited, metformin reduced waist circumference by a greater amount (-2.11 cm, 95% CI: -1.00, -3.22 cm) than orlistat at 6 months. On average, 6.5% of patients on orlistat and 5.4% of those on lorcaserin discontinued their treatment due to AEs at 12 months.. Orlistat should be considered as an addition to lifestyle interventions in the treatment of obesity. Lorcaserin has recently been approved by the US Food and Drug Administration (FDA) and these results suggest that it is similar in both efficacy and safety compared to orlistat.

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Lactones; Male; Metformin; Obesity; Orlistat; Risk Reduction Behavior; Treatment Outcome; Waist Circumference; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term, which encompasses simple steatosis and non-alcoholic steatohepatitis (NASH). The entire spectrum of NAFLD has been associated with metabolic syndrome. NASH is associated with increased mortality compared with that of the general population. Many therapeutic options for NASH have been studied. However, there is very little evidence supporting the efficacy of most regimens for the treatment of NASH.. To provide a review focusing on the current therapeutic options available for patients with NASH as well as to briefly introduce possible future interventions.. A MEDLINE, Pubmed and Cochrane Review database search using a combination of keywords, which included non-alcoholic fatty liver disease, non-alcoholic hepatic steatosis, NAFLD, NASH, treatment, therapeutics, vitamin E, orlistat and bariatric surgery. An overall summary of the articles was developed for each section of discussion in this review.. NASH associated with metabolic syndrome can progress advanced fibrosis and cirrhosis. Weight loss and lifestyle modification have been shown to improve NASH. Other medications used for weight loss and metabolic syndrome have been evaluated, such as orlistat, metformin and thiazolidinediones. Alternative regimens using ursodeoxycholic acid, statins and probiotics as well as bariatric surgery have been evaluated, but have not been recommended as first-line treatment for NASH. Vitamin E for NASH patients without diabetes seems to be promising. The lack of effective treatment for NASH suggests the heterogeneity of patients presenting with the NASH phenotype. The best treatment strategy for these patients may be to identify their pathogenic target and develop personalised treatment protocols.. Currently, there are few options available for the management of NASH. Future targeted treatment strategies based on the pathogenic pathways may be needed to develop effective treatment for patients with NASH.

Topics: Bariatric Surgery; Fatty Liver; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Metabolic Syndrome; Metformin; Non-alcoholic Fatty Liver Disease; Orlistat; Precision Medicine; Thiazolidinediones; Ursodeoxycholic Acid; Vitamin E; Weight Loss

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

Topics: Anti-Obesity Agents; Bariatric Surgery; Benzazepines; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Feeding Behavior; Female; Fructose; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Homeostasis; Humans; Islet Amyloid Polypeptide; Lactones; Male; Minimally Invasive Surgical Procedures; Obesity, Morbid; Orlistat; Phentermine; Receptors, Glucagon; Topiramate; Treatment Outcome; Weight Loss

Obesity is a global epidemic with important healthcare and financial implications. Most current antiobesity pharmacological therapies are unsatisfactory due to undesirable side effects. Many drugs have been withdrawn due to safety concerns. Maintaining weight loss remains the Achilles' heel of antiobesity therapy.. This is an overview of the use of liraglutide for obesity treatment. Clinical efficacy on weight, cardiovascular parameters, as well as safety and tolerability issues are discussed.. Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, which has a protracted pharmacokinetic profile compared to native GLP-1 while maintaining its biological activity. It induces weight loss by reducing appetite and energy intake. It stimulates insulin release and decreases glucagon secretion in response to hyperglycaemia. Treatment with liraglutide, in addition with diet and exercise, induces sustained mean weight loss of 7.6 kg at 2 years (weight loss induced by orlistat = 5.7 kg, phentermine/topiramate controlled release 15/92 = 10.9 kg). It reduces blood pressure and improves glycaemic control, which has clinically relevant significance on reducing obesity-related morbidity and mortality. Liraglutide is reasonably well tolerated with gastrointestinal side effects being most commonly encountered. Novo Nordisk filed for regulatory approval of liraglutide 3.0 mg for obesity treatment in December 2013.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hyperglycemia; Hypoglycemic Agents; Lactones; Liraglutide; Obesity; Orlistat; Receptors, Glucagon; Treatment Outcome; Weight Loss

Bariatric surgery has been safe and effective for treatment of severe obesity and comorbidities like type 2 diabetes mellitus (T2D). Nonetheless, weight loss and health outcomes vary considerably across individuals. Although the factors associated with outcomes are not fully understood, postoperative weight loss following any type of bariatric surgery is largely dependent on the extent to which patients can make and sustain changes in eating and activity. Therefore, lifestyle management including diet, exercise, and behavior modification is critical to helping patients achieve long-term weight loss. Pharmacotherapy and reoperation may also play a role after bariatric surgery. In this article, we highlight recent research findings in all of these areas to provide suggestions for how to enhance outcomes following bariatric surgery. Research on the mechanisms for weight loss and improvements in T2D following the different surgical procedures is needed to support the development of more personalized approaches to the multidisciplinary management of severe obesity.

Topics: Appetite Depressants; Bariatric Surgery; Behavior Therapy; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Directive Counseling; Exercise; Feeding Behavior; Gastric Bypass; Humans; Lactones; Obesity, Morbid; Orlistat; Patient Compliance; Phentermine; Pilot Projects; Postoperative Period; Randomized Controlled Trials as Topic; Weight Loss

Medications for the treatment of obesity began to appear in the late 19th and early 20th century. Amphetamine-addiction led to the search for similar drugs without addictive properties. Four sympathomimetic drugs currently approved in the US arose from this search, but may not be approved elsewhere. When noradrenergic drugs were combined with serotonergic drugs, additional weight loss was induced. At present there are three drugs (orlistat, phentermine/topiramate and lorcaserin) approved for long-term use and four sympathomimetic drugs approved by the US FDA for short-term treatment of obesity. Leptin produced in fat cells and glucagon-like peptide-1, a gastrointestinal hormone, provide a new molecular basis for treatment of obesity. New classes of agents acting on the melanocortin system in the brain or mimicking GLP-1 have been tried with variable success. Combination therapy can substantially increase weight loss; a promising approach for the future.

Topics: Anti-Obesity Agents; Benzazepines; Drug Therapy, Combination; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate; 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 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

The efficacy and safety of glucagon-like peptide (GLP)-1 receptor agonists for weight loss in adult patients without diabetes is reviewed.. GLP-1 receptor agonists have been associated with significant weight loss in patients with diabetes, raising the question of whether these agents could be used for weight loss in patients without diabetes. The mechanism by which GLP-1 receptor agonists induce weight loss is believed to be related to multiple actions involving the brain and gastrointestinal tract, with the primary action related to an increase in satiety. Trials examining the effects of GLP-1 receptor agonists for weight loss have compared exenatide, liraglutide, and orlistat. Of the studies completed to date, the majority of patients have been enrolled in trials involving liraglutide. Based on the reviewed literature, both exenatide 10 μg twice daily and liraglutide in dosages of up to 3 mg daily resulted in significant weight loss in patients without diabetes. A decrease in the proportion of patients with prediabetes was also found in studies of liraglutide. Nausea and vomiting were the most frequently reported adverse events in patients from these studies. Symptomatic hypoglycemia was reported in only one study with liraglutide in patients without diabetes and was not objectively confirmed by laboratory data. A higher frequency of psychiatric disorders, specifically insomnia, was reported by patients taking high doses of liraglutide.. GLP-1 receptor agonists offer a reasonable alternative for nondiabetic patients not able to achieve weight-loss goals with lifestyle modifications alone.

Topics: Adult; Dose-Response Relationship, Drug; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lactones; Life Style; Liraglutide; Obesity; Orlistat; Peptides; Receptors, Glucagon; Treatment Outcome; Venoms; Weight Loss

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

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Combinations; Fructose; Glucagon-Like Peptide 1; Humans; Lactones; Life Style; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; Weight Loss

Diagnosis is based on body mass index and waist circumference. The aim of treatment is to prevent and alleviate obesity comorbidities (e.g. type 2 diabetes, cardiovascular diseases, sleep apnoea and osteoarthritis) through a permanent weight reduction of at least 5%. The core element in management is lifestyle counselling on eating and exercise behaviours. This should be organised in primary care. Modalities supporting lifestyle changes include very-low-energy diets and orlistat drug therapy. Obesity surgery is indicated in cases of morbid obesity, if the appropriate conservative therapies do not lead to substantial weight loss. A flowchart presenting treatment options at different levels of health care is introduced.

Topics: Adult; Anti-Obesity Agents; Bariatric Surgery; Body Mass Index; Counseling; Diet; Exercise; Humans; Lactones; Life Style; Obesity; Orlistat; Waist Circumference; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is becoming a wide spread liver disease. The present recommendations for treatment are not evidence-based. Some of them are various weight reduction measures with diet, exercise, drug, or surgical therapy.. To assess the benefits and harms of intended weight reduction for patients with NAFLD.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, Science Citation Index Expanded, Chinese Biomedicine Database, and ClinicalTrials.gov until February 2011.. We included randomised clinical trials evaluating weight reduction with different measures versus no intervention or placebo in NAFLD patients.. We extracted data independently. We calculated the odds ratio (OR) for dichotomous data and calculated the mean difference (MD) for continuous data, both with 95% confidence intervals (CI).. The review includes seven trials; five on aspects of lifestyle changes (eg, diet, physical exercise) and two on treatment with a weight reduction drug 'orlistat'. In total, 373 participants were enrolled, and the duration of the trials ranged from 1 month to 1 year. Only one trial on lifestyle programme was judged to be of low risk of bias. We could not perform meta-analyses for the main outcomes as they were either not reported or there were insufficient number of trials for each outcome to be meta-analysed. We could meta-analyse the available data for body weight and body mass index only. Adverse events were poorly reported.. The sparse data and high risk of bias preclude us from drawing any definite conclusion on lifestyle programme or orlistat for treatment of NAFLD. Further randomised clinical trials with low risk of bias are needed to test the beneficial and harmful effects of weight reduction for NAFLD patients. The long-term prognosis of development of fibrosis, mortality, and quality of life should be studied.

Topics: Anti-Obesity Agents; Body Mass Index; Diet, Reducing; Exercise; Fatty Liver; Humans; Lactones; Life Style; Non-alcoholic Fatty Liver Disease; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

The extent to which community pharmacies can increase capacity for weight management is unknown. Thus, the objective of the present paper was to evaluate the effectiveness and cost-effectiveness of community pharmacy weight management interventions. This paper used a design of systematic review and narrative synthesis. Electronic databases (1999-2009) were searched, including Medline, EMBASE, CINAHL and Pharm-line. Weight management studies in community pharmacies were eligible for the inclusion criteria. All languages and study designs were considered. Outcome measures included body weight or anthropometry (at baseline and at least one follow-up time point). Data were extracted through independent, duplicate data extraction and quality assessment. As a result, 10 studies were included, totalling 2,583 service users and 582 pharmacies from the USA, the UK, Switzerland, Spain and Denmark. One was a randomized controlled trial of a meal-replacement versus a reduced calorie diet. A non-randomized controlled before and after study compared community pharmacist treatment using Orlistat with usual care. Eight studies were uncontrolled. Five studies described behaviour change techniques. Long-term (12 months) mean weight loss measured in three studies ranged from 1.1 to 4.1 kg. Four uncontrolled studies reported statistically significant weight loss. No study reported economic evaluations. Currently, there is insufficient evidence for the effectiveness and cost-effectiveness of community pharmacy-based weight management initiatives to support investment in their provision.

Topics: Anti-Obesity Agents; Community Pharmacy Services; Cost-Benefit Analysis; Female; Humans; Lactones; Male; Obesity; Orlistat; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss

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

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

Obesity has adverse consequences in the general population. In patients with chronic kidney disease (CKD), it is associated with increased inflammation, insulin resistance, hypertension and dyslipidaemia, which are important risk factors for CKD progression and death. In adults with CKD stages 1-4, weight loss should be encouraged, it reduces proteinuria and glomerular hyperfiltration, which are frequent in obese patients. Proposals for modifications of lifestyle, physical activity and calorie restriction are the first measures. Pharmacological treatments are generally unsafe in these patients, except orlistat, but that has modest efficacy. Bariatric surgery may be the only option in severe obesity, if all other measures fail. For obese patients on dialysis treatment, who are eligible for kidney transplantation, weight loss is mandatory to prevent obesity-related surgical complications and improve patient and graft survival after transplantation. Interventions should place an emphasis on exercise to increase muscle mass, and calorie but not protein restriction. Bariatric surgery should be carried out by experienced surgeons due to the high risk of complications. For obese patients who are not considered transplant candidates the benefits of weight loss remain uncertain.

Topics: Anti-Obesity Agents; Bariatric Surgery; Combined Modality Therapy; Diet, Reducing; Exercise; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Transplantation; Lactones; Obesity; Orlistat; Postoperative Complications; Renal Dialysis; Risk Factors; Weight Loss

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

Both obesity and type 2 diabetes are associated with increased morbidity and mortality. Published data suggest that orlistat 120 mg, a lipase inhibitor used to treat obesity, may improve glycaemic parameters through weight loss-independent effects.. To investigate the effect of orlistat 120 mg on weight loss, and assess whether changes in glycaemic parameters [fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)] are independent of weight loss.. This retrospective analysis of pooled data from seven multicentre, double-blind, placebo-controlled studies involved overweight or obese patients with type 2 diabetes (aged 18-70 years). Patients were required to have a body mass index of 27-43 kg/m2, HbA1c of 6.5 to <13%, and stable weight for > or =3 months. Subjects received orlistat 120 mg tid or placebo for 6 or 12 months.. A total of 2550 overweight or obese patients with type 2 diabetes were enrolled and randomized to treatment with orlistat 120 mg tid (n = 1279) or placebo (n = 1271). For the whole population, patients treated with orlistat 120 mg had significantly greater mean decreases in FPG compared with placebo-treated patients (-1.39 mmol/l vs. -0.47 mmol/l; p < 0.0001). In addition, orlistat 120 mg provided significantly larger mean decreases in HbA1c compared with placebo (-0.74% vs. -0.31%; p < 0.0001). For patients with minimal weight loss (< or =1% of baseline body weight), orlistat 120 mg still provided a significantly greater decrease in the least squares mean value for both FPG (-0.83 mmol/l vs. +/-0.02 mmol/l; p = 0.0052) and HbA1c -0.29% vs. +/-0.14%; p = 0.0008). This suggested that the improvement of glycaemic control with orlistat 120 mg was independent of weight loss. Using linear regression analysis, improvement in glycaemic control (FPG and HbA1c) with orlistat 120 mg was less strongly correlated with weight loss than for placebo.. Orlistat 120 mg appears to improve glycaemic control more than would be predicted by weight loss alone in overweight or obese patients with type 2 diabetes. Postulated mechanisms underlying this effect include an improvement of insulin sensitivity, a slower and incomplete digestion of dietary fat, reduction of postprandial plasma non-esterified fatty acids, decreased visceral adipose tissue, and stimulation of glucagon-like peptide-1 secretion in the lower small intestine.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss; Young Adult

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

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

As two-thirds of the US population is overweight or obese, new strategies are needed to help individuals safely and effectively lose weight. One option is to use dietary supplements, but not all supplements that are touted for weight loss have published clinical support for efficacy. The purpose of this article was to identify all published articles on dietary supplements for weight loss. Effectiveness of these supplements was defined as promoting 1-2 lb of weight loss each week. Although several dozen different dietary supplements are sold, only 14 published studies were identified. Four individual ingredients and three blends of ingredients were considered to be effective. Additionally, we compared weight loss from these dietary supplements to over-the-counter (OTC) orlistat (alli™, GlaxoSmithKline, Brentford, UK). Five single ingredients and three blends of ingredients produced more weight loss than OTC orlistat. Persons who use dietary supplements for weight management, counsel patients on how to lose weight, and retailers who sell dietary supplements, should become familiar with those supplements only that are effective at producing weight loss to assure the best results.

Topics: Citrates; Dietary Supplements; Humans; Lactones; Micronutrients; Obesity; Orlistat; Phytotherapy; Picolinic Acids; Plant Extracts; Weight Loss

There has been an increase in the concern about preventing type 2 diabetes mellitus (T2DM), a disease with great and increasing prevalence. The prevalence of obesity, physical inactivity, Western processed diet, important risk factors for the development of T2DM, are also rising. Free fatty acids are increased in obesity and reduce insulin clearance and increase hepatic glucose production. Implementation of a healthy lifestyle has been show to slow the progression of impaired glucose tolerance to T2DM. Orlistat is an inhibitor of lipase activity, with proved efficacy in body weight reduction and long-term management of obesity and more favorable effects on carbohydrate metabolism and it was prospectively shown in XENDOS study that orlistat promoted long-term weight loss and prevented T2DM onset in obese individuals with normal and impaired glucose tolerance at baseline over four years. This benefit could be associated to the weight loss itself, to the limited absorption of lipids and reduction of plasma free fatty acids, to increased production of incretins or to modulation of secretion of cytokines by adipocytes, all effects secondary to orlistat treatment. A proposed strategy is to identify subjects at highest risk to receive a drug intervention, using lifestyle interventions alone at the community level.

Topics: Anti-Obesity Agents; Diabetes Mellitus, Type 2; Diet; Exercise; Humans; Lactones; Life Style; Obesity; Orlistat; Risk Factors; Treatment Outcome; Weight Loss

Overnutrition resulting in obesity plays a key role in nonalcoholic fatty liver disease, the major reason for abnormal liver function in many parts of the world. Currently, it is not clear which type of diet preferentially results in this common disease.. Excess nutrition leads to accumulation of various lipids in the liver, where fatty acids are considered the main driving force in the disease process. A liver loaded with fat is commonly associated with insulin resistance, the key pathophysiological phenomenon observed in nonalcoholic fatty liver disease. Not surprisingly, attempts to reduce body weight and thereby total liver fat are considered the key therapeutical steps in this disorder. Although voluntary weight loss is often not successful to reverse the disease process, various surgical procedures have proven effective in reducing overweight situations and liver steatosis. Weight loss not only reduces the amount of liver fat but also might improve inflammation and fibrosis in nonalcoholic steatohepatitis.. Although pharmacological approaches are eagerly awaited to achieve similar benefits; current available therapies have so far not fulfilled this expectation. Despite this frustration, such approaches are expected to be available in the near future.

Topics: Animals; Anti-Obesity Agents; Cytokines; Diet; Exercise Therapy; Fatty Liver; Humans; Lactones; Lipids; Obesity; Orlistat; Oxidative Stress; Weight Loss

The prevalence of obesity and the metabolic syndrome (MS) is on the rise, and subsequently the hepatic manifestation of MS, nonalcoholic fatty liver disease (NAFLD), has become a common entity in clinical practice. Most patients with NAFLD face medical complications related to their underlying MS in other organ systems; however, a small but significant group of patients with the more aggressive form of fatty liver, nonalcoholic steatohepatitis (NASH), are at risk of developing cirrhosis and hepatocellular carcinoma. As patients are generally asymptomatic, often their disease goes unrecognized. This is particularly true for NASH, where liver biopsy is currently required to make the diagnosis. Once diagnosed, no one treatment has been shown to be universally efficacious and those that are of benefit are not without side effects. Effective treatment regimens directed at both decreasing insulin resistance as well as the processes leading to necroinflammation and hepatic fibrosis have been investigated and include lifestyle modification, surgical therapies, and pharmacotherapy. This review focuses on current and potential future therapies for NASH.

Topics: Animals; Antioxidants; Bariatric Surgery; Body Mass Index; Cannabinoids; Cholagogues and Choleretics; Comorbidity; Fatty Liver; Glucagon-Like Peptide 1; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Insulin Resistance; Lactones; Life Style; Metformin; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Thiazolidinediones; Treatment Outcome; Ursodeoxycholic Acid; Weight Loss

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

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

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

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

According to the Centers for Disease Control and Prevention, the prevalence of obesity among adolescents ages 12 to 19 has soared in recent decades, from 5% in 1980 to 16% in 2002. Recent neuroendocrinologic research may help to explain the complexity of obesity and help providers develop more effective weight-loss strategies. Combining medical intervention with an individualized cognitive-behavioral program is the best approach for adolescents. Accompanying sidebars examine several such programs and provide additional resources for clinicians.

Topics: Adolescent; Adult; Anti-Obesity Agents; Behavior Therapy; Child; Emotions; Feeding Behavior; Female; Humans; Lactones; Male; Neurosecretory Systems; Obesity, Morbid; Orlistat; Weight Loss

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

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

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

Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults - at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003). Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.

Topics: Anti-Obesity Agents; Comorbidity; Drug Interactions; Humans; Lactones; Obesity; Orlistat; Patient Compliance; Weight Loss

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

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

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

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

Orlistat (Xenical) is a reversible inhibitor of gastric and pancreatic lipases. In conjunction with a hypocaloric diet and moderate exercise, orlistat is an effective drug for use in the management of obesity in adults with or without comorbidities. Recent data have shown that orlistat is also effective as a component of weight management strategies in obese adolescents. In addition to its well established efficacy in achieving modest weight loss, orlistat has been shown to improve glycaemic parameters in obese adults with type 2 diabetes mellitus as well as some features of the metabolic syndrome. Orlistat is generally well tolerated. Thus, orlistat is an option for the treatment of obese patients with or without type 2 diabetes and also has a role in the management of obese patients with the metabolic syndrome, associated comorbidities or concomitant disorders.

Topics: Adolescent; Adult; Anti-Obesity Agents; Biological Availability; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Lactones; Male; Obesity; Orlistat; Overweight; Randomized Controlled Trials as Topic; 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

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

The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes.. Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results.. A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of euro14 000 in Sweden and euro13 600 in Switzerland.. The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.

Topics: Anti-Obesity Agents; Blood Pressure; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insurance, Health, Reimbursement; Lactones; Obesity; Orlistat; Sweden; Switzerland; Treatment Outcome; Weight Loss

Orlistat is an antiobesity drug with a well documented efficacy in weight reduction and weight maintenance. Weight reduction with orlistat has been associated with a favourable effect on obesity-related cardiovascular risk factors. Orlistat treatment is associated with a reduction in serum insulin levels. Moreover, orlistat reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance and lowers the required dose of metformin, sulfonylureas and insulin in patients with type 2 diabetes. Furthermore, orlistat can reduce total and low density lipoprotein (LDL) cholesterol levels and improve postprandial triglyceridemia, as well as the low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio (LDL/HDL ratio). Moreover, orlistat appears to have a favourable effect on some inflammatory markers, such as TNF-alpha and interleukin-6 and has a time-depended effect on some haemostatic factors.

Topics: Anti-Obesity Agents; Apolipoproteins; Cardiovascular Diseases; Clinical Trials as Topic; Coronary Disease; Fatty Acids, Nonesterified; Humans; Lactones; Lipoproteins; Orlistat; Risk Factors; Triglycerides; Weight Loss

The prevalence of obesity in industrialized countries has reached epidemic proportions, with about one in three people being obese and another one in three people being overweight and at risk of developing obesity. In recent years, obesity has gained the traditional tetrad of cardiovascular risk factors of smoking: hypertension, dyslipidemia, and dysglycemia. Attention has also focused on the importance of abdominal (or central) obesity as a determinant of cardiovascular risk, independent of the body mass index. In addition to effects on coronary artery disease, obesity has an effect on cardiovascular disease, including stroke, ventricular function, peripheral arterial disease, and venous thromboembolism. The objectives of this review are to summarize the effects of obesity on cardiovascular disease, and the possible mechanisms for these associations, and to investigate the effects of weight-loss interventions on the burden of cardiovascular disease. Large ongoing clinical outcome trials, such as the SOS study, the Look-AHEAD trial, or the SCOUT study, should provide important information on the effects of surgical and nonsurgical obesity treatment on cardiovascular morbidity and mortality.

Topics: Adult; Age Distribution; Aged; Body Mass Index; Cardiovascular Diseases; Combined Modality Therapy; Comorbidity; Diet, Reducing; Exercise; Female; Humans; Lactones; Life Style; Male; Middle Aged; Obesity; Orlistat; Prevalence; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Analysis; Weight Loss

To calculate the cost effectiveness (from the Swedish healthcare perspective) of orlistat plus diet for an obese and overweight population in a 1-year weight-management responder programme versus a 1-year weight-management programme based on diet only. As a reference, orlistat plus diet and diet only were also compared with a no-diet alternative.. Costs and effectiveness were calculated in a decision-tree model by means of Monte Carlo simulation. Efficacy was derived from a pooled analysis of the orlistat clinical trial programme. Acquisition costs for orlistat (euro, 2003 prices), healthcare costs for visits to doctors and dieticians related to weight management, and costs related to the difference in diabetes mellitus incidence between treatment arms were included in the analysis. The health benefit of temporary weight loss was measured in the number of quality-adjusted life-years (QALYs) gained.. The number of responding (those with >5% weight loss) patients at month 3 was almost twice as high with orlistat compared with diet only: 48.9% versus 26.3%. Responding orlistat patients had a weight loss of 15.5% at month 12 compared with 7.9% for all patients on diet only. The incremental cost-effectiveness ratio (ICER) per QALY gained versus diet only was estimated to be 13,125 euro for the average patient starting on orlistat. When orlistat was compared with no diet, the cost effectiveness was improved. However, comparing diet only with no diet gave a slightly higher ICER, indicating that orlistat had an extended dominance over the diet-only alternative.. Our estimates indicated that orlistat in a 12-month dietary responder programme increased the number of QALYs and reduced the cumulative incidence of diabetes compared with diet only. Patients starting on orlistat in addition to a dietary programme achieved an ICER that was similar to many other well accepted healthcare treatment programmes. In order to improve the precision of our calculations, we need to confirm the key assumptions regarding temporary weight loss and utility gains, and the relationship between temporary weight loss and diabetes, as well as other co-morbidities, and to have better knowledge of the long-term impact of weight-management programmes in clinical practice, such as changes in weight-controlling behaviours and sustainability of weight loss.

Topics: Adult; Anti-Obesity Agents; Cost-Benefit Analysis; Decision Trees; Diet, Reducing; Female; Health Care Costs; Humans; Lactones; Male; Monte Carlo Method; Obesity; Orlistat; Overweight; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Sweden; Treatment Outcome; Weight Loss

Orlistat (tetrahydrolipstatin) is an inhibitor of gastrointestinal lipases, especially pancreatic lipase. It is used as an adjunct to diet and exercise in order to achieve weight loss in obese individuals (body mass index > 30 kg/m2) or in overweight individuals (body mass index > 27 kg/m2) with other risk factors for atherosclerotic vascular disease, such as hypertension, dyslipidaemia or diabetes. Short- and long-term studies of up to 4 years duration have shown the drug to have significant benefits in weight loss, as well as in the reduction in lipids, glucose and haemoglobin A1c, and in time to onset of Type 2 diabetes compared with diet alone or placebo groups. The incremental amount of weight loss that orlistat produces is modest, but sufficient to result in improvement in obesity comorbidities such as elevated blood pressure, dyslipidaemia and hyperglycaemia compared with diet and exercise alone. Orlistat should only be prescribed for individuals who are motivated to adhere to lifestyle modifications, especially dietary fat restriction.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Dyslipidemias; Enzyme Inhibitors; Exercise; Gastrointestinal Tract; Humans; Lactones; Lipase; Multicenter Studies as Topic; Obesity; Orlistat; Patient Compliance; Randomized Controlled Trials as Topic; Weight Loss

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

The aim of this paper is to assess the clinical effectiveness of orlistat used for the management of obesity. Nineteen electronic databases were searched for randomized controlled trials evaluating the effectiveness of orlistat for weight loss or maintenance of weight loss in overweight or obese patients. Each included trial was assessed for methodological quality. Statistical pooling was performed when trials were considered to be sufficiently similar. Twenty-three trials were eligible for inclusion. Placebo-controlled trials recruiting patients with uncomplicated obesity reported statistically significant differences in favour of orlistat for weight loss and changes in obesity-related risk factors at all time points. Trials in obese patients with defined risk factors at baseline showed similar results, however, smaller effect sizes were observed in patients with type 2 diabetes. The effectiveness of orlistat relative to other anti-obesity drugs is currently unclear. When orlistat was added to simvastatin, this proved to be more effective for weight loss than either drug used individually. Orlistat use is associated with a higher incidence of gastrointestinal adverse events compared with placebo. In conclusion, orlistat is more effective than placebo in promoting weight loss, maintenance of weight loss, and improving cardiovascular risk factor profiles. Baseline parameters of patients seen in clinical practice should be taken into account when considering treatment.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat; Placebos; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Weight Loss

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 growing health concern in Canada and the United States, and pharmacologic therapies such as orlistat are being more commonly prescribed to assist with weight loss.. Our goal was to assess the efficacy and safety of orlistat compared with either placebo or an active control with regard to weight loss and serum lipid changes in overweight patients.. We performed a systematic literature search of MEDLINE (1966 through December 2003) and the Cochrane Central Register of Controlled Trials. Relevant trials and reviews were searched by hand. Randomized trials comparing orlistat and a control and reporting changes in weight loss, serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol, LDL:HDL, and triacylglycerols), or both in overweight and obese patients [body mass index (in kg/m2) > or =25] were included.. Twenty-eight randomized trials met our inclusion criteria. Seventeen studies including 10,041 patients compared 3 x 120 mg orlistat/d with placebo or an inactive control along with a hypocaloric diet over a 1-y period. Relative risks (RRs) associated with clinically significant weight losses of 5% and 10% were 1.74 (95% CI: 1.57, 1.91) and 1.96 (1.74, 2.21), both favoring orlistat. Improvement in total cholesterol, LDL cholesterol, HDL cholesterol, and LDL:HDL were also greater with orlistat. Gastrointestinal events were more common with orlistat than with placebo [RR: 1.46 (1.37, 1.55)].. Our findings suggest that 3 x 120 mg orlistat/d is effective for improving both weight loss and serum lipid profiles in obese patients at low and high cardiovascular disease risk and in obese patients with type 2 diabetes.

Topics: Adult; Anti-Obesity Agents; Body Weight; Diet, Reducing; Energy Intake; Female; Humans; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Randomized Controlled Trials as Topic; Safety; Treatment Outcome; Weight Loss

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

Four prospective randomised long-term studies have been recently completed and published (Diabetes Prevention Study, Diabetes Prevention Program, STOP-NIDDM trial, XENDOS Study). Both of them clearly demonstrate the possibility to delay and/or prevent the onset of type 2 diabetes in at high-risk subjects with impaired glucose tolerance, through changes in lifestyle (dietary intervention, weight reduction, increased physical activity) or drug treatment (metformin, acarbose, orlistat). These studies are reviewed and practical implications of their results are discussed.

Topics: Acarbose; Adult; Aged; Diabetes Mellitus, Type 2; Diet; Exercise; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Lactones; Life Style; Male; Metformin; Middle Aged; Orlistat; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; 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

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, 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

To investigate the effects of long-term weight management with orlistat on blood pressure in obese hypertensive patients.. A meta-analysis of data from five multicenter, randomized, placebo-controlled studies, conducted in Europe and the USA, was performed.. Obese adults [body mass index (BMI) 28-43 kg/m(2) ] with uncontrolled diastolic hypertension or isolated systolic hypertension (ISH) were eligible for inclusion.. Following a 4-week placebo lead-in period, patients were randomized to orlistat 120 mg or placebo three times daily, in conjunction with a mildly reduced calorie diet for 1 year.. Change in body weight was the primary efficacy parameter. Blood pressure, heart rate and systolic workload were assessed as secondary efficacy parameters.. A total of 628 patients were included in the intent-to-treat (ITT) analysis. After 56 weeks, orlistat-treated patients had lost significantly more body weight than placebo recipients (8.0 versus 4.0%; P<0.001). Among patients with ISH, mean systolic pressure was reduced to a significantly greater degree after 1 year with orlistat compared to placebo (-9.4 versus -4.6 mmHg; P= 0.022). Similarly, reductions in mean diastolic pressure in patients with diastolic hypertension were greater with orlistat than with placebo (-7.7 versus -5.6 mmHg; P= 0.017). Weight loss of >or= 10% was associated with significant reductions in blood pressure, heart rate and systolic workload.. Orlistat promotes clinically meaningful weight loss that is associated with significant reductions in blood pressure and heart rate, and may therefore have a role in the management of hypertension in overweight and obese patients.

Topics: Anti-Obesity Agents; Blood Pressure; Humans; Hypertension; Lactones; Multicenter Studies as Topic; Obesity; Orlistat; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss

Topics: Adolescent; Adolescent Behavior; Anti-Obesity Agents; Body Mass Index; Diabetes Mellitus, Type 2; Exercise; Female; Gastric Bypass; Humans; Lactones; Obesity; Orlistat; Polycystic Ovary Syndrome; Weight Loss

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

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

The prevalence of Type 2 diabetes mellitus (DM-2) is increasing throughout the world and poses a major public health concern. With the majority of patients DM-2 are overweight or obese and weight loss is generally recommended, both as a first-line therapy and as an adjunct to pharmacological therapies. However, it is generally acknowledged that weight loss, a difficult goal for many overweight and obese individuals, is especially difficult for those with DM-2 and there is interest in whether pharmacological adjuncts may be useful for this purpose. Orlistat is an intestinal lipase inhibitor previously approved for the treatment of obesity. During the past several years, clinical trials have been completed concerning the use of orlistat in the treatment of overweight or obese patients with DM-2. The purpose of this review is to examine the results of these clinical trials. Data on > 2500 orlistat-treated patients with DM-2 are reviewed and summarised. Orlistat therapy led to greater weight loss and improved metabolic control in overweight and obese patients with DM-2.

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Obesity; Orlistat; Sulfonylurea Compounds; 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

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

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

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

More than half of the men and women in the United States are overweight or obese. Obesity is associated with an increased risk for various diseases, most notably, hypertension, diabetes mellitus, dyslipidemia, and coronary heart disease (CHD). The location of excessive body fat, particularly in the visceral area, has the strongest association with these factors that comprise the insulin resistance syndrome. A reduction in as little as 10% of baseline weight has been shown to improve the control of blood pressure and glucose, as well as to reduce triglycerides and increase high-density lipoprotein (HDL) cholesterol. Therefore, obesity should be considered a predisposing CHD risk factor, and treatment with diet, exercise, and newer pharmacologic agents can help patients achieve and maintain desired weight-loss goals.

Topics: Anti-Obesity Agents; Arteriosclerosis; Coronary Disease; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Risk Factors; Weight Loss

Orlistat is a novel, noncentrally acting antiobesity agent that selectively inhibits gastrointestinal lipase activity, thereby reducing the absorption of dietary fat by approximately one-third. In a series of 1- and 2-yr randomized, placebo-controlled trials of obese subjects, treatment with orlistat in combination with a mildly calorie-restricted diet consistently produced significantly greater mean weight loss than diet alone. More orlistat-treated subjects than placebo recipients achieved clinically meaningful weight reduction (> or =5% or > or =10% of initial body weight) after 1 and 2 yr. Orlistat was also associated with a significant reduction in the regain of lost weight during long-term treatment. In addition, orlistat therapy resulted in significant improvements in several cardiovascular risk factors including serum total and low-density lipoprotein-cholesterol, serum insulin levels, systolic and diastolic blood pressure, and waist circumference. Furthermore, obese subjects with type 2 diabetes achieved a significantly greater decrease in body weight with orlistat compared with placebo, as well as significant improvements in HbA1c and fasting glucose levels. Among subjects with impaired glucose tolerance, orlistat compared with placebo reduced the proportion who developed type 2 diabetes. Conversely, orlistat increased the proportion of subjects who achieved a normalization of glucose tolerance. Orlistat acts locally in the gastrointestinal tract and is only minimally absorbed. In long-term clinical trials, orlistat was well tolerated by both diabetic and nondiabetic subjects.

Topics: Anti-Obesity Agents; Body Weight; Cardiovascular Diseases; Dietary Fats; Energy Metabolism; Humans; Intestinal Absorption; Lactones; Obesity; Orlistat; Weight Loss

Obesity is an increasing health problem in most developed countries and its prevalence is also increasing in developing countries. There has been no great success with dietary means and life style modification for permanent weight loss. Various surgical treatment methods for obesity are now available. They are aimed at limiting oral energy intake with or without causing dumping or inducing selective maldigestion and malabsorption. Based on current literature, up to 75% of excess weight is lost by surgical treatment with concomitant disappearance of hyperlipidaemias, type 2 diabetes, hypertension or sleep apnoea. The main indication for operative treatment is morbid obesity (body mass index greater than 40 kg/m2) or severe obesity (body mass index > 35 kg/m2) with comorbidities of obesity. Orlistat is a new inhibitor of pancreatic lipase enzyme. At doses of 120 mg three times per day with meals it results in a 30% reduction in dietary fat absorption, which equals approximately 200 kcal daily energy deficit. In the long term, orlistat has been shown to be more effective than placebo in reducing body weight and serum total and low-density lipoprotein cholesterol levels. Orlistat has a lowering effect on serum cholesterol independent of weight loss. Along with weight loss, orlistat also favourably affects blood pressure and glucose and insulin levels in obese individuals and in obese type 2 diabetic patients.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Humans; Lactones; Lipase; Multicenter Studies as Topic; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Factors; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Behavior Therapy; Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Orlistat, a potent inhibitor of the pancreatic and intestinal lipases, is the first member of a new therapeutic class approved for the treatment of obesity. Its administration with fat-containing foods results in a partial inhibition of triglyceride hydrolysis in the digestive lumen and subsequent reduction of the free fatty acids and monoglycerides absorption. At the usual dosage of 120 mg tid, about 30% of ingested fat are excreted non digested in feces. When administered with a mildly hypocaloric diet, orlistat contributes to loss of weight by a additional caloric deficit and promotes further compliance of the obese patient to the dietary recommendations. Several double-blinded, placebo-controlled studies have shown a statistically significant loss of weight of about 10% when orlistat was prescribed with a well balanced, mildly hypocaloric diet to obese patients during one year. Moreover, small but significant beneficial changes in the serum lipid levels occurred in these patients. Because the orlistat molecule is not reabsorbed, its side effects are mostly due to the gastrointestinal effects and consist in steatorhea after fatty meals. However, the treatment is generally well tolerated. Since the recent withdrawal from the worldwide market of the anorectic agents, phentermine and fenfluramine, orlistat is at this time the only drug approved by the European Community for the treatment of obesity. However, its long-term value are not currently known.

Topics: Anti-Obesity Agents; Combined Modality Therapy; Diet, Reducing; Drug Approval; Europe; Humans; Lactones; Obesity; Orlistat; Treatment Outcome; Weight Loss

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 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

Prevention and treatment of obesity are major clinical problems encountered in the management of Type 2 diabetes mellitus (DM); indeed, up to 90% of such patients are regarded as being overweight. Except for a brief period following diagnosis, when presumably enthusiasm to adopt lifestyle change is at its greatest, weight gain is generally progressive unless severe hyperglycaemia or complications intervene. Even a relatively modest weight loss of 10% can have major benefits in terms not only of reducing the risk of developing DM in the first place, but also in improving metabolic control after the disorder has become established. Behavioural therapy (BT) in combination with hypocaloric diet achieves weight loss in the short-term, but is poorly sustained in the long-term. Exercise has metabolic benefits beyond its rather minimal effects on short-term weight loss in that it may also aid long-term weight control. The difficulties encountered in maintaining lifestyle change do, however, suggest the need for ongoing intervention--perhaps including a regular period on a stricter dietary regimen (800-1000 kcalday-1), possibly a very low calorie diet (VLCD)(< 800 kcalday-1) or even the use of orlistat, a pancreatic lipase inhibitor which reduces the absorption of dietary fat. Realistically, the aim should be for long-term weight stability.

Topics: Anti-Obesity Agents; Behavior Therapy; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Exercise; Humans; Lactones; Life Style; Obesity; Orlistat; Weight Gain; Weight Loss

Topics: Adult; Anti-Obesity Agents; Clinical Trials as Topic; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Prognosis; Treatment Outcome; Weight Loss

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

Topics: Acarbose; Anti-Obesity Agents; Appetite Depressants; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Humans; Hypoglycemic Agents; Lactones; Life Style; Metformin; Obesity; Orlistat; Weight Loss

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

Being overweight increases the risk of developing many common diseases including type-2 diabetes mellitus, hypertension, coronary heart disease, gallstones and various cancers of the gastrointestinal and urogenital tracts. It can also cause or exacerbate osteoarthritis, breathlessness, heartburn, sleep apnoea, venous thromboembolism and psychological distress, particularly anxiety and depression. It makes anaesthesia and surgery more hazardous, and in pregnancy increases the risks associated with childbirth. Being overweight can also complicate day-to-day social functioning such as negotiating seats on public transport or purchasing clothes. In this article, we review the evidence that weight loss is beneficial and how this might be achieved using lifestyle changes, drug therapy, or surgery.

Topics: Anti-Obesity Agents; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat; Weight Loss

Lipase inhibition, leading to decreased intestinal fat adsorption can be used in the treatment of obesity. Orlistat, a lipase inhibitor, in a dose of 50 mg three times a day leads to a significant increase in weight loss compared to placebo in moderately obese people. These results are confirmed in a multiple-dose study using 10 mg, 60 mg and 120 mg Orlistat three times a day vs. placebo. The use of lipase inhibition has no significant influence on fasting levels of several hormonal systems, including thyroid hormones, catecholamines and IGF-I. The same is true for the responses of several gastrointestinal and pancreatic hormones after a liquid high-fat mixed meal. In general, Orlistat is tolerated very well, although a higher occurrence of gastrointestinal side effects is seen.

Topics: Adult; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Orlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks.. A total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 1:1 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism.. The experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7β-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups.. Orlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis

Topics: Adult; Anti-Obesity Agents; Cholesterol; Double-Blind Method; Humans; Lactones; Lipase; Obesity; Orlistat; Overweight; Oxysterols; Phentermine; Weight Loss

Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile.. Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD).. Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT.. Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD.. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

Topics: Alanine Transaminase; Anti-Obesity Agents; Body Mass Index; Cannabinoid Receptor Antagonists; Case-Control Studies; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Liver Diseases; Metformin; Obesity; Orlistat; Pioglitazone; Piperidines; Polycystic Ovary Syndrome; Prognosis; Pyrazoles; Receptor, Cannabinoid, CB1; Retrospective Studies; Rimonabant; Thiazolidinediones; Weight Loss

Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications.. To explore whether the decreased body weight in these patients is associated with a worsened psychopathology.. In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test.. Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores.. Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Female; Humans; Lactones; Lipid Metabolism; Male; Middle Aged; Obesity; Olanzapine; Orlistat; Psychiatric Status Rating Scales; Psychopathology; Schizophrenia; Weight Loss

To evaluate the efficacy of an orlistat-resveratrol (O-R) combination in subjects with obesity over a 6-month period.. This study was a double-blind, parallel, randomized controlled clinical trial. Patients fulfilling the selection criteria (age from 20 to 60 years and body mass index (BMI) ≥30 and ≤39.9 kg/m(2) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks. Then the participants were randomly assigned to four groups, placebo, resveratrol, orlistat, or O-R, and they consumed the energy-reduced diet for 6 months. The study consisted of seven visits. During each visit, a 24-h recall was performed, along with measurements of anthropometric and serum biochemical parameters.. A total of 161 participants were selected. Of these, 84 participants completed the study. A significant weight loss of -6.82 kg (95% CI -8.37 to -5.26) was observed in the O-R group compared with -3.50 kg (-5.05 to -1.95, P = 0.021) in the placebo group. In contrast, the -6.02 kg (-7.68 to -4.36) orlistat and -4.68 kg (-6.64 to -2.71) resveratrol monotherapy losses did not significantly differ from the placebo. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination.. The O-R combination was the most effective weight loss treatment.

Topics: Adult; Aged; Anthropometry; Anti-Obesity Agents; Body Mass Index; Caloric Restriction; Diet; Double-Blind Method; Drug Therapy, Combination; Energy Intake; Female; Humans; Lactones; Leptin; Male; Mexico; Middle Aged; Obesity; Orlistat; Placebos; Resveratrol; Stilbenes; Treatment Outcome; Triglycerides; Weight Loss

We compared the effects of three weight loss interventions on serum concentrations of adiponectin and leptin in obese premenopausal women.. 114 obese Caucasian women were randomized into three groups receiving a low-calorie diet (LC; n = 39), an isocaloric diet with 500 mg of metformin twice a day (IM; n = 38), and an isocaloric diet with 120 mg of orlistat three times a day (IO; n = 37), for three months. Serum concentrations of adiponectin and leptin were evaluated, along with anthropometric and body composition parameters, at baseline and after the study.. Both IO and LC, but not IM, caused an increase in serum adiponectin concentration (p < 0.01, p < 0.05 respectively). A decrease in serum leptin level was documented in the LC (p < 0.001), IM (p < 0.01), and IO group (p < 0.01). Beneficial changes in anthropometric and body composition values were observed following all interventions with the greatest advantage seen in the IO group. The strongest correlations, of Δadiponectin with Δbody weight (r = -0.54), ΔBMI (r = -0.49), ΔFAT [%] (r = -0.48), ΔFAT [kg] (r = -0.48), and Δlean [%] (r = 0.48); and of Δleptin with Δbody weight, ΔBMI, Δwaist, Δfat, and Δlean, were documented in the IO group.. Beneficial effects were observed on serum leptin concentration, weight loss, and body composition for all interventions and in all examined groups, with the greatest advantage being associated with the orlistat treatment. Improvements in serum adiponectin concentrations resulted from the low-calorie and isocaloric diets with orlistat, but not from the isocaloric diet with metformin. We find these strategies more promising for the treatment of obesity and its related complications in obese premenopausal women.

Topics: Adiponectin; Aged; Caloric Restriction; Diet, Reducing; Female; Humans; Hypoglycemic Agents; Lactones; Leptin; Metformin; Middle Aged; Obesity; Orlistat; Postmenopause; Prospective Studies; Weight Loss

Identifying pretreatment dietary habits that are associated with weight-loss intervention outcomes could help guide individuals' selection of weight-loss approach among competing options. A pretreatment factor that may influence weight-loss outcomes is macronutrient intake.. Overweight and obese Durham Veterans Affairs outpatients were randomised to a weight-loss intervention with a low-carbohydrate diet (n = 71) or orlistat medication therapy plus a low-fat diet (n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4-day food records. Linear mixed-effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight-loss condition.. Participant's mean age was 53 years, baseline body mass index was 39.3 kg m(-2) and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss (P = 0.02) and less rapid weight regain (P = 0.03) in the low-carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low-fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain (P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition.. Selection of a weight-loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1-year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss.

Topics: Adult; Anti-Obesity Agents; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Feeding Behavior; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Gain; Weight Loss

Topics: Adult; Body Mass Index; Caloric Restriction; Combined Modality Therapy; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Lactones; Metabolome; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Testosterone; Treatment Outcome; Weight Loss; Young Adult

The current study was performed to determine the effects of cumin cyminum L. intake on weight loss and metabolic profiles among overweight subjects.. This randomized double-blind placebo-controlled clinical trial was conducted among 78 overweight subjects (male, n = 18; female, n = 60) aged 18-60 years old. Participants were randomly assigned into three groups to receive: (1) cumin cyminum L. capsule (n = 26); (2) orlistat120 capsule (n = 26) and (3) placebo (n = 26) three times a day for 8 weeks. Anthropometric measures and fasting blood samples were taken at baseline and after 8 weeks of intervention.. Consumption of the Cuminum cyminum L. and orlistat120 resulted in a similar significant decrease in weight (-1.1 ± 1.2 and -0.9 ± 1.5 vs. 0.2 ± 1.5 kg, respectively, p = 0.002) and BMI (-0.4 ± 0.5 and -0.4 ± 0.6 vs. 0.1 ± 0.6 kg/m(2), respectively, p = 0.003) compared with placebo. In addition, taking Cuminum cyminum L., compared with orlistat and placebo, led to a significant reduction in serum insulin levels (-1.4 ± 4.5 vs. 1.3 ± 3.3 and 0.3 ± 2.2 µIU/ml, respectively, p = 0.02), HOMA-B (-5.4 ± 18.9 vs. 5.8 ± 13.3 and 1.0 ± 11.0, respectively, p = 0.02) and a significant rise in QUICKI (0.01 ± 0.01 vs. -0.005 ± 0.01 and -0.004 ± 0.01, respectively, p = 0.02).. Taking cumin cyminum L. for eight weeks among overweight subjects had the same effects of orlistat120 on weight and BMI and beneficial effects on insulin metabolism compared with orlistat120 and placebo.

Topics: Adult; Biomarkers; Body Mass Index; Cuminum; Diet; Double-Blind Method; Female; Glutathione; Humans; Insulin; Iran; Lactones; Male; Metabolome; Middle Aged; Orlistat; Overweight; Oxidative Stress; Phytotherapy; Placebos; Weight Loss

Obesity is frequently present in women with the polycystic ovary syndrome (PCOS) and aggravates insulin resistance (IR) and hyperandrogenemia. We aimed to assess the effects of orlistat combined with lifestyle changes in overweight and obese women with PCOS and body mass index (BMI)-matched controls.. Prospective study.. We studied 101 women with PCOS (age 26·1 ± 6·4 years, BMI 34·5 ± 5·9 kg/m(2) ) and 29 BMI-matched women with normal ovulating cycles. All women were instructed to follow a low-calorie diet to exercise and were treated with orlistat 120 mg tid for 6 months.. Metabolic and endocrine characteristics of PCOS, blood pressure (BP) and lipid profile.. A significant and comparable reduction in BMI was observed in women with PCOS and controls. Systolic and diastolic BP decreased only in women with PCOS. Serum low-density lipoprotein cholesterol levels decreased in both women with PCOS and controls; however, this reduction was greater in controls. In contrast, serum high-density lipoprotein cholesterol levels did not change in women with PCOS and decreased in controls. Serum triglyceride levels decreased significantly and to a comparable degree in the two groups. Similarly, markers of IR improved significantly and to a comparable degree in women with PCOS and controls. Serum testosterone levels and the free androgen index decreased significantly in women with PCOS and did not change in controls.. Orlistat combined with lifestyle changes induces substantial weight loss in women with PCOS, resulting in improvements in IR, hyperandrogenemia and cardiovascular risk factors.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Caloric Restriction; Combined Modality Therapy; Exercise; Female; Humans; Lactones; Life Style; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Weight Loss; Weight Reduction Programs; 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

Reduced postprandial secretion of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence of long-term therapy with orlistat on PYYand GLP-1 release has not been studied. Our study was aimed at assessing the influence of 8-week therapy with orlistat as a component of a weight loss program on pre-prandial circulating PYY and GLP-1 levels.. Forty obese women, without concomitant diseases, were randomly allocated to groups receiving orlistat or placebo during an 8-week weight management program. Body mass, body composition and plasma levels of PYY, GLP-1 and insulin (for QUICKI calculation) were determined prior to and at the end of therapy.. Women treated with orlistat obtained significantly greater body and fat mass loss than those receiving placebo (9.0 ± 3.1 vs. 5.9 ± 3.2% and 21.9 ± 10.9 vs. 7.4 ± 15.6%, respectively). Only in those treated with orlistat a slight, but significant increase of the QUICKI was found (8.0 ± 16.5 vs. -0.1 ± 12.7 %, respectively). Weight loss was followed by a significant increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and was about 2-times greater than receiving placebo. The increase was independent of body mass changes.. The long-term inhibition of intestinal lipase by orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body mass changes. Therefore, it seems that long-term treatment with orlistat may exert hunger suppressing and insulin sensitizing incretin effect beyond weight reduction.

Topics: Body Mass Index; Body Weight; Double-Blind Method; Female; Glucagon-Like Peptide 1; Humans; Insulin; Intestinal Mucosa; Intestines; Lactones; Lipase; Obesity; Orlistat; Peptide YY; 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

Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Colon; Constipation; Cross-Sectional Studies; Diarrhea; Double-Blind Method; Finland; Humans; Incidence; Lactones; Laxatives; Obesity; Olanzapine; Orlistat; Overweight; Patient Dropouts; Prevalence; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Weight Loss

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Topics: Adult; Anti-Mullerian Hormone; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Exercise; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Luteinizing Hormone; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Testosterone; Up-Regulation; Weight Loss; Young Adult

This study was a randomized placebo-controlled trial testing the addition of orlistat to behavioral weight loss for obesity in Spanish-speaking-only Latino/as with versus without binge eating disorder (BED) performed at a community mental health center serving educationally- and economically-disadvantaged patients. Latino/as have high rates of obesity but are under-represented in obesity treatment studies and despite comparable-to-or-higher rates of BED than Whites, Latino/as are under-represented in BED treatment studies. BED is associated with obesity but whether it predicts/moderates treatment outcomes remains uncertain. Thus, this study also tested whether BED prospectively predicts/moderates outcomes.. Seventy-nine obese Spanish-speaking-only Latino/as with BED (N=40) versus without BED (N=39) at a community mental health center were randomly assigned to four-months of orlistat-plus-BWL or placebo-plus-BWL. BWL was culturally-enhanced modification of Diabetes-Prevention-Program delivered in weekly sessions in Spanish. Orlistat (120 mg tid) and matching-placebo delivered with standard clinical-management. Participants were assessed independently throughout treatment, post-treatment, and six-month follow-up.. 78% completed treatments; completion rates did not differ significantly by medication or BED. Intent-to-treat mixed-models analyses revealed significant improvements in binge eating, eating-psychopathology, and depression, and significant--albeit modest--weight-loss. Overall, the addition of orlistat to BWL was not associated with greater improvements; however, BED moderated weight-loss: orlistat-plus-BWL produced significantly greater weight-loss in non-BED group but not in BED. Improvements were maintained through 6-month follow-up; BED significantly predicted/moderated increases in eating concerns and depression following treatment. Within BED-group, binge-eating remission rates were 65% (post-treatment) and 50% (follow-up).. In this controlled trial performed at community mental health center serving educationally- and economically-disadvantaged Spanish-speaking-only Latino/as with co-morbid psychiatric needs, we observed outcomes for the BWL plus orlistat/placebo medication that approximate or are slightly dampened relative to the literature for efficacy trials with much more restrictive obese and BED samples. In this complex patient group, adding orlistat to BWL produced greater weight-loss than adding placebo among obese patients without BED but not among those with BED. Although 50% of BED patients maintained abstinence from binge-eating following these specific obesity treatments (BWL plus orlistat/placebo), BED was a negative prognostic indicator for some outcome variables.. clinicaltrials.gov Identifier: NCT00516919.

Topics: Adult; Aged; Anti-Obesity Agents; Binge-Eating Disorder; Community Mental Health Centers; Female; Health Behavior; Hispanic or Latino; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Poverty Areas; Treatment Outcome; Weight Loss; Young Adult

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

Examining predictors of blood-pressure (BP) response to weight-loss diets might provide insight into mechanisms and help guide clinical care. We examined whether certain baseline patient characteristics (e.g. diet, medical history and laboratory tests) predicted BP response to two weight-loss diet approaches that differ in macronutrient content. One hundred and forty-six overweight adult outpatients were randomized to either a low-carbohydrate diet (N = 72) or orlistat plus a low-fat diet (N = 74) for 48 weeks. Predictors of BP reduction were evaluated using a structured approach and random effects regression models. Participants were 56% African-American, 72% male and 53 (±10) years-old. Of the variables considered, low baseline high-density lipoprotein (HDL) predicted greater reduction in BP in those patients who received the low-carbohydrate diet (p = 0.03 for systolic BP; p = 0.03 for diastolic BP and p = 0.02 for mean arterial pressure). A low HDL level may identify patients who will have greater BP improvement on a low-carbohydrate diet.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Pressure; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Female; Humans; Lactones; Lipoproteins, HDL; Male; Middle Aged; Obesity; Orlistat; Weight Loss; Young Adult

Patients undergoing gastric bypass surgery are usually required to lose weight during the preoperative phase of their management. For some individuals, this is difficult to achieve with diet and exercise alone, and the use of weight loss medication may be considered a treatment option.. To evaluate the use of orlistat 60 mg taken up to 3 times daily as an adjunct to achieve the 10% preoperative weight loss recommended in this bariatric program prior to gastric bypass surgery.. The aim was to recruit 50 patients (25 treatment, 25 controls) who were in the preoperative phase of their bariatric program. Patients were referred by their physician. Control subjects were selected from individuals who were eligible but not interested in participating in the study during the same period. All patients received usual care.. Nineteen patients (5 males) and 19 age- and sex-matched controls were included. The mean (SD) initial body mass index for the treatment versus control group was, respectively, 49.5 (10.5) versus 47.2 (4.9) kg/m(2) (p = 0.559). At 3 months, the percent excess weight (EW) loss was 2.4 (3.8) (n = 15) versus 5.5 (7.6) (n = 19) (p = 0.111) and the percent total body weight (TBW) loss was 1.2 (1.9) versus 2.9 (4.1) (p = 0.103). At 6 months, the percent EW loss was 3.6 (6.4) (n = 9) versus 10.2 (8.0) (n = 16) (p = 0.036) and the percent TBW loss was 2.0 (3.4) versus 5.4 (4.2) (p = 0.048).. Some patients felt that orlistat was beneficial for weight loss; however, overall, they did not show benefit from its addition to their preoperative weight loss management.

Topics: Adult; Anti-Obesity Agents; Bariatric Surgery; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Preoperative Care; Weight Loss

A higher body mass index is associated with exercise-related injuries and increased risk for musculoskeletal and connective tissue disorders, which are relevant to military personnel. Studies show the efficacy of orlistat 60 mg for promoting weight and body fat loss in civilians; however, its efficacy among predominantly young, male soldiers is unknown. This study's objective was to examine the effect of a 6-month, standard education-based weight-management program with and without orlistat 60 mg on changes in weight and body fat in overweight soldiers. Data were collected for this randomized, controlled trial from March 2008 to November 2010 at Fort Bragg, NC. Participants were enrolled in an education-based weight management program (n=435; 75% men) and were randomized to placebo or orlistat 60 mg, three capsules daily with meals. All participants were recommended to maintain a reduced-energy, low-fat diet. Among study completers (14% retention rate; placebo n=22, orlistat n=35) members of both groups lost significant weight from baseline (placebo -3.0±5.2 kg; orlistat -3.2±4.7 kg; P<0.01), but only the orlistat group lost fat mass (-2.5±3.9 kg; P<0.001), whereas the placebo group lost lean mass (-1.4±2.7 kg; P <0.01). An intent-to-treat analysis (?1 follow-up body weight measure) demonstrated that the orlistat group lost more fat mass vs the placebo group (-1.3±2.9 kg vs ?0.6±1.8 kg, respectively; P<0.05), but less lean mass (-0.2±2.0 kg vs -0.8±1.8 kg, respectively; P<0.01). Orlistat 60 mg may be an effective adjunct to an education-based weight management program in a mostly young, male soldier population.

Topics: Adipose Tissue; Anthropometry; Anti-Obesity Agents; Body Composition; Body Mass Index; Diet, Fat-Restricted; Diet, Reducing; Exercise; Female; Health Education; Humans; Lactones; Male; Obesity; Orlistat; Treatment Outcome; Weight Loss

To explore long-term effects of orlistat in adult clozapine- or olanzapine-treated patients with DSM-IV-diagnosed schizophrenia and overweight or obesity who tolerate orlistat.. Orlistat or placebo was added to clozapine or olanzapine in stable doses in a 16-week randomized controlled trial. Open-label orlistat was added to the antipsychotics during a 16-week extension phase for those completing the double-blind phase. No low-calorie diet or participation in behavioral programs was required. Body weight (primary outcome) and some metabolic parameters were measured prospectively. Analyses were performed for those completing both phases (ie, population differing from that reported earlier). The study was conducted from 2004 through 2005.. During the open-label phase, the 44 patients experienced mean ± SD body weight loss of -1.29 ± 3.04 kg, P = .007. During both phases, men (but not women) showed a weight loss of -2.39 ± 5.45 kg, P = .023. Some subgroups showed desirable changes in several metabolic parameters. Prolonged (32 weeks) orlistat treatment yielded no additional benefits as compared to short (16 weeks) treatment.. In clozapine- or olanzapine-treated overweight or obese patients able to take orlistat on a long-term basis, the drug, with no concomitant hypocaloric diet or behavioral interventions, caused moderate weight loss only in men. However, some metabolic benefits may be achieved independently of weight changes. In patients who do not respond to orlistat within the first 16 weeks, continuation treatment may provide no additional benefits.. controlled-trials.com Identifier: ISRCTN65731856.

Topics: Adult; Anti-Obesity Agents; Antipyretics; Benzodiazepines; Cholesterol; Cholesterol, LDL; Clozapine; Double-Blind Method; Female; Humans; Lactones; Male; Obesity; Olanzapine; Orlistat; Schizophrenia; Sex Factors; Treatment Outcome; Weight Loss

Pharmacotherapy, associated with a comprehensive weight loss intervention, has emerged as a promising therapeutic approach in adolescents. Identification of subjects who best respond to a pharmacological intervention remains difficult.. To compare the value of early weight loss after 12 weeks of treatment with placebo or orlistat (120 mg three times a day) in predicting treatment outcome after 52 weeks.. Secondary analysis of a randomized control trial in 182 placebo-treated and 357 orlistat-treated obese adolescents (Body mass index [BMI] ≥ 2 kg/m(2) above the 95(th) percentile).. Percent weight change at 12 weeks was positively correlated with percent change in weight (r(2) ≥ 0.41), BMI (r(2) ≥ 0.33) and waist circumference (r(2) ≥ 0.20) at 52 weeks in both the placebo and orlistat groups (P < 0.001). A weight loss ≥ 5% of baseline weight at 12 weeks was associated with a mean weight loss of 8.1% (95% CI: 6.4 to 9.7) at the study end that was independent of treatment. Subjects in the orlistat group were 2.44 times (95% CI: 1.34 to 4.46) more likely to experience a weight loss ≥ 5% after 12 weeks than subjects in the placebo group (P = 0.0028).. Early weight loss predicts a favourable outcome in both placebo-treated and orlistat-treated subjects but is more than 2 times more likely to occur in the orlistat group. Addition of orlistat should be considered as part of a weight loss intervention but reevaluated after 3 months of treatment.

Topics: Adolescent; Anti-Obesity Agents; Body Mass Index; Female; Humans; Lactones; Male; Obesity; Orlistat; Retrospective Studies; Single-Blind Method; Treatment Outcome; Weight Loss

Obesity is associated with an altered GH/IGF-I axis status, accounting for the increased cardiovascular risk in obese subjects with GH deficiency. Aim of this randomized, simple-blind, cross-over study was to verify the effectiveness of a short-term treatment with orlistat in reducing non-esterified fatty acid (NEFA) and influencing the endogenous activity of GH/IGF-I axis in obese subjects.. The primary outcome measures were post-prandial lipemia; GH peak after GHRH+arginine; IGF-I; IGF-binding protein (BP)-3, IGF-I/IGFBP-3 ratio. Secondary outcome measures were insulin resistance (IR) indexes (homeostasis model assessment of insulin resistance and Insulin Sensitivity Index).. Twenty obese post-menopausal women (age: 53.6 ± 6.2; body mass index: 34.1 ± 4.0) were randomized to receive normo-caloric diet plus + orlistat (Roche, UK; 120 mg tid) or normo-caloric diet without the additional treatment. The duration of follow-up was 10 days for each treatment period.. Orlistat induced a weight-independent reduction in post-prandial NEFA levels compared with diet alone, with higher GH peak, IGF-I, and IGF-I/IGFBP3 ratio. GH peak was correlated negatively with postprandial NEFA and positively with IGF-I and IGF-I/IGFBP-3 ratio.. Orlistat is effective in inducing a weight-independent higher reduction in post-prandial NEFA levels than dietary treatment alone along with increase in GH peak, IGF-I levels, and IGFI/ IGFBP-3 ratio. These results might add a new potential benefit of orlistat in the management of obese subjects.

Topics: Anti-Obesity Agents; Cross-Over Studies; Diet; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Lactones; Middle Aged; Obesity; Orlistat; Single-Blind Method; Treatment Outcome; Weight Loss

It is well established that combining a reduced calorie, low-fat diet with the lipase inhibitor orlistat results in significantly greater weight loss than placebo plus diet. This weight loss is accompanied by changes in adipose tissue (AT) distribution. As 60 mg orlistat is now available as an over-the-counter medication, the primary objective of this study was to determine whether 60 mg orlistat is effective as a weight loss option in a free-living community population with minimal professional input.. AT and ectopic lipid content were measured using magnetic resonance imaging and (1)H MR spectroscopy, respectively, in 27 subjects following 3 months treatment with orlistat 60 mg and a reduced calorie, low-fat diet.. Significant reductions in intra-abdominal AT (-10.6%, P=0.023), subcutaneous (-11.7% P<0.0001) and pericardial fat (-9.8%, P=0.034) volumes and intrahepatocellular lipids (-43.3%, P=0.0003) were observed. These changes in body fat content and distribution were accompanied by improvements in plasma lipids and decreases in blood pressure and heart rate.. These findings suggest that over-the-counter 60 mg orlistat, in combination with the type of advice a subject could expect to be given when obtaining 60 mg orlistat in a community setting, does indeed result in potentially clinically beneficial changes in body composition and risk factors for metabolic diseases.

Topics: Abdominal Fat; Adiposity; Adult; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Diet, Fat-Restricted; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Lipid Metabolism; Lipids; Liver; Male; Middle Aged; Nonprescription Drugs; Obesity, Abdominal; Orlistat; Overweight; Weight Loss; Young Adult

It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P < 0.05). In addition, orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P < 0.05), total fat mass loss (-4.65 kg vs. -3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo-treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.

Topics: Adiposity; Adult; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Intra-Abdominal Fat; Lactones; Lipase; Liver; Male; Middle Aged; Muscles; Orlistat; Overweight; Time Factors; Tomography, X-Ray Computed; Weight Loss

The objective of this multicenter, randomized, double-blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2-week run-in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA(1c)) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.

Topics: Adolescent; Adult; Aged; Benzoxazines; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Intention to Treat Analysis; Lactones; Lipase; Male; Metformin; Middle Aged; Obesity; Orlistat; Patient Selection; Treatment Outcome; Weight Loss

Obesity increases the comorbidity-adjusted relative risk of developing end-stage renal disease. Body mass index (BMI) > 30 kg/m(2) was a contraindication for transplant in our renal unit until 2008.. Open-label prospective nonrandomized intervention.. All men and women aged 18-75 years with chronic kidney disease (CKD) and BMI > 30 or > 28 kg/m(2) with diabetes, hypertension, or dyslipidemia and otherwise suitable for kidney transplant if on dialysis therapy were eligible to enroll in the weight-management program. 64 patients were referred; 44 agreed to participate in the intervention group and 20 did not wish to take part and constitute the usual-care group.. 24-month weight-management program that included a low-fat renal-specific diet, exercise, and orlistat, 120 mg, 3 times daily.. Body weight, blood pressure (BP), kidney transplant wait listing.. Body weight, BP, estimated glomerular filtration rate (eGFR; calculated using the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation).. 32 patients (73%) in the weight-management program group completed the follow-up evaluation. Baseline mean BMI was 35.7 +/- 4.5 (SD) kg/m(2) in the weight-management program group and 34.1 +/- 4.2 kg/m(2) in the usual-care group. 12 (38%) patients in the weight-management program and 9 (45%) in usual care had stages 3-4 CKD, with the remainder in stage 5 CKD on dialysis therapy. There were no differences in body weight, BP, or eGFR between groups at baseline. After 24 months, mean body weight was 94.6 +/- 16.1 kg in the weight-management program group versus 101.0 +/- 26.8 kg in the usual-care group (P < 0.001), and eGFR was 43 mL/min in the weight-management program group versus 18 mL/min in the usual-care group (P < 0.001). 9 of 26 (35%) otherwise eligible patients in the weight-management program and 1 of 18 (6%) patients in usual care were accepted for kidney transplant listing, with 3 transplants performed in the weight-management program group and 1 in the usual-care group.. Nonrandomized trial, small number of participants.. The weight-management program group showed significant weight loss and weight-loss maintenance in obese patients with CKD and potentially enables obese patients with CKD to undergo kidney transplant.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Body Mass Index; Diet; Dose-Response Relationship, Drug; Exercise Therapy; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Lactones; Lipase; Male; Middle Aged; Nutritional Status; Obesity; Orlistat; Patient Education as Topic; Prospective Studies; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), are available to the public but, to our knowledge, have never been compared.. Overweight or obese outpatients (n = 146) from the Department of Veterans Affairs primary care clinics in Durham, North Carolina, were randomized to either LCKD instruction (initially, <20 g of carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus low-fat diet instruction (<30% energy from fat, 500-1000 kcal/d deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters.. The mean age was 52 years and mean body mass index was 39.3 (calculated as weight in kilograms divided by height in meters squared); 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Weight loss was similar for the LCKD (expected mean change, -9.5%) and the O + LFD (-8.5%) (P = .60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs 1.5 mm Hg) and diastolic (-4.5 vs 0.4 mm Hg) blood pressures (P < .001 for both comparisons). High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups. Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A(1c) levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant.. In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters and was more effective for lowering blood pressure.. clinicaltrials.gov Identifier: NCT00108524.

Topics: Adult; Anti-Obesity Agents; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Visceral adipose tissue-derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12-week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMA(IR)). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMA(IR) group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMA(IR) group was positively correlated with change in BMI and negatively correlated with initial HOMA(IR) level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMA(IR) group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Female; Hip; Humans; Insulin Resistance; Lactones; Life Style; Longitudinal Studies; Male; Obesity; Orlistat; Serpins; Treatment Outcome; Waist Circumference; Weight Loss

The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index = >or=27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 +/- 9.0 (standard deviation) years and mean body mass index was 36.4 +/- 6.3 kg/m(2). Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of >or=5% body weight (n = 24) compared to <5% body weight (n = 17) correlated with improvement in insulin sensitivity (P = 0.001) and steatosis (P = 0.015). Comparing subjects who lost >or=9% of body weight (n = 16), to those that did not (n = 25), improved insulin sensitivity (P < 0.001), adiponectin (P = 0.03), steatosis (P = 0.005), ballooning (P = 0.04), inflammation (P = 0.045), and nonalcoholic fatty liver disease activity score (P = 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P = 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >or=5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >or=9% also achieved improved hepatic histologic changes.

Topics: Adult; Anti-Obesity Agents; Diet, Reducing; Fatty Liver; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Treatment of obesity-related anovulation poses a significant clinical challenge. Occasionally, the use of antiobesity medications such as orlistat or insulin sensitizing agents such as metformin is sometimes indicated in these patients. This study aimed to compare the effects of metformin and orlistat for improving ovulation in obese anovulatory women.. This was an open-label RCT. A total of 40 women were randomized to receive either metformin (n = 20) or orlistat (n = 20). BMI as well as the androgen profile and the ovulatory status were assessed at baseline and at four weekly intervals for 3 months. Different anthropometric and endocrine parameters were also assessed as possible predictors of ovulation.. There was no significant difference between the two study arms regarding the ovulation rate for metformin and orlistat [40% (n = 8/20) and 25% (n = 5/20), respectively, P = 0.31]. Both arms showed a significant drop in the BMI, testosterone and androstendione concentrations (P < 0.05), but there was no difference between the two arms. Patients who ovulated had significantly lower concentrations of baseline LH, androstendione, dehydroepiandrosterone and free androgen index (P < 0.05). Among these factors, a low baseline LH was found to be the only independent predictor of ovulation (area under curve, 0.85).. Both metformin and orlistat show a similar effect on weight loss, ovulation rates and androgen concentrations. However, the effects on ovulation rates need to be confirmed in larger studies. The presence of a low baseline serum LH was found to be the most important predictor of ovulation. The study was registered at clinicaltrials.gov. NCT00292799.

Topics: Adolescent; Adult; Androgens; Anovulation; Anti-Obesity Agents; Female; Humans; Hypoglycemic Agents; Lactones; Luteinizing Hormone; Metformin; Obesity; Orlistat; Ovulation; Weight Loss; Young Adult

Orlistat is a lipase inhibitor that reduces the intestinal absorption of fat and may enhance the effects of dietary and behavioural therapy on weight loss and maintenance. The present study examined the effect of orlistat on dietary intake, especially fat intake, during long-term weight maintenance.. Subjects comprised 44 men and women (aged 18-63 years; body mass index 37.5 +/- 4.3 kg m(-2)) included in the Scandinavian Multicenter study of Obese subjects with the metabolic syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week, very low energy diet (VLED). Two months after the end of the trial when the use of orlistat was optional, 33 subjects remained in the study. A dietary interview based on a validated food frequency questionnaire was conducted before the VLED, after 1 year of treatment with orlistat or placebo and 2 months after the end of the trial.. At 1 year, dietary intake did not differ between the orlistat and placebo group. Energy percent (E%) fat was reduced and E% carbohydrate was increased within both groups. Two months after the end of the trial, E% fat was 32.6% (SD 6.2%) in subjects that chose to take orlistat and 27.7% (SD 5.5%) in subjects not taking orlistat [between group difference -5.0% (95% confidence interval -9.2 to -0.7); P = 0.021].. The use of orlistat compared with placebo in a lifestyle modification programme does not appear to influence dietary intake. Subjects that chose to take orlistat after the end of the programme did not comply with dietary recommendations and this may hamper the effect of the drug.

Topics: Adolescent; Adult; Anti-Obesity Agents; Combined Modality Therapy; Diet, Reducing; Dietary Fats; Energy Intake; Female; Humans; Lactones; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Patient Compliance; Treatment Outcome; Weight Loss; Young Adult

Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss.. 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods.. Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Topics: Adiponectin; Adipose Tissue; Anti-Obesity Agents; Apelin; Biomarkers; Blood Glucose; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Female; Ghrelin; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Interleukin-6; Lactones; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Placebos; Tumor Necrosis Factor-alpha; Weight Loss

The objective of the study was to investigate the effect of long-term (3.2 years) weight loss on serum levels of the nontraditional cardiovascular risk factors interleukin (IL)-18 and matrix metalloproteinase (MMP)-9. Moreover, we wanted to assess the significance of the magnitude of the weight loss and evaluate the potential effects of 36 months of treatment with the lipase inhibitor orlistat on these parameters. Sixty-eight abdominally obese subjects completed 8 weeks of very low energy diet (600-800 kcal/d) followed by 36 months of randomized treatment with either orlistat or placebo together with lifestyle intervention. Serum levels of IL-18, MMP-9, and leptin were measured by flowmetric xMAP technology (Luminex, Austin, TX). Changes in the levels of IL-18, MMP-9, and leptin were similar in the orlistat and the placebo group during this study. Thus, the 2 groups were combined for further analysis. A weight loss of 8.4 +/- 8.8 kg from baseline to 3.2 years was associated with significant decreases in IL-18 (P < .001), MMP-9 (P < .01), and leptin (P < .001). Matrix metalloproteinase-9 was, however, significantly increased after 8 weeks of very low energy diet-induced weight loss (P < .05). The long-term changes in IL-18 were significantly associated with changes in body mass index independent of changes in blood pressure and lipids (P < .05). Levels and changes of IL-18 and MMP-9 were significantly positively associated at 3.2 years (P < .01). Long-term changes in leptin were significantly associated with changes in IL-18 (P < .01) at 3.2 years. Diet-induced long-term weight loss decreased IL-18 and MMP-9. The decrease in IL-18 was associated with changes in body mass index independent of changes in blood pressure and lipids, indicating that even a minor weight reduction (>5%) has beneficial effects on nontraditional cardiovascular risk markers. Orlistat treatment had no independent effects on IL-18, MMP-9, or leptin in the present study.

Topics: Adolescent; Adult; Anti-Obesity Agents; Blood Pressure; Cholesterol; Double-Blind Method; Female; Humans; Interleukin-18; Lactones; Leptin; Linear Models; Male; Matrix Metalloproteinase 9; Middle Aged; Obesity; Orlistat; Triglycerides; Waist Circumference; Weight Loss; Young Adult

The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. We assessed the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes.. We did a double-blind, placebo-controlled 20-week trial, with open-label orlistat comparator in 19 sites in Europe. 564 individuals (18-65 years of age, body-mass index 30-40 kg/m2) were randomly assigned, with a telephone or web-based system, to one of four liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg, n=90-95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial, including the 2-week run-in. Weight change analysed by intention to treat was the primary endpoint. An 84-week open-label extension followed. This study is registered with ClinicalTrials.gov, number NCT00422058.. Participants on liraglutide lost significantly more weight than did those on placebo (p=0.003 for liraglutide 1.2 mg and p<0.0001 for liraglutide 1.8-3.0 mg) and orlistat (p=0.003 for liraglutide 2.4 mg and p<0.0001 for liraglutide 3.0 mg). Mean weight loss with liraglutide 1.2-3.0 mg was 4.8 kg, 5.5 kg, 6.3 kg, and 7.2 kg compared with 2.8 kg with placebo and 4.1 kg with orlistat, and was 2.1 kg (95% CI 0.6-3.6) to 4.4 kg (2.9-6.0) greater than that with placebo. More individuals (76%, n=70) lost more than 5% weight with liraglutide 3.0 mg that with placebo (30%, n=29) or orlistat (44%, n=42). Liraglutide reduced blood pressure at all doses, and reduced the prevalence of prediabetes (84-96% reduction) with 1.8-3.0 mg per day. Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment.. Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes.. Novo Nordisk A/S, Bagsvaerd, Denmark.

Topics: Analysis of Variance; Anti-Obesity Agents; Body Mass Index; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Female; Glucagon-Like Peptide 1; Humans; Injections, Subcutaneous; Lactones; Liraglutide; Logistic Models; Male; Obesity; Orlistat; Prediabetic State; Safety; Treatment Outcome; Waist Circumference; Weight Loss

Obesity, characterized by hyperleptinemia and hypoghrelinemia, has become a major health problem all over the world and is associated with an increased risk of complications including insulin resistance, hypertension, dyslipidemia, diabetes mellitus and atherosclerosis. The use of the pancreatic lipase inhibitor Orlistat can help seriously overweight people to achieve and maintain weight loss. The aim of our study was to compare the serum leptin and ghrelin levels in obese subjects who take orlistat with those receiving only dietary treatment. Twenty-one obese patients and 10 control subjects participated. The obese patients were divided into two groups; one group (n=11) took orlistat (120 mg, 3 times daily) and received dietary treatment and the other (n=10) only received the dietary treatment. The study lasted twelve weeks. The concentrations of serum ghrelin, leptin, insulin and C-peptide, and routine biochemical parameters, were measured in both groups. The serum ghrelin level was higher in control (183+/-62 fmol/ml) than obese (59+/-30 fmol/ml) subjects while the plasma leptin level was lower in control (8.7+/-12 microg/L) than obese (36.7+/-19 microg/L) subjects (all p<0.001). BMI and the total blood cholesterol, LDL and triglyceride levels fell significantly after both orlistat and dietary treatment in the obese subjects (all p<0.01), and the plasma ghrelin level rose (p<0.01). The leptin level demonstrated the opposite trend in both groups but only the patients taking orlistat showed a significant change (p<0.05).Taken together, these results show that orlistat has no effect on body weight in obese subjects additional to that conferred by a non-pharmacological life-style intervention. We therefore conclude that weight lost rather than type of treatment might be more valuable in obesity.

Topics: Adult; Anti-Obesity Agents; Diet, Reducing; Enzyme Inhibitors; Female; Ghrelin; Humans; Lactones; Leptin; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Weight Loss

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

To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome.. Prospective clinical study.. Department of obstetrics and gynecology in a major university in Greece.. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women.. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks.. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured.. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester.. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.

Topics: 17-alpha-Hydroxyprogesterone; Androgens; Androstenedione; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Caloric Restriction; Case-Control Studies; Combined Modality Therapy; Dehydroepiandrosterone Sulfate; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Lactones; Luteinizing Hormone; Obesity; Orlistat; Polycystic Ovary Syndrome; Prolactin; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Treatment Outcome; Weight Loss

To investigate the effects of: I) short- (8 weeks), II) long-term (3 years) weight loss, and III) the degree of weight loss on circulating levels of adiponectin, high sensitive-C reactive protein (hs-CRP), and fibrinogen in obese subjects. Moreover, to evaluate the effect of the lipase inhibitor, orlistat, on these parameters.. Weight loss induced in 93 obese subjects (mean weight: 108.9+/-15.8 kg) through 8-week very-low-energy diet (VLED, 800 kcal/day) followed by randomization to orlistat or placebo together with lifestyle intervention for further 3 years. Adiponectin and hs-CRP were measured at baseline, after 8 weeks of VLED and 6, 12, and 36 months after the VLED by flowmetric xMAP technology (Luminex Multi-Analyte Profiling System, Luminex Corp., Austin, TX, USA). Fibrinogen was measured in a coagulation assay.. Weight loss after VLED treatment was 14.3+/-4.5 kg and after 3 years 7.7+/-8.7 kg. Orlistat-treated subjects regained 3.9 kg less than placebo-treated from the end of the VLED to 3 years (P=0.01). No differences were detected between the two groups regarding changes in adiponectin, hs-CRP, or fibrinogen. Accordingly, the groups were combined for further analyses. Serum adiponectin increased by 22% (P<0.05) after the VLED but returned to baseline after 3 years. Both short- and long-term weight losses needed to be in excess of 10% (approximately 12 kg) in order to increase adiponectin levels significantly. Weight loss was associated with a significant decrease in hs-CRP. Fibrinogen decreased by 12% (P<0.05) after 3 years.. In obese subjects, weight loss was associated with an increase in serum adiponectin and a decrease in hs-CRP and plasma fibrinogen. Long-term weight loss (3 years) must exceed 10% to induce a combined significant improvement in these inflammatory markers.

Topics: Abdominal Fat; Adiponectin; Adult; Aged; Anti-Obesity Agents; Biomarkers; C-Reactive Protein; Diet, Reducing; Double-Blind Method; Energy Intake; Enzyme Inhibitors; Female; Fibrinogen; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Scandinavian and Nordic Countries; Time Factors; Weight Loss

The study was conducted to provide information on how consumers would use orlistat 60 mg, especially in terms of product dosing, in a setting without physician supervision.. A 3-month, open-label, naturalistic study was conducted in an over-the-counter (OTC) setting in 18 pharmacies. Consumers >/=18 years were allowed to purchase orlistat packages containing a bottle of orlistat 60 mg plus educational materials, which provided lifestyle information and tools to encourage successful weight loss. Data were collected at pharmacy visits and during telephone interviews at 14, 30, 60, and 90 days after enrollment.. A total of 237 subjects purchased and used the product, and completed at least one interview. Most subjects followed the dosing directions and took two to three capsules per day with meals throughout the study. The majority of subjects took a daily multivitamin, as directed. Approximately, 80% of subjects used the educational materials and found them useful or very useful. Over the study duration, most subjects reported following a diet and 51% of subjects reported more frequent or longer exercise than at enrollment. Approximately, 80% of subjects indicated they were satisfied or very satisfied with the weight loss achieved; measured and self-reported relative median weight loss was approximately 5% after > or =60 days of using orlistat. Most common adverse events were gastrointestinal (GI), and majority of subjects did not interrupt or discontinue orlistat due to these GI events.. These results demonstrate that orlistat 60 mg can be used appropriately and safely and with high consumer satisfaction without physician supervision or dietary counseling. Collectively, results indicate that orlistat 60 mg is an appropriate weight loss therapy in the OTC environment.

Topics: Adult; Anti-Obesity Agents; Consumer Product Safety; Drug Administration Schedule; Drug Labeling; Exercise; Female; Health Behavior; Health Knowledge, Attitudes, Practice; Humans; Lactones; Male; Middle Aged; Nonprescription Drugs; Obesity; Orlistat; Patient Compliance; Patient Education as Topic; Patient Satisfaction; Time Factors; Treatment Outcome; United States; Vitamins; Weight Loss

To examine the effect of orlistat on dietary restraint, disinhibition, hunger, and binge eating and to understand the relation between changes in eating behavior and weight maintenance.. Subjects were 306 women and men (age: 19-45 years; BMI: 37.5 +/- 4.1 kg/m(2)) included in the Scandinavian Multicenter study of Obese subjects with the Metabolic Syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week very low energy diet (VLED). Outcomes were changes in weight and in the Three Factor Eating Questionnaire (TFEQ) and Binge Eating Scale (BES) between screening and 17 and 33 months after randomization. As reported previously, weight gain following VLED was lower in subjects treated with orlistat than with placebo.. Compared to screening results, dietary restraint was increased and disinhibition, hunger, and binge eating were decreased in both groups. These changes were similar in both groups with the exception of the hunger score at month 33 that was reduced more in the placebo than in the orlistat group (difference between groups -1.1 (95% CI (-2.0, -0.2)) P = 0.014). In multivariate analyses, scores for restraint, disinhibition and binge eating were associated with weight loss after adjustment for BMI, gender, age, and treatment (all P < or = 0.002, model R (2) = 0.12-0.17).. Orlistat did not affect eating behavior differently in any substantial way than the placebo did in this long-term weight maintenance trial. The results indicate that increased restraint and decreased disinhibition and binge eating are important for sustained weight maintenance in obese subjects with the metabolic syndrome.

Topics: Adult; Anti-Obesity Agents; Body Weight; Bulimia; Energy Intake; Feeding Behavior; Female; Humans; Lactones; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Orlistat; Regression Analysis; Scandinavian and Nordic Countries; Weight Loss

Topics: Adult; Anti-Obesity Agents; Fatty Liver; Female; Humans; Lactones; Liver Cirrhosis; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

To assess changes in body composition with weight loss in obese subjects randomized to a laparoscopic adjustable gastric band surgical program or a medical program using a very-low-energy diet and orlistat.. Using body composition measurements by DXA, neutron activation for total body nitrogen, and whole body gamma counting for total body potassium, we studied changes in fat mass, fat distribution, fat-free mass, total bone mineral content, total body protein, and body cell mass at 6 (n = 61 paired) and 24 months (n = 53 paired) after randomization.. At 24 months, the surgical group had lost significantly more weight (surgical, 20.3 +/- 6.5 kg; medical, 5.9 +/- 8.0 kg). There was favorable fat-free mass to fat mass loss ratios for both groups (surgical, 1:5.5; medical, 1:5.9). Changes in total body nitrogen or potassium were favorable in each group. A small reduction in mean bone mineral content occurred throughout the study but was not associated with extent of weight loss or treatment group. At 6 months, weight loss for both groups was similar (surgical, 14.1 +/- 4.5 kg; medical, 13.3 +/- 7.3 kg). The medical program subjects lost less fat-free mass and skeletal muscle and had increased total body protein. The proportion of body fat to limb fat remained remarkably constant throughout the study.. Weight loss programs used in this study induced fat loss without significant deleterious effects on the components of fat-free mass.

Topics: Adult; Appetite Depressants; Body Composition; Diet, Reducing; Female; Gastric Bypass; Humans; Lactones; Male; Middle Aged; Muscle, Skeletal; Obesity; Orlistat; Weight Loss

It is important to find ways to predict response to treatments as this may inform treatment planning. We examined rapid response in obese patients with binge eating disorder (BED) who participated in a randomized placebo-controlled study of orlistat administered with cognitive behavioral therapy delivered by guided self-help (CBTgsh) format.. Fifty patients were randomly assigned to 12-week treatments of either orlistat+CBTgsh or placebo+CBTgsh, and were followed in double-blind fashion for 3 months after treatment discontinuation. Rapid response, defined as 70% or greater reduction in binge eating by the fourth treatment week, was determined by receiver operating characteristic curves, and was then used to predict outcomes.. Rapid response characterized 42% of participants, was unrelated to participants' demographic features and most baseline characteristics, and was unrelated to attrition from treatment. Participants with rapid response were more likely to achieve binge eating remission and 5% weight loss. If rapid response occurred, the level of improvement was sustained during the remaining course of treatment and the 3-month period after treatment. Participants without rapid response showed a subsequent pattern of continued improvement.. Rapid response demonstrated the same prognostic significance and time course for CBTgsh as previously documented for individual CBT. Among rapid responders, improvements were well sustained, and among non-rapid responders, continuing with CBTgsh (regardless of medication) led to subsequent improvements.

Topics: Adult; Anti-Obesity Agents; Bulimia Nervosa; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Female; Follow-Up Studies; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Prognosis; Self Care; Time Factors; 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 examine the efficacy of a lifestyle modification programme in weight maintenance for obese subjects after cessation of treatment with Orlistat.. Fifty-five subjects with and without diabetes mellitus were randomized to a lifestyle modification programme or to usual care at the end of 6 months' treatment with Orlistat. The intervention programme was nutritionist led, consisting of components of dietary management, physical activity, peer group support and discussion using techniques of self-monitoring, stimulus control and cognitive restructuring. Anthropometric indices, body composition, basal metabolic rate, blood pressure, fasting glucose, glycosylated haemoglobin, lipid profile, 24-hour urinary albumin excretion, dietary intake, physical activity level, and quality of life were assessed before and after the intervention period. Results Subjects in the intervention group maintained their weight loss and favourable anthropometric, metabolic, dietary intake, physical activity and quality of life profiles, while most parameters deteriorated in the usual care group, being more marked in subjects with diabetes. The magnitude of weight gain was comparable to that lost during Orlistat treatment.. A specially designed nutritionist-led lifestyle modification programme for obese subjects is effective in weight maintenance after treatment with Orlistat, in the absence of which the benefits of drug treatment were lost. The magnitude of the effect of lifestyle modification is comparable to that observed with Orlistat.

Topics: Adolescent; Adult; Albuminuria; Anti-Obesity Agents; Basal Metabolism; Blood Glucose; Blood Pressure; Body Composition; Body Weight; Cognitive Behavioral Therapy; Diabetes Complications; Enzyme Inhibitors; Exercise; Fasting; Follow-Up Studies; Glycated Hemoglobin; Humans; Lactones; Lipase; Lipids; Middle Aged; Obesity; Orlistat; Quality of Life; Risk Reduction Behavior; Self Care; Social Support; Weight Loss

To assess the impact of weight reduction on serum adipocytokines, C-reactive protein (CRP), and insulin sensitivity in hypertensive female patients with central obesity.. This study was performed using the database and stored serum samples of female patients who had participated in an intervention study focused on weight loss. Thirty hypertensive women aged 18 to 65, body mass index (BMI) > 27 kg/m2, and central obesity were selected. They were randomly assigned to receive either a low-calorie diet plus orlistat 120 mg three times daily or a low-calorie diet alone for 16 weeks. Patients who experienced weight loss greater than 5% (n = 24) were assessed for blood pressure, anthropometric parameters, visceral fat, insulin resistance (HOMA-R - homeostasis model assessment of insulin resistance) and sensitivity (ISI - Insulin Sensitivity Index) indices, plus serum lipids, adipocytokines (adiponectin, leptin, IL-6, and TNF-alpha) and CRP levels.. After BMI had been reduced by approximately 5% in both groups, visceral fat, fasting glucose, triglycerides, and TNF-alpha decreased. Only the orlistat group, which was more insulin resistant at baseline, showed a significant reduction in blood glucose after oral glucose load, in addition to increased insulin sensitivity.. This study's findings indicate that a weight loss greater than 5% is associated with improved inflammatory status and decreased insulin resistance, regardless of changes in adiponectin and TNF-a levels. The greatest improvements in insulin sensitivity experienced by the orlistat-treated patients could not be attributed to the use of this drug because of the higher number of insulin-resistant subjects in this group.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; C-Reactive Protein; Chi-Square Distribution; Diet, Reducing; Female; Humans; Hypertension; Insulin Resistance; Lactones; Lipids; Middle Aged; Obesity; Orlistat; Tumor Necrosis Factor-alpha; Waist-Hip Ratio; Weight Loss

Accelerated gastric emptying of solids may play a role in the pathogenesis of obesity. Orlistat, a potent lipase inhibitor, induces fat malabsorption and body weight loss but might accelerate gastric emptying as a result of suppressed CCK release. The aim was to investigate the role of fat restriction and lipase inhibition in CCK release and gastric emptying.. A total of 28 patients (three male (M)/25 female (F); mean (s.d.) BMI 37.4(3.9) kg/m2) entering a randomized, double-blind, placebo-controlled study.. CCK release and gastric emptying by scintigraphy at the start (T0), after 1 month of an energy- and fat-restricted diet and placebo (T1), and after 1 month (T2) and 1 year (T3) of randomization to placebo or 120 mg orlistat three times a day.. One month of dieting and a weight loss of 2.3 kg (2.1% of initial weight) did not affect gastric emptying of liquids and solids. Basal and meal-stimulated CCK levels remained unaltered. Placebo-treated subjects who continued the diet for 1 month demonstrated a borderline significant suppressed CCK secretion and a weight loss of 1.2 kg (1.0%) without an effect on gastric emptying. After 1 year, the CCK secretion recovered to or beyond values at the start. A significantly slower emptying of solids (17.6 (T3) versus 25.9 (T1)%/h) and a weight loss of 10.4 kg (9.9%) was observed. Subjects on 120 mg orlistat lost 2.5 kg (2.5%) after 1 month, and 9.8 kg (9.9%) after 1 year. Basal and postprandial CCK release decreased significantly after the first month of orlistat treatment but normalized after 1 year. Diet and lipase inhibition did not have any influence on gastric emptying.. Energy and fat restriction of 1 month did not alter gastric emptying in the whole group. Continuation of the diet for 1 year resulted in a delayed gastric emptying of solids. Lipase inhibition did not result in a sustained depressed CCK release and the anticipated acceleration of gastric emptying did not occur.

Topics: Anti-Obesity Agents; Cholecystokinin; Diet, Fat-Restricted; Diet, Reducing; Enzyme Inhibitors; Female; Gastric Emptying; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Satiety Response; Weight Loss

Few controlled studies have addressed the issue of effective medical treatment for nonalcoholic fatty liver disease (NAFLD). We herein assessed the effect of orlistat in patients with NAFLD.. We performed a randomized, double-blind, placebo-controlled study on 52 patients with NAFLD diagnosed by ultrasound (US) and confirmed by liver biopsy (40 patients). The patients were randomized to receive either orlistat (120 mg 3 times daily for 6 months) or placebo. All patients participated in an identical behavioral weight loss program. All patients underwent monthly evaluation by abdominal US; liver enzyme levels, lipid profiles, insulin levels, and anthropometric parameters were monitored, and all patients underwent nutritional follow-up evaluation. Twenty-two patients underwent a second liver biopsy examination at the end of the study.. Fifty-two patients were recruited and 44 (mean age, 47.7 y; mean body mass index, 33) completed the study. Serum glucose and insulin levels (P<.03) were significantly higher in the orlistat group, which also presented a higher degree of fibrosis. Body mass index was reduced significantly in each group, with a nonsignificant difference between the groups. Serum alanine transaminase (ALT) levels decreased significantly in both groups, with an almost 2-fold reduction in the orlistat group (48% vs 26.4%). There was a statistically significant reversal of fatty liver by US only in the orlistat group (P<.05).. Orlistat improves serum ALT levels and steatosis on US in NAFLD patients, beyond its effect on weight reduction.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Biopsy, Needle; Body Mass Index; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatty Liver; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lactones; Liver Function Tests; Male; Middle Aged; Orlistat; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler; Weight Loss

Obesity is a major, growing health problem. Observational studies suggest that bariatric surgery is more effective than nonsurgical therapy, but no randomized, controlled trials have confirmed this.. To ascertain whether surgical therapy for obesity achieves better weight loss, health, and quality of life than nonsurgical therapy.. Randomized, controlled trial.. University departments of medicine and surgery and an affiliated private hospital.. 80 adults with mild to moderate obesity (body mass index, 30 kg/m2 to 35 kg/m2) from the general community.. Patients were assigned to a program of very-low-calorie diets, pharmacotherapy, and lifestyle change for 24 months (nonsurgical group) or to placement of a laparoscopic adjustable gastric band (LAP-BAND System, INAMED Health, Santa Barbara, California) (surgical group).. Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years.. At 2 years, the surgical group had greater weight loss, with a mean of 21.6% (95% CI, 19.3% to 23.9%) of initial weight lost and 87.2% (CI, 77.7% to 96.6%) of excess weight lost, while the nonsurgical group had a loss of 5.5% (CI, 3.2% to 7.9%) of initial weight and 21.8% (CI, 11.9% to 31.6%) of excess weight (P < 0.001). The metabolic syndrome was initially present in 15 (38%) patients in each group and was present in 8 (24%) nonsurgical patients and 1 (3%) surgical patient at the completion of the study (P < 0.002). Quality of life improved statistically significantly more in the surgical group (8 of 8 subscores of Short Form-36) than in the nonsurgical group (3 of 8 subscores).. The study included mildly and moderately obese participants, was not powered for comparison of adverse events, and examined outcomes only for 24 months.. Surgical treatment using laparoscopic adjustable gastric banding was statistically significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program.

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Body Mass Index; Caloric Restriction; Diet, Reducing; Exercise Therapy; Female; Gastroplasty; Humans; Lactones; Laparoscopy; Male; Middle Aged; Obesity; Orlistat; Prospective Studies; Quality of Life; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD.. To evaluate a multifactorial intervention in the treatment of NAFLD.. A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study.. At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects.. Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

Topics: Anti-Obesity Agents; Atorvastatin; Diet, Fat-Restricted; Drug Therapy, Combination; Dyslipidemias; Fatty Liver; Female; Fenofibrate; Heptanoic Acids; Humans; Hypolipidemic Agents; Lactones; Male; Metabolic Syndrome; Middle Aged; Orlistat; Prevalence; Prospective Studies; Pyrroles; Risk Factors; Treatment Outcome; Ultrasonography; Weight Loss

To investigate the effects of a pharmacotherapy (orlistat) plus lifestyle management (OLM) intervention on weight loss in Mexican American women with and without metabolic syndrome (MS).. One hundred and seven female participants aged 21-65 years and of Mexican origin were randomized to either OLM or a wait-list control group (WLC) for one year. The lifestyle interventions were tailored to exhibit features of the Mexican culture. Within each group, subjects with MS were compared to those without MS to assess whether its presence mitigates weight loss. Risk factors for MS also were assessed.. Participants with MS in the OLM group experienced significant decreases in weight and body mass index (BMI) as compared to participants without MS. Participants with MS in the OLM group and who completed the study lost 9.3+/-7.5 kg (20.5+/-16.5 lb) as compared to participants with MS in the WLC group, who only lost 0.2+/-3.1 kg (0.4+/-6.8 lb). Further, participants with MS in the OLM group who completed the study experienced a 3.1+/-3.9 kg/m2 decrease in BMI whereas participants with MS in the WLC group only experienced a 0.1+/-1.2 kg/m2 decrease in BMI. No changes in other MS risk factors were significant.. Patients with MS experienced significant weight loss and decreases in BMI as a result of a lifestyle and pharmacotherapy intervention.

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Exercise; Female; Humans; Lactones; Life Style; Metabolic Syndrome; Mexican Americans; Middle Aged; Obesity; Orlistat; Overweight; Risk Factors; Weight Loss

Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss.. To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals.. A multicenter, 16 week, randomized, double-blind, placebo-controlled study was conducted in 391 overweight subjects at 20 US centers. The main outcome measure was change in weight from baseline to week 16; secondary measures included changes in body mass index, waist circumference, blood pressure, and fasting lipoprotein and glucose levels.. Subjects in both groups lost weight over the treatment period; however, orlistat-treated subjects lost significantly more weight than placebo-treated subjects beyond 2 weeks of treatment. Weight loss from baseline to week 16 was significantly greater in participants receiving orlistat versus those receiving placebo (3.05 vs 1.90 kg; p < 0.001, intent-to-treat analysis). Orlistat-treated subjects who completed 16 weeks of treatment lost 4.8 +/- 0.35% (mean +/- SE) of baseline weight compared with 3.1 +/- 0.38% for the placebo group (p < 0.001). Orlistat-treated subjects, compared with those receiving placebo, also demonstrated a greater relative reduction in total (-4.4% vs 0.0%; p = 0.004) and low-density lipoprotein cholesterol (-7.2% vs -0.6%; p = 0.005) and both diastolic (-3.9% vs -0.5%; p = 0.001) and systolic blood pressure (-4.7% vs -1.8%; p = 0.004). Both groups showed a similar safety profile; gastrointestinal events were significantly more common in the orlistat-treated subjects.. The use of orlistat 60 mg by mildly to moderately overweight individuals produced significant weight loss in conjunction with a reduced calorie diet and self-instructional materials. This amount of weight loss was associated with improvements in several weight-related risk factors. Orlistat 60 mg may be a useful adjunct to lifestyle measures and has the potential to contribute significantly to weight and risk factor improvement for overweight individuals.

Topics: Adult; Body Mass Index; Body Weight; Diet, Reducing; Double-Blind Method; Female; Humans; Lactones; Life Style; Male; Middle Aged; Orlistat; Overweight; Time Factors; Weight Loss

There is a significant need for an obesity treatment model suitable for the primary care environment. We examined the effectiveness of a brief counselling intervention alone, in combination with orlistat, and drug-alone in a 12-month randomized-clinical trial at a medical school obesity centre.. Participants (N = 250) with body mass index (BMI) >or=27 were randomized. Changes in body weight, lipids, blood pressure and serum glucose were examined. Drug adherence and attendance were also evaluated.. Completers analysis was conducted on 136 participants with data at baseline, 6 and 12 months and intention-to-treat analyses (ITT) for the total sample. Amongst completers, participants in the drug only (P = 0.012) and drug + brief counselling (P = 0.001) groups lost more weight (mean +/- SD: -3.8 +/- 5.8 kg and -4.8 +/- 4.4 kg, respectively) than participants in the brief counselling only group at 6 months (-1.7 +/- 3.3 kg), but there were no significant group differences at 12 months. ITT model results were similar to completers at 6 months and remained significant at 12 months, but the weight losses were more modest (<3 kg) for both groups receiving orlistat. For brief counselling alone, participants gained weight (1.7 +/- 4.2 kg). Cardiovascular disease (CVD) parameter changes were negligible.. Pharmacotherapy alone or combined with brief counselling resulted in modest weight losses that had minimal impact on cardiovascular parameters, but were greater than brief counselling alone. Whilst brief interventions and primary pharmacotherapy have been suggested as viable treatments for implementation in primary care settings, our study suggests that such minimal interventions provide minimal benefits.

Topics: Adult; Anti-Obesity Agents; Cardiovascular Diseases; Counseling; Humans; Lactones; Life Style; Middle Aged; Obesity; Orlistat; Patient Compliance; Patient Dropouts; Primary Health Care; Risk Factors; Treatment Outcome; Weight Loss

The aim of this study was to investigate effect of loss weight on P wave dispersion in obese subjects.. After a 12-week weight loss program (diet and medical therapy), a total of 30 (24 women and six men) obese subjects who had lost at least 10% of their original weight were included in the present study. All subjects underwent a routine standard 12-lead surface electrocardiogram. Electrocardiograms were transferred to a personal computer by a scanner and then magnified 400 times by Adobe Photoshop software (Adobe Systems, Mountain View, CA). P wave dispersion, which is also defined as the difference between the maximum P wave duration and the minimum P wave duration, was also calculated.. After a 12-week weight loss program, BMI (p < 0.001), maximum P wave duration (p < 0.001), and P wave dispersion (p < 0.001) significantly decreased. The mean percentage of weight loss was 13% (10% to 20.3%). The decrease in the level of P wave dispersion (21 +/- 10 and 7 +/- 12 ms, p < 0.002) was more prominent in Group II (>or=12% loss of their original weight) than Group I (<12% loss of their original weight) after the weight loss program. A statistically significant correlation between decrease in the level of P wave dispersion and percentage of weight loss was found (r = 0.624, p < 0.001).. Substantial weight loss in obese subjects is associated with a decrease of P wave duration and dispersion. Therefore, these observations suggest that substantial weight loss is associated with improvement in atrial repolarization abnormalities in obese subjects.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Triglycerides; 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 objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.

Topics: Adult; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Enzyme Inhibitors; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Lipoproteins; Metformin; Orlistat; Polycystic Ovary Syndrome; Testosterone; Weight Loss; White People

We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4+/-0.5 kg and -9.8+/-0.5 kg (OEWL), -8.3+/-0.8 kg and -5.7+/-0.9 kg (OWL), -8.9+/-1.2 kg and -7.4+/-1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 % (OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2+/-7.2 % (OEWL), -27.8+/-4.8 % (OWL) and -39.3+/-4.3 % (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.

Topics: Adult; Anti-Obesity Agents; Combined Modality Therapy; Exercise Therapy; Female; Humans; Lactones; Leptin; Obesity; Orlistat; Treatment Outcome; Weight Loss

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index (BMI) matched controls. The orlistat group had greater changes in BMI, % body fat (% BF), waist circumference, and insulin resistance, hs-CRP, leptin and adiponectin levels after one year on the program than the controls. After adjusting for % BF and waist circumference, change of serum leptin and adiponectin levels remained significantly different. It was found that orlistat could effectively manage obesity related co-morbidities, especially insulin resistance and atherosclerosis risk. It decreases leptin and increases adiponectin independent of % BF and waist circumference. Therefore, orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people.

Topics: Adult; Anti-Obesity Agents; Arteriosclerosis; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholesterol; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Lactones; Lipoproteins; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Obesity is the most common health problem in developed countries. Recently, several physicians' organizations have issued recommendations for treating obesity to family physicians, including instructions in nutrition, physical activity and medications. The aim of this study was to examine if effective weight-reducing treatment can be given by a family physician. It compares regular treatment with intensive treatment that include close follow-up and orlistat treatment.. The study was conducted in three primary care clinics. 225 patients were divided into three groups according to their choice. Group A received a personal diet with fortnightly meetings with the family physician and dietitian and orlistat treatment. Group B received a general diet, monthly meetings with the family physician only and orlistat treatment. Group C received a personal diet, monthly meetings with the dietitian only and no drug treatment. The primary endpoint was reduction of at least 5% of the initial weight during the study period.. A greater percentage of patients in group A achieved their weight reduction goals than in other groups (51%, 13% and 9% in groups A, B and C, respectively, p < 0.001). There was a significant reduction in triglycerides in all groups, a significant reduction of low density lipids (LDL) in groups A and B and no significant difference in high density lipids (HDL) in any group.. Significant weight reduction was obtained in a family physician setting. Further research is needed to evaluate if, by providing the family physician with the proper tools, similar success can be achieved in more clinics.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Continuity of Patient Care; Diet, Reducing; Family Practice; Female; Health Services Research; Humans; Israel; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Patient Care Team; Primary Health Care; Treatment Outcome; Weight Loss

To assess the effects of orlistat vs. placebo, in combination with a weight management programme, on weight loss and metabolic control in obese patients with Type 2 diabetes.. Patients treated with either metformin alone or metformin in combination with sulphonylurea were randomized to double-blind treatment with orlistat or placebo (120 mg) three times daily, combined with a mildly reduced calorie diet and a weight management programme for 52 weeks. Changes in body weight, anthropometry, glycaemic control and lipid profile were assessed.. After 52 weeks, orlistat-treated patients achieved an almost threefold greater reduction in weight compared with placebo recipients (-5.0% vs. -1.8%; P<0.0001). The decrease in waist circumference was significantly greater with orlistat than placebo (-4.8 cm vs. -2.8 cm; P=0.0022). Orlistat treatment was also associated with significantly greater reductions in haemoglobin A(1c) (-1.1% vs. -0.2%; P<0.0001), fasting plasma glucose (-1.9 mmol/l vs. -0.3 mmol/l; P<0.0001), total cholesterol (-0.2 mmol/l vs. 0.1 mmol/l; P=0.03) and apolipoprotein B (-0.08 g/l vs. 0.01 g/l; P=0.0085) and greater improvements in beta-cell function (P=0.031) and insulin resistance (P=0.001) assessed using the homeostasis model assessment (HOMA). Similar results were obtained for subgroups of patients treated with metformin alone or metformin in combination with sulphonylurea. Orlistat treatment reduced the requirement for anti-diabetic medication more than placebo.. Orlistat, in combination with a reduced calorie diet and a weight management programme, promotes weight loss and clinically relevant improvements in glycaemic control and other cardiovascular risk factors in obese patients with Type 2 diabetes.

Topics: Adult; Aged; Anthropometry; Anti-Obesity Agents; Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lactones; Male; Metformin; Middle Aged; Obesity; Orlistat; Weight Loss

Cognitive behavioral therapy (CBT) has efficacy for binge eating disorder (BED) but not obesity. No controlled studies have tested whether adding obesity medication to CBT facilitates weight loss. We performed a randomized, placebo-controlled study of orlistat administered with guided self-help CBT (CBTgsh).. Fifty obese BED patients were randomly assigned to 12-week treatments of either orlistat plus CBTgsh (120 mg three times a day [t.i.d.]) or placebo plus CBTgsh and were followed in double-blind fashion for 3 months after treatment.. Seventy-eight percent of patients completed treatments without differential dropout between orlistat+CBTgsh and placebo+CBTgsh. Intent-to-treat remission rates (zero binges for past 28 days on Eating Disorder Examination Interview) were significantly higher for orlistat+CBTgsh than placebo+CBTgsh (64% versus 36%) at posttreatment but not at 3-month follow-up (52% in both). Intent-to-treat rates for achieving 5% weight loss were significantly higher for orlistat+CBTgsh than placebo+CBTgsh at posttreatment (36% versus 8%) and 3-month follow-up (32% versus 8%). Significant and comparable improvements in eating disorder psychopathology and psychological distress occurred in both treatments.. The addition of orlistat to CBTgsh was associated with greater weight loss than the addition of placebo to CBTgsh. Clinical improvements were generally maintained at 3-month follow-up after treatment discontinuation.

Topics: Adult; Anti-Obesity Agents; Bulimia; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Orlistat; Psychiatric Status Rating Scales; Treatment Outcome; Weight Loss

To study effects of body mass loss due to orlistat on carbohydrate and lipid metabolism, insulin resistance, 24-h profile of arterial pressure (AP), left ventricular myocardial hypertrophy, brain perfusion in patients with metabolic syndrome (MS).. Thirty middle-aged patients with MS entered the trial. They received orlistat in a dose 120 mg twice a day for 24 weeks. Before and after the treatment the patients' carbohydrate and lipid metabolism, insulin resistance were studied, 24-h monitoring of arterial pressure, echo-cardiography were made. Brain perfusion was studied with single-photon emission computed tomography in 18 patients. Results. All the patients lost much weight. This was accompanied with improved indices of AP profile, metabolism of carbohydrates and lipids, insulin resistance, left ventricular hypertrophy, brain perfusion. Conclusion. Orlistat treatment weakens basic factors of cardiovascular risk.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Cardiovascular Diseases; Cerebral Angiography; Female; Humans; Insulin; Insulin Resistance; Lactones; Lipid Metabolism; Lipids; Male; Metabolic Syndrome; Orlistat; Risk Factors; Weight Loss

The prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weight reduction, and pharmacological treatment has not been extensively studied.. To determine the efficacy and safety of orlistat in weight management of adolescents.. Multicenter, 54-week (August 2000-October 2002), randomized, double-blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI] >or=2 units above the 95th percentile) at 32 centers in the United States and Canada.. A 120-mg dose of orlistat (n = 357) or placebo (n = 182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy.. Change in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge.. There was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5% and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (-1.33 cm vs +0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group.. In combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group.

Topics: Adolescent; Anti-Obesity Agents; Behavior Therapy; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Double-Blind Method; Enzyme Inhibitors; Exercise; Female; Humans; Insulin; Lactones; Lipase; Lipid Metabolism; Male; Obesity; Orlistat; Weight Loss

The anti-obesity drug orlistat promotes weight loss and improves obesity-related risk factors, but its effect on oxidative stress is not clear yet. Orlistat reduces dietary fat absorption, which may have effects on fat soluble vitamins especially the antioxidant vitamins A and E. The aim of this study was to determine and compare the effects of weight loss achieved by orlistat therapy and a combination of orlistat with aerobic exercise training on lipid peroxidation and antioxidative defense in obese subjects. Total of 24 obese subjects were randomly assigned to receive 12-week treatment with hypocaloric diet-orlistat (120 mg three times daily) (DO group) or diet-orlistat-exercise (DOE group). Serum levels of malondialdehyde (MDA), a marker for lipid peroxidation, and vitamins A and E were measured by high performance liquid chromatography at baseline and at the end of the treatment. Body weight and fat mass were significantly reduced in the two groups (p < 0.001). In the DO group, the MDA levels remained unchanged (p = 0.59), while vitamins A (p < 0.01) and E (p < 0.001) were significantly decreased. In contrast, the subjects treated with DOE exhibited marked decreases in MDA (p = 0.002) and a small but significant decrease in vitamins A (p = 0.003) and E (p = 0.003). Thus, orlistat therapy alone caused a significant reduction in antioxidative capacity without affecting oxidative stress, whereas orlistat in combination with exercise training provided a significant decrease in MDA levels. The beneficial effect of aerobic exercise as an adjunct to the orlistat therapy is of importance with regard to the obesity-associated risk factors.

Topics: Adult; Anti-Obesity Agents; Antioxidants; Body Composition; Body Weight; Exercise; Female; Humans; Lactones; Lipid Peroxidation; Male; Malondialdehyde; Obesity; Orlistat; Oxidative Stress; Vitamin A; Vitamin E; Weight Loss

To compare the use of meal replacements or medication during weight maintenance subsequent to weight loss using a very low-energy diet (VLED) in overweight or obese adults.. Participants followed a liquid VLED of 2177 kJ for 12 weeks followed by 4 weeks of re-orientation to solid foods. Participants were randomized at week 16 to receive either meal replacements or Orlistat both combined with a structured meal plan containing an energy value calculated to maintain weight loss.. Sixty-four women (age = 49.9 +/- 10 y, weight = 101.6 +/- 17.1 kg, height = 164.9 +/- 6.0 cm, BMI = 36.7 +/- 5.4 kg/m(2)) and 28 men (age = 53.7 +/- 9.6 y, weight = 121.8 +/- 16.0 kg, height = 178.7 +/- 5.6 cm, BMI = 37.8 +/- 4.9 kg/m(2)) completed a 1 year weight management program. Behavioral weight management clinics included topics on lifestyle, physical activity (PA), and nutrition. Participants met for 90 min weekly for 26 weeks, and then biweekly for the remaining 26 weeks.. Minutes of PA, fruits and vegetables (FV), and pedometer steps were recorded on a daily basis and reported at each group meeting. Body weight was obtained at each group meeting.. During VLED, the MR group decreased body weight by 22.8 +/- 6.1 kg and the Orlistat group decreased body weight by 22.3 +/- 6.1 kg. During weight maintenance, there was no significant group by time interaction for body weight, PA, FV consumption, or pedometer steps. At week 16, the meal replacement group had a body weight of 85.4 +/- 14.3 kg that increased to 88.1 +/- 16.5 kg at 52 weeks (p < 0.05). At week 16, the Orlistat group had a body weight of 85.7 +/- 17.9 kg that increased to 88.5 +/- 20.3 kg at 52 weeks (p < 0.05).. Subsequent to weight loss from a VLED, meal replacements and Orlistat treatments were both effective in maintaining weight significantly below baseline levels over a 52 week period of time. Meal replacements may be a viable alternative strategy to medications for weight maintenance.

Topics: Adult; Aged; Anthropometry; Anti-Obesity Agents; Body Composition; Counseling; Cross-Over Studies; Diet, Reducing; Exercise; Female; Food, Formulated; Health Promotion; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Gain; Weight Loss

To determine the effect of two different levels of energy deficit on weight loss in obese patients treated with orlistat.. Patients (n=430) were randomized in a 1-year, multicentre, open-label, parallel group study conducted at 23 hospital centres and university medical departments worldwide. Obese outpatients (body mass index 30--43 kg/m(2)) aged 18--70 years with a body weight of >or=90 kg and a waist circumference of >or=88 cm (women) or >or=102 cm (men) were treated with orlistat 120 mg three times daily plus a diet that provided an energy deficit of either 500 or 1,000 kcal/day for 1 year. Orlistat treatment was discontinued in patients who did not achieve >or=5% weight loss after assessment at 3 and 6 months. The primary outcome measure was change in body weight from baseline at week 52.. Reported mean difference in energy intake between the two groups (500-1,000 kcal/day deficit) at weeks 24 and 52 was actually 111 and 95 kcal/day respectively. Of the 430 patients involved in the study, 295 achieved >or=5% weight loss at both 3 and 6 months. In this population, at week 52, weight loss from baseline was similar for patients randomized to either the 500 or the 1,000 kcal/day deficit diet (-11.4 kg vs. -11.8 kg, respectively; p=0.778). After 12 months of treatment with orlistat, 84% (n=118/141) and 85% (n=131/154) of patients in the 500 and 1,000 kcal/day deficit groups, respectively, achieved >or=5% weight loss, and 50% (n=70/141) and 53% (n=82/154) of patients, respectively, achieved >or=10% weight loss. Patients in both the diet treatment groups showed similar significant improvements in blood pressure, lipid levels and waist circumference at week 52.. Treatment with orlistat was associated with a clinically beneficial weight loss, irrespective of the prescribed dietary energy restriction (-500 or -1000 kcal/day). Patients who achieved >or=5% weight loss at 3 months achieved long-term, clinically beneficial weight loss with orlistat plus either diet. Therefore, identifying patients who lose at least 5% weight after 3 months and who maintain this weight loss up to 6 months is a valuable treatment algorithm to select patients who will benefit most from orlistat treatment in combination with diet.

Topics: Adolescent; Adult; Aged; Anthropometry; Anti-Obesity Agents; Body Weight; Cardiovascular Diseases; Combined Modality Therapy; Diet, Reducing; Energy Intake; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Patient Compliance; Risk Factors; Treatment Outcome; Weight Loss

Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder.. Eighty-nine patients with clinically diagnosed binge eating disorder and a BMI > or = 30 kg/m2 were randomized in double-blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced-calorie diet.. After 24 weeks, the mean weight loss from baseline for orlistat-treated patients was significantly greater than for patients receiving placebo (-7.4% vs. -2.3%; p = 0.0001) (intent-to-treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011).. Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.

Topics: Anthropometry; Anti-Obesity Agents; Anxiety; Bulimia; Depression; Double-Blind Method; Humans; Lactones; Obesity; Orlistat; Placebos; Weight Loss

Insulin resistance is related to accelerated atherosclerosis, whereas weight loss is associated with the increasing insulin sensitivity, the improvement of functional and the morphological parameters of arterial circulation, and the reduction of cardiovascular morbidity and mortality. The aim of our study was to evaluate the influence of orlistat treatment on serum insulin level and functional and morphologic parameters of peripheral arterial circulation.. We conducted a prospective, randomized, double - blind, placebo - controlled study. Thirty patients with body mass index over 30 kg/m2 normotensive, nonsmokers, without clinically manifested cardiovascular disease or diabetes were randomly assigned either orlistat (120 mg, 3 times daily; n = 20) or placebo (n = 10) in a double - blind manner. All of the patients were on individually calculated hypocaloric diet. The follow-up period was 24 weeks. Arterial pressure, fasting serum glucose and insulin level, triglycerides, total cholesterol and low density lipoprotein-cholesterol were determined at the beginning, following 3 and 6 months. Also, the intima - media thickness of right superficial femoral artery and the mean blood flow velocity were determined with ultrasonography.. Inside the period of 3 and 6 months, there were the greater reductions of body mass index, arterial pressure, fasting glucose and insulin level, total cholesterol, low density lipoproteins, as well as the greater reductions of mean velocity blood flow and peripheral pulse pressure in the orlistat group vs the placebo group (p < 0.01). Greater reductions in the waist circumference and intima - media thickness were registered following 6 months in the orlistat vs the placebo group (p < 0.01).. In the group of obese patients orlistat therapy reduced risk factors, serum insulin level and improved early arterial functional changes as assessed with the reductions of the mean velocity blood flow and peripheral pulse pressure following 3 months. The regression of morphological changes, as assessed with the reduction in intima - media thickness, was feasible over the six - month period.

Topics: Adult; Anti-Obesity Agents; Blood Flow Velocity; Blood Pressure; Double-Blind Method; Female; Femoral Artery; Humans; Insulin; Lactones; Leg; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks' treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes.. A total of 249 Chinese patients (body mass index 25-40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n=124) or orlistat 120 mg (n=125) three times daily; all patients followed a mildly reduced-calorie diet. Patients had HbA1c 6.5-8.5% (mean 7.3%) and had never received any glucose-lowering medication.. Orlistat-treated patients achieved significantly greater weight loss at the study end than placebo-treated patients (-5.4 vs. -2.4 kg; P<0.0001). More orlistat than placebo patients lost>or=5% (60.5 vs. 26.8%; P<0.0001) and >or=10% of their body weight (20.2 vs. 4.9%; P=0.0002). A significantly greater decrease in HbA(1c) from baseline was obtained with orlistat than placebo (-1.0 vs. -0.6%; P=0.0008). Orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P=0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P<0.0001) than placebo recipients. Also, more orlistat- than placebo-treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P=0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference.. In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Glycated Hemoglobin; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Prospective Studies; Weight Loss

Dietary fat has been reported to influence insulin sensitivity.. The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity.. Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss.. The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group.. Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Diet, Reducing; Dietary Fats; Fatty Acids; Female; Humans; Insulin Resistance; Lactones; Middle Aged; Obesity; Orlistat; Weight Loss

Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O).. Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis.. Weight loss resulted in substantial improvement (P < 0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4 mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = -0.41; P < 0.01) but not with weight loss per se.. At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.

Topics: Adipose Tissue; Blood Glucose; Body Composition; Body Mass Index; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Glucose; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Obesity; Orlistat; Placebos; Time Factors; Weight Loss

We examined the effects of weight loss induced by diet-orlistat (DO) and diet-orlistat combined with exercise (DOE) on maximal work rate production (Wmax) capacity in obese patients. Total of 24 obese patients were involved in this study. Twelve of them were subjected to DO therapy only and the remaining 12 patients participated in a regular aerobic exercise-training program in addition to DO therapy (DOE). Each patient performed two incremental ramp exercise tests up to exhaustion using an electromagnetically-braked cycle ergometer: one at the onset and one at the end of the 4th week. DOE therapy caused a significant decrease in total body weight: 101.5+/-17.4 kg (basal) vs 96.3+/-17.3 kg (4 wk) associated with a significant decrease in body fat mass: 45.0+/-10.5 kg (basal) vs 40.9+/-9.8 kg (4 wk). DO therapy also resulted in a significant decrease of total body weight 94.9+/-14.9 kg (basal) vs 91.6+/-13.5 kg (4 wk) associated with small but significant decreases in body fat mass: 37.7+/-5.6 kg (basal) to 36.0+/-6.2 kg (4 wk). Weight reduction achieved during DO therapy was not associated with increased Wmax capacity: 106+/-32 W (basal) vs 106+/-33 W (4 wk), while DOE therapy resulted in a markedly increased Wmax capacity: 109+/-39 W (basal) vs 138+/-30 W (4 wk). DO therapy combined with aerobic exercise training resulted in a significant reduction of fat mass tissue and markedly improved the aerobic fitness and Wmax capacities of obese patients. Considering this improvement within such a short period, physicians should consider applying an aerobic exercise-training program to sedentary obese patients for improving their physical fitness and thereby reduce the negative outcomes of obesity.

Topics: Adolescent; Adult; Anaerobic Threshold; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Exercise; Exercise Therapy; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Physical Fitness; Weight Loss

Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction.. To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation.. Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months.. One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat.. One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.

Topics: Adult; Anti-Obesity Agents; Body Weight; Cholecystokinin; Female; Gallbladder; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients.. A total of 29 type 2 diabetic patients, who were not taking insulin or alpha-glucosidase inhibitors, were enrolled in the study. On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules, followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose.. All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides.. The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug.

Topics: Adult; Aged; Anti-Obesity Agents; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Lactones; Male; Middle Aged; Obesity; Orlistat; Peptide Fragments; Protein Precursors; Single-Blind Method; Weight Loss

Orlistat reduces energy uptake by the impairment of fat digestion and some evidence indicates it also lowers plasma cholesterol.. To examine total, low-density lipoprotein- and high-density lipoprotein cholesterol during a weight reducing regimen, and assess the effect of orlistat in lowering cholesterol levels independent of its weight reducing efficacy.. A total of 448 patients with elevated cholesterol according to cardiovascular risk factors entered a 2 week single-blind run-in period on a hypocaloric diet. Of 384 patients were subsequently assigned double-blind treatment with orlistat (3 x 120 mg/day) or placebo for 6 months in conjunction with the hypocaloric diet.. Weight loss in the orlistat group was 7.4 kg vs. 4.9 kg with placebo. Total and low-density lipoprotein cholesterol decreased by 25-30 mg/dL vs. 10-15 mg/dL with placebo. Reduction of cholesterol with orlistat was significantly greater than anticipated from weight loss alone. In patients with cardiovascular risk factors entering the study with lower cholesterol values orlistat was also superior to placebo. On the contrary, reduction of cholesterol concentrations never exceeded 20%.. Orlistat has a cholesterol lowering efficacy independent of its weight reducing effect. Because of the limited therapeutic effectiveness, patients at high cardiovascular risk should receive rather early additional cholesterol lowering medication during weight loss programmes.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Cholesterol; Cholesterol, LDL; Diet, Reducing; Double-Blind Method; Female; Humans; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Weight Loss

Treatment options for non-alcoholic steatohepatitis (NASH) are limited. Weight loss remains the most recommended therapy. Orlistat is an effective adjunct to dietary weight loss therapy.. To evaluate the efficacy of orlistat, given for 6 months to patients with obesity and biopsy confirmed NASH.. Ten obese patients with biopsy proven NASH were enrolled. Orlistat was given with meals for 6 months. Body Mass Index (BMI), liver enzymes, haemoglobin A1c, fasting lipids and glucose were assessed at baseline and at completion of the study. Paired liver histology was obtained.. Six women and four men were enrolled. The mean weight loss was 22.7 lb and ranged from 0 to 24.3%. The following clinical values significantly improved: mean BMI: 43.4-39.8 (P = 0.007); mean haemoglobin A1c (%): 7.14-5.95 (P = 0.021); mean alanine aminotransferase (ALT) (U/L): 93 -54 (P = 0.009); and mean aspartate aminotransferase (AST) (U/L): 79-48 (P = 0.008). Steatosis improved in six patients, and fibrosis improved in three patients.. Orlistat therapy and dietary counselling were associated with significant decreases in body weight, haemoglobin A1c, ALT and AST. A 10% or greater reduction in weight improved steatosis and fibrosis as well as haemoglobin A1c levels in the majority of patients treated for 6 months. Controlled trials of longer duration are warranted to assess for histopathologic improvement as well as cost-efficacy in comparison to diet and exercise alone.

Topics: Aged; Anti-Obesity Agents; Fatty Liver; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

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

To assess the clinical usefulness of published guidelines for the use of orlistat, by studying whether weight loss >/=2.5 kg during a 4 week dietary lead-in period, and weight losses of >/=5% after 12 weeks and >/=10% after 6 months of drug therapy predict weight loss and risk factor changes after 2 years.. A retrospective analysis of pooled data from 2 multicentre, randomised, placebo-controlled clinical trials with similar design.. Twenty-nine centres throughout Europe.. Two hundred and twenty men and women (BMI 28-43 kg/m(2)) who completed 2 years of treatment.. After a 4 week hypocaloric diet plus placebo, 2 years of treatment with orlistat 120 mg tid, plus a hypocaloric diet for the first year and a weight maintenance diet in year two.. Weight loss and obesity-related risk factor changes.. Weight loss >/=5% body weight after 12 weeks of diet plus orlistat therapy was a good indicator of 2 year weight loss, whereas weight loss of >/=2.5 kg during the 4 week lead-in and >/=10% after 6 months did not add significantly to the prediction of 2 year outcomes. Patients who lost >/=5% of their weight at 12 weeks (n=104, 47.3%) lost significantly more weight after 2 years than others: -11.9% (95% confidence interval (CI) -13.4% to -10.3%) vs -4.7% (-5.7% to -3.7%) (P=0.0001), and had significantly greater reductions in total cholesterol, LDL-cholesterol, triglycerides, glucose, insulin, and blood pressure. Among those who achieved >/=5% weight loss at 12 weeks, the overall health benefits were not significantly greater in patients who went on to lose >/=10% body weight at 6 months compared with those who did not achieve >/=10% weight loss by month 6.. Of the criteria currently suggested for assessing response to orlistat treatment, weight loss of >/=5% at 12 weeks accurately predicts sustained improvements in weight and major risk factors at 2 years, while other suggested criteria are less useful.

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Evidence-Based Medicine; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Practice Guidelines as Topic; Retrospective Studies; Risk Factors; Weight Loss

To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat.. Double-blind, parallel, randomized, placebo-controlled, multicentre study.. Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline.. After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low.. Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.

Topics: Adolescent; Adult; Aged; Anthropometry; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Enzyme Inhibitors; Female; Glycated Hemoglobin; Humans; Insulin; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Weight Loss

Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo.. TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily.. Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001).. Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Body Mass Index; Cardiovascular Diseases; Dinoprost; Double-Blind Method; Female; Follow-Up Studies; Humans; Interleukin-6; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

The objective of this study was to quantify the effectiveness of orlistat plus a reduced calorie diet on decreasing cardiovascular disease risk in obese individuals with elevated low-density lipoprotein (LDL) cholesterol concentrations, and to compare the beneficial effects in patients with hypercholesterolemia only (type IIA) with those in subjects with combined dyslipidemia (type IIB). Hypercholesterolemic patients treated with orlistat lost more weight (mean +/- SEM 9.9 +/- 0.4 vs 6.1 +/- 0.5 kg, p = 0.0001) and had greater decreases in plasma cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), triglycerides (p = 0.06), glucose (p = 0.07), and insulin (p = 0.02) concentrations compared with the diet-only treated patients. The greater degree of weight loss in orlistat-treated subjects was similar irrespective of the form of dyslipidemia, and plasma total and LDL cholesterol and insulin levels decreased to a significantly greater degree (p <0.05) in those patients who received orlistat and who had either type IIA and IIB dyslipidemia. However, triglyceride and insulin concentrations decreased and high-density lipoprotein (HDL) cholesterol increased to a significantly greater degree following orlistat-assisted weight loss in patients with type IIB compared with type IIA subjects, which was associated with a significantly greater decrease in the ratio of LDL/HDL cholesterol. Thus, weight loss in response to a reduced calorie diet in obese hypercholesterolemic patients was associated with a significant decrease in plasma LDL cholesterol levels. The beneficial metabolic effects of weight loss were accentuated in response to orlistat administration, and the improvement was greatest in patients with combined dyslipidemia (type IIB).

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Triglycerides; Weight Loss

To determine the effect of orlistat on weight reduction and the long-term maintenance of this weight loss when associated with a continuous mildly reduced energy diet.. A multicenter, 18-month, double-blind study conducted in 81 hospital centers. Patients were randomized to orlistat 120 mg or placebo three times daily in conjunction with a mildly reduced-energy diet maintained throughout the study.. In total, 696 otherwise healthy, overweight patients aged 18-65 y (BMI >or=28 kg/m(2)) were randomized to treatment with orlistat (n=346) or placebo (n=350).. Body weight, anthropometry, lipid and glycemic control parameters and blood pressure.. After 18 months, patients treated with orlistat lost significantly more body weight compared with placebo (-6.5+/-0.8 vs -3.0+/-0.8%; P=0.0005). After 12 months, 32.9% of orlistat vs 24.5% of placebo patients lost >or=10% of their initial weight (P=0.04). A significantly greater number of patients receiving orlistat treatment maintained this >or=10% weight loss compared to those receiving placebo (28.1 vs 13.8%; P<0.0001). Compared with placebo, orlistat was associated with a greater decrease in fasting blood glucose (-0.86+/-0.12 vs -0.29+/-0.18 mmol/l; P<0.05) and LDL-cholesterol (-13.0+/-1.3 vs -7.0+/-1.3%; P<0.001).. A clinically meaningful reduction in body weight and the maintenance of this weight loss is achievable with orlistat treatment and dietary restriction over a period of 18 months. This weight loss resulted in an improvement in risk factors for coronary heart disease.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Double-Blind Method; Energy Intake; Female; Gastrointestinal Diseases; Humans; Lactones; Long-Term Care; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Treatment Outcome; Weight Loss

Effects of weight loss on vascular function are unknown. We compared, in the face of similar weight loss over 3-6 months, effects of orlistat (120 mg t.i.d., n = 23) and placebo (n = 24) on in vivo endothelial function in a high-risk group of obese (BMI 32.1 +/- 0.4 kg/m(2)) premenopausal nondiabetic women with a history of gestational diabetes.. Forearm blood flow responses to intra-arterial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), body composition, and serum lipids were determined before and after weight loss.. Weight loss averaged 7.3 +/- 0.2 kg (8.3 +/- 0.1%) and 7.4 +/- 0.2 kg (8.2 +/- 0.1%) of initial body weight in the orlistat and placebo groups, respectively. Forearm and body compositions changed similarly in both groups. Responses to ACh increased by 41% to the low dose (5.9 +/- 0.6 vs. 8.3 +/- 0.3 for flow in the experimental/control arm, P < 0.01) and by 33% to the high dose (7.6 +/- 0.8 vs. 10.1 +/- 0.6, P < 0.001) in the orlistat group, but they remained unchanged in the placebo group. The blood flow responses to SNP did not differ significantly between the groups. LDL cholesterol decreased significantly in the orlistat group from 3.5 +/- 0.2 to 3.0 +/- 0.1 mmol/l (P < 0.01) but remained unchanged in the placebo group. Within the orlistat group, the decrease in LDL cholesterol correlated significantly with the improvement in the blood flow response to ACh (r = -0.44, P < 0.05).. Orlistat but not moderate (8%) weight loss per se improves endothelial function in women with previous gestational diabetes. This improvement is associated with a lowering of LDL cholesterol by orlistat.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Cholesterol, LDL; Diabetes, Gestational; Double-Blind Method; Endothelium, Vascular; Female; Forearm; Humans; Lactones; Magnetic Resonance Imaging; Middle Aged; Obesity; Orlistat; Placebos; Pregnancy; Vasodilation; 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

To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients.. A pragmatic randomized, controlled trial.. Hypertension clinic of a university hospital.. Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m(2).. Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group).. Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed.. A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes.. In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients.

Topics: Aged; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Mass Index; Caloric Restriction; Cholesterol; Diabetes Complications; Diabetes Mellitus; Diastole; Fasting; Female; Humans; Hypertension; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Systole; Weight Loss

To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women.. Mexican-American women (N=108), aged 21-65 y, with a body mass index (BMI) > or =27 kg/m(2) were randomized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention (OLM; n=56) or a wait-list control group (WLC; n=52).. A randomized, controlled, open-label 12-month study. Orlistat was dosed at 120 mg, three times per day. The OLM intervention included behavior modification, a low-fat (< or =30% of total daily calories) diet, and moderate physical activity (> or =150 min/week).. Primary outcomes included changes in body weight (kg), BMI, waist circumference, blood pressure, glucose, and lipids.. A total of 72 (37 OLM, 35 WLC) and 66 participants (32 OLM, 34 WLC) completed the 6- and 12-month follow-ups, respectively. Repeated-measures ANOVA demonstrated a significant time x treatment interaction (Wilks' lambda=12.61; P<0.001), indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study (mean percentage weight loss+/-s.e.m.; -8.1%+/-1.2 vs -1.6%+/-0.7 at 6 months and -8.8%+/-1.5 vs -0.2%+/-1.0 at 12 months, respectively). OLM-treated patients also experienced significant reductions in waist circumference, low-density-lipoprotein, and total cholesterol.. This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women, a population with substantial risk for obesity.

Topics: Adult; Aged; Anti-Obesity Agents; Behavior Therapy; Cardiovascular Diseases; Combined Modality Therapy; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Lactones; Life Style; Lipase; Mexican Americans; Middle Aged; Obesity; Orlistat; Risk Factors; Treatment Outcome; Treatment Refusal; Weight Loss

Topics: Adult; Aged; Anti-Obesity Agents; Behavior Therapy; Caloric Restriction; Cooking; Dietary Fats; Female; Follow-Up Studies; Humans; Lactones; Male; Middle Aged; Obesity, Morbid; Orlistat; Weight Loss

The potential effect of orlistat on cardiovascular co-morbidities may have been previously underestimated. This study assesses the efficacy of orlistat therapy for weight loss and cardiovascular risk factor reduction in obese patients with cardiovascular risk. This was a 54-week, double-blind, randomised, placebo-controlled, parallel group study with 531 patients being randomised. Mean weight loss was significantly greater with orlistat than with placebo (5.8% vs 2.3%; p<0.0001). Orlistat was also associated with significantly greater improvements than placebo in diastolic BP (-5.5 vs -3.1 mmHg; p<0.01), systolic blood pressure (-6.0 vs -2.3 mmHg; p<0.01), oral glucose tolerance test (-0.37 vs +0.09 mmol/l; p<0.05), fasting glucose (-0.19 vs +0.06 mmol/l; p<0.05), total cholesterol (-1.31% vs +3.78%; p<0.0001), LDL-cholesterol (-7.09% vs -0.55%; p<0.0001) and waist circumference (-5.99 vs -2.60 cm; p<0.0001). Orlistat was well tolerated. Orlistat weight loss is associated with improvements in cardiovascular co-morbidities, and hence cardiovascular risk.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Obesity Agents; Body Mass Index; Cardiovascular Diseases; Cholesterol; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Risk Factors; United Kingdom; Weight Loss

To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives.. Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed.. Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04).. A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction.

Topics: Anti-Obesity Agents; Antihypertensive Agents; Blood Pressure; Energy Intake; Female; Humans; Hypertension; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

We examined the weight-losing effect of orlistat treatment on insulin sensitivity and cardiovascular risk factors in a group of severely obese young Chinese patients with or without type 2 diabetes mellitus.. Obese patients with diabetes (n = 33) and obese nondiabetic patients (n = 27) were given orlistat, 120 mg 3 times daily, without a concomitant hypocaloric diet for 6 months (body mass index [calculated as weight in kilograms divided by the square of height in meter; kg/m2] range, 27.8-47.4). The efficacy measures were (1) insulin sensitivity indices derived from the homeostasis model assessment and a composite measure of whole-body insulin sensitivity index; (2) glycemic control; (3) cardiovascular risk factors, including anthropometry, blood pressure, lipid profiles, and albuminuria; and (4) body composition determined by dual-energy x-ray absorptiometry.. At baseline, patients with diabetes had lower body mass index and percentage of body fat but higher waist-hip ratios and were more insulin resistant. Orlistat therapy reduced body weight, waist and hip circumferences, percentage of total body fat, blood pressure, fasting plasma glucose and lipid levels, albuminuria, and insulin sensitivity indices in both groups (all, P<.05). Despite less weight reduction, we found a greater percentage of reduction from baseline in glycosylated hemoglobin level (-11.6% vs -3.6%; P<.001), fasting plasma glucose level (-18.2% vs -5.0%; P<.001), and systolic blood pressure (-7.1% vs -3.1%; P =.02) in patients with diabetes. Obese subjects without diabetes had greater improvements in triglyceride levels, albuminuria, and the homeostasis model assessment (all, P<.01).. Short-term orlistat treatment without the use of a hypocaloric diet significantly improved insulin sensitivity and cardiovascular risk profiles in severely obese Chinese patients with or without type 2 diabetes.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; Cardiovascular Diseases; China; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Hong Kong; Humans; Insulin Resistance; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Outpatients; Prospective Studies; Quality of Life; Risk Factors; Time Factors; Weight Loss

The results of the XENDOS study were presented by Professor Lars Sjöström (Gothenburg, Sweden), on August 26, 2002, at the 9th International Congress on Obesity in Sao Paulo, Brazil. XENDOS (XENical in the prevention of Diabetes in Obese Subjects) is a multicentre, randomised, double-blind, placebo-controlled, parallel-group prospective study performed in Sweden over a period of 4 years. The aim of XENDOS was to investigate the use of a weight loss agent (orlistat, Xenical) compared with lifestyle changes for the prevention of type 2 diabetes in obese patients (body mass index > or = 30 kg/m2). Weight loss was greater in the orlistat group (-6.9 kg; n = 1.640) than in the placebo group (-4.1 kg; n = 1.637; p < 0.001). Such a difference in weight reduction was sufficient to significantly reduce the cumulative incidence of type 2 diabetes (6.2% versus 9.0%; p = 0.0032; relative risk reduction of 37.3%). The difference was especially remarkable in obese patients with impaired glucose tolerance (21% of the cohort), with a reduction of conversion to diabetes from 28.8% in the placebo group to 18.8% in the orlistat group (p < 0.005) and a number needed to treat to avoid one event of 11 only. Significant and sustained reductions in cardiovascular risk factors such as arterial blood pressure and lipid levels were also observed in the orlistat group as compared to the placebo group. XENDOS is the first study demonstrating that an antiobesity agent, like orlistat, is able to reduce the progression to diabetes in obese subjects as compared with lifestyle changes alone.

Topics: Adult; Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Lactones; Life Style; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Orlistat; Placebos; Randomized Controlled Trials as Topic; Risk Factors; 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

To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function.. Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet.. Twelve obese patients (11 women, 1 man), age 45.8 +/- 10.5 years, body weight (BW) 99.7 +/- 13.3 kg, BMI 35.3 +/- 2.8 kg/m(2).. At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning.. The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83,p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in S(I) explaining 67% of the variation. First phase insulin response (AIRg)remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later.. In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Composition; C-Peptide; Female; Glucose Tolerance Test; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Placebos; 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

Weight loss seems associated with a decrease in bone mineral density (BMD) as measured by absorptiometry, which may be the result of accuracy errors caused by differences in soft tissue between non-bone and bone pixels. The aim was to study the abdominal fat% and thickness in regions corresponding to non-bone, soft tissue-only and bone pixels for spinal BMD measurements by dual energy X-ray absorptiometry (DXA), and to calculate the theoretical errors in measurement of changes in BMD by DXA as a result of changes in soft tissue heterogeneity with weight loss. Abdominal computed tomography (CT) and DXA scans were performed in 34 obese subjects (42.1+/-10.1 years (mean +/- SD), wt: 102.1+/-12.8 kg and BMI: 36.6+/-3.8 kg m(-2)) before and after weight loss (11.3+/-6.9 kg after 1 year). There were some significant differences in fat% and thickness of soft tissue between abdominal regions corresponding to non-bone and bone pixels, respectively, for spinal BMD measurements by DXA, both before and after weight loss. With weight loss there were some changes in the soft tissue heterogeneity, which caused a minor theoretical error (apparent, but false decrease of 1-2%) of borderline significance for the anterior-posterior (AP) spinal BMD by DXA.

Topics: Absorptiometry, Photon; Adult; Anti-Obesity Agents; Bone Density; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Radiography, Abdominal; Spine; Tomography, X-Ray Computed; Weight Loss

OBJECTIVE; Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients.. This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids. RESULTS; After 1 year, the orlistat group lost significantly more weight (-3.89 +/- 0.3% of baseline body weight, means +/- SE) than the placebo group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA(1c) (-0.62 +/- 0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63 +/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy.

Topics: Anti-Obesity Agents; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lactones; Male; Middle Aged; Obesity; Orlistat; Patient Dropouts; Placebos; Racial Groups; Time Factors; Weight Loss

To study the safety, tolerability, and potential efficacy of orlistat in adolescents with obesity and its comorbid conditions.. We studied 20 adolescents (age, 14.6 +/- 2.0 years; body mass index, 44.1 +/- 12.6 kg/m(2)). Subjects were evaluated before and after taking orlistat (120 mg three times daily) and a multivitamin for 3 months. Subjects were simultaneously enrolled in a 12-week program emphasizing diet, exercise, and strategies for behavior change.. Participants who completed treatment (85%) reported taking 80% of prescribed medication. Adverse effects were generally mild, limited to gastrointestinal effects observed in adults, and decreased with time. Three subjects required additional vitamin D supplementation despite the prescription of a daily multivitamin containing vitamin D. Weight decreased significantly (-4.4 +/- 4.6 kg, p < 0.001; -3.8 +/- 4.1% of initial weight), as did body mass index (-1.9 +/- 2.5 kg/m(2); p < 0.0002). Total cholesterol (-21.3 +/- 24.7 mg/dL; p < 0.001), low-density lipoprotein-cholesterol (-17.3 +/- 15.8 mg/dL; p < 0.0001), fasting insulin (-13.7 +/- 19.0 microU/mL; p < 0.02), and fasting glucose (-15.4 +/- 7.4 mg/dL; p < 0.003) were also significantly lower after orlistat. Insulin sensitivity, assessed by a frequently sampled intravenous glucose-tolerance test, improved significantly (p < 0.02).. We conclude that, in adolescents, short-term treatment with orlistat, in the context of a behavioral program, is well-tolerated and has a side-effect profile similar to that observed in adults, but its true benefit versus conventional therapy remains to be determined in placebo-controlled trials.

Topics: Adolescent; Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, LDL; Dietary Supplements; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Lactones; Male; Obesity; Orlistat; Pilot Projects; Treatment Outcome; Vitamin D; Vitamins; Weight Loss

This study describes the changes in risk factors for coronary heart disease in obese persons with syndrome X after orlistat-assisted weight loss. Data were available for 1,700 patients who completed 52 weeks of weight loss; 128 were defined as having syndrome X by being in the quintile with the highest plasma triglyceride levels (>2.2 mM/L) and the lowest high-density lipoprotein cholesterol (HDL, <1.0 mM/L) concentrations. Initial characteristics of those with syndrome X were similar to the 119 subjects (non-syndrome X) in the lowest quintile of plasma triglyceride (<0.975 mM/L) and highest quintile of HDL cholesterol (>1.5 mM/L). Subjects were placed on a calorie-restricted diet, and randomized to receive orlistat or placebo. Initial values were higher in those with syndrome X for diastolic blood pressure (p = 0.03), plasma insulin (p = 0.0001), triglyceride (p = 0.0001) concentrations, and ratio of low-density lipoprotein cholesterol to HDL cholesterol (p = 0.0001), and were lower for HDL cholesterol (p = 0.001) concentrations. Weight loss was greater in both groups of orlistat-treated patients (p = 0.026); in those with syndrome X, it was associated with a significant reduction in plasma insulin (p = 0.019) and triglyceride (p = 0.0001) concentrations, an increase in HDL cholesterol concentration, and a decrease in low-density lipoprotein/HDL cholesterol ratio (p = 0.0001). There were no significant changes in plasma insulin, triglycerides, or HDL cholesterol concentration in the non-syndrome X group. In conclusion, weight loss attenuates coronary heart disease risk factors in obese persons with syndrome X, and the risk factor reduction is enhanced with administration of orlistat.

Topics: Adult; Anti-Obesity Agents; Cholesterol, HDL; Diet, Reducing; Double-Blind Method; Female; Humans; Insulin; Lactones; Lipase; Male; Microvascular Angina; Middle Aged; Obesity; Orlistat; Risk Factors; Treatment Outcome; Triglycerides; Weight Loss

Orlistat, an intestinal lipase inhibitor, has recently been approved by the US Food and Drug Administration for treatment of obesity. The effects of orlistat on hepatobiliary function have not been previously defined. A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet.. A total of 23 obese (BMI 30-41 kg/m2) subjects were randomized to a double blind t.i.d. treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet (1200-1500 kcal/day). The study was designed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat. Cholesterol saturation, bile composition, and gallbladder motility were measured.. At the end of the treatment period, mean weight loss of 3.8 kg was achieved in the orlistat group (vs 2.3 kg with placebo, p = NS). Total bile acid concentration decreased significantly with placebo (-18.57 +/- 6.99 mmol/L; 95% CI = -32.26 to -4.87), but not with orlistat. Biliary phospholipid concentration decreased significantly with placebo (-4.38 +/- 1.91 mmol/L; 95% CI = -8.13 to -0.64) but not with orlistat. Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups. Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group.. Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids. Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function. We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat.

Topics: Adult; Anti-Obesity Agents; Bile; Bile Acids and Salts; Cholesterol; Double-Blind Method; Energy Intake; Enzyme Inhibitors; Female; Gallbladder; Humans; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients.. A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (-600 kcal/day; < or =30% of calories as fat)), 294 patients were submitted to the hypocaloric diet and randomly assigned to either orlistat 120 mg or placebo three times daily. Patients who completed the double-blind study (n=255) were eligible for participation in a subsequent 24 week open-label orlistat extension phase.. Patients with body mass index (BMI) 27-40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1-6.7 mmol/l).. Efficacy assessments included weight loss, lipid levels, other cardiovascular risk factors and anthropometric parameters. Safety assessments.. Weight loss during run-in was similar in both groups. After randomization, orlistat-treated patients lost significantly more weight than placebo recipients: mean percentage weight loss from start of run-in to week 24 was-6.8% in the orlistat group and -3.8% in the placebo group (P<0.001). Moreover, more patients in the orlistat group than in the placebo group achieved clinically meaningful weight loss of > or =5% (64 vs 39%) or > or =10% (23 vs 13%) at week 24. Treatment with orlistat was associated with significantly greater changes in total cholesterol (-11.9% vs -4.0%; P<0.001) and LDL-C (-17.6 vs -7.6%; P<0.001). For any category of weight loss during the double-blind treatment period, change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients, indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction (P<0.001). Adjunction of orlistat during the extension phase in patients who initially received placebo induced a further decrease in weight, total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo, with the exception of a higher incidence of gastrointestinal events (> or =1 event in 64 vs 38% of patients).. Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Belgium; Cholesterol; Cholesterol, LDL; Diet, Reducing; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypercholesterolemia; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

To determine the effect of orlistat, a new lipase inhibitor, on long-term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity-related risk factors.. This was a 2-year, multicenter, randomized, double-blind, placebo-controlled study. Obese patients (body mass index 28 to 43 kg/m2) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured.. Orlistat-treated patients lost significantly more weight (p<0.001) than placebo-treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p<0.001 for orlistat 120 mg). Several obesity-related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat-treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self-limiting and usually occurred early during treatment.. Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.

Topics: Adult; Anti-Obesity Agents; Cardiovascular System; Diet, Reducing; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Orlistat; Placebos; Risk Factors; Treatment Outcome; Weight Loss

To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity.. Randomized, double-blind, placebo-controlled, multicenter study.. A group of 796 obese patients (body mass index, 30-44 kg/m2), treated with placebo 3 times a day (TID), 60 mg of orlistat TID, or 120 mg of orlistat TID, in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year.. Seventeen primary care centers in the United States.. Changes in body weight and obesity-related disease risk factors.. Patients treated with orlistat lost significantly more weight (7.08 +/- 0.54 and 7.94 +/- 0.57 kg for the 60-mg and 120-mg orlistat groups, respectively) than those treated with placebo (4.14 +/- 0.56 kg) in year 1 (P<.001) and sustained more of this weight loss during year 2 (P<.001). More patients treated with orlistat lost 5% or more of their initial weight in year 1 (48.8% and 50.5% of patients in the 60-mg and 120-mg groups, respectively) compared with placebo (30.7%; P<.001), and approximately 34% of patients in the orlistat groups sustained weight loss of 5% or greater over 2 years compared with 24% in the placebo group (P<.001). Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated, although treatment resulted in a higher incidence of gastrointestinal events.. This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Female; Humans; Insulin; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity, Morbid; Orlistat; Primary Health Care; Risk Factors; Treatment Outcome; United States; Vitamins; Weight Loss

Orlistat is a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, promotes weight loss, and may reduce the risk of developing impaired glucose tolerance and type 2 diabetes in obese subjects.. To test the hypothesis that orlistat combined with dietary intervention improves glucose tolerance status and prevents worsening of diabetes status more effectively than placebo.. We pooled data from 675 obese (body mass index, 30-43 kg/m2) adults at 39 US and European research centers in 3 randomized, double-blind, placebo-controlled multicenter clinical trials. Subjects received placebo plus a low-energy diet during a 4-week lead-in period. On study day 1, the diet was continued, and subjects were randomized to receive placebo 3 times a day (n=316) or treatment with orlistat, 120 mg 3 times a day (n=359), for 104 weeks. A standard 3-hour oral glucose tolerance test was performed on day 1 and at the end of treatment.. The categorical assessment of glucose tolerance status (normal, impaired, diabetic) and changes in status from randomization to end of treatment were the primary efficacy measures. The secondary measures were fasting and postchallenge glucose and insulin levels.. The mean length of follow-up was 582 days. Subjects who were treated with orlistat lost more weight (mean +/- SEM, 6.72 +/- 0.41 kg from initial weight) than subjects who received placebo (3.79+/-0.38 kg; P<.001). A smaller percentage of subjects with impaired glucose tolerance at baseline progressed to diabetic status in the orlistat (3.0%) vs placebo (7.6%) group. Conversely, among subjects with impaired glucose tolerance at baseline, glucose levels normalized in more subjects after orlistat treatment (71.6%) vs placebo (49.1%; P=.04).. The addition of orlistat to a conventional weight loss regimen significantly improved oral glucose tolerance and diminished the rate of progression to the development of impaired glucose tolerance and type 2 diabetes.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus, Type 2; Disease Progression; Double-Blind Method; Female; Humans; Insulin; Lactones; Lipase; Male; Middle Aged; Orlistat; Weight Loss

To examine the effect of orlistat (Xenical) treatment on body composition and resting energy expenditure (REE) during a 2 y weight-reduction programme in obese Finns.. Of initially 96 obese subjects who participated in the weight-reduction programme, those 72 subjects (13 men, 59 women, body mass index (BMI) 35.9 +/- 3.9 kg/m2, age 43.4 +/- 6.0 y, mean +/- s.d.) with the complete set of data for 2 y were included in the study.. After a 4-week lead-in period, subjects were randomized with either orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a mildly hypoenergetic balanced diet for 1 y. This was followed by 1 y double-blind period with the subjects within each treatment group re-assigned to receive orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a weight maintenance diet.. Body composition and REE were measured after an overnight fast by a bioelectrical impedance method and indirect calorimeter, respectively. The measurements were performed at the beginning and at 3, 6, 12 and 24 months.. During the first year, the orlistat-treated group had greater reduction of body weight and fat mass but not of fat-free mass or REE as compared to placebo. During the second year, orlistat treatment was associated with smaller regain of body weight and fat mass with no significant differences in the changes of fat-free mass or REE as compared to placebo.. In addition to better weight loss and maintenance of reduced weight, orlistat treatment is associated with beneficial changes in body composition but with no excess decrease in resting energy expenditure as compared to that achieved during placebo with a dietary therapy alone.

Topics: Adult; Anti-Obesity Agents; Body Composition; Body Constitution; Body Mass Index; Calorimetry, Indirect; Double-Blind Method; Electric Impedance; Energy Metabolism; Enzyme Inhibitors; Female; Finland; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Placebos; Weight Loss

Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.. To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years.. Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.. Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers.. Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks.. Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.. A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels.. Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.

Topics: Adult; Analysis of Variance; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Energy Intake; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Insulin; Lactones; Lipase; Lipids; Male; Obesity; Orlistat; Risk Factors; Weight Loss

Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment.. This multicenter, double-blind, placebo-controlled study was designed to test the hypothesis that orlistat, a gastrointestinal lipase inhibitor, is significantly more effective than a placebo in preventing weight regain.. Obese subjects who lost > or = 8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy were randomly assigned to receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for 1 y in combination with a maintenance diet to help prevent weight regain. Of 1313 recruited subjects [body mass index (in kg/m2): 28-43], 729 subjects lost > or =8% of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase.. After 1 y, subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects (32.8 +/- 4.5% compared with 58.7 +/- 5.8% regain of lost weight; P < 0.001). Moreover, more subjects in the 120-mg orlistat group than in the placebo group regained < or = 25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo (P < 0.001).. The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Cardiovascular Diseases; Cholesterol, HDL; Dietary Fats; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Male; Obesity; Orlistat; Risk Factors; Weight Loss

We undertook a randomised controlled trial to assess the efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period.. 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet.. From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p<0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments.. Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Diet, Reducing; Double-Blind Method; Energy Intake; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Single-Blind Method; Time Factors; Weight Loss

Until recently, obesity did not play a major role in considerations of physicians and public health authorities. The impact of health-threatening overweight was so far considered only as a risk factor for various other serious illnesses, such as hypertension, diabetes mellitus, hyperuricemia, elevated blood lipid levels and of vascular diseases of the heart, the brain and the kidneys. Recently however, obesity has been rated by the WHO as an unique disease, resulting in elevated morbidity and mortality. It is of constantly increasing importance because of the raising number of obese individuals in all industrial countries. In Austria an incidence of 8.5% of the adult population is estimated to be obese with a BMI > 30. Though the established concept for treatment of overweight consists of reduction of the caloric intake by diet, there is an obvious need for drugs making dieting easier acceptable to obese patients for prolonged periods. Orlistat is the first representative of a new class of such drugs, inhibiting intestinal acting lipase thus reducing the intestinal absorption of triglycerides; it contributes, therefore, to a reduced calorie intake. Preliminary results of treatment studies with Orlistat are presented, demonstrating its efficacy in inducing weight loss and improving metabolic parameters with tolerable intestinal side effects. After finalization of international studies, demonstrating efficacy and tolerability, orlistat has been registered in Austria in September 1998.

Topics: Adult; Aged; Austria; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

To study the efficacy of orlistat, as an adjunct to dietary modification, in weight reduction and modification of cardiovascular risk factors in obese patients after 1 year of treatment. A total of 3132 obese patients (body mass index 28-43 kg/m2) were evaluated in an analysis of pooled data from five randomized, double-blind, placebo-controlled trials of orlistat in conjunction with a hypocaloric diet. All studies included a 4-week, single-blind, placebo lead-in period during which patients followed a mildly hypocaloric diet, after which they were randomized to double-blind treatment with orlistat 120 mg three times a day (tid) or placebo for 1 year.. After 1 year, orlistat 120 mg tid produced significantly more weight loss than placebo (9.2% vs 5.8%; P< 0.001). Furthermore, a greater proportion of orlistat-treated patients lost >5% or >10% of their initial body weight compared to placebo (69.6% vs 51.9%; P< 0.001 and 42.1% vs 22.7%; P< 0.001, respectively). Improvements in cardiovascular risk factors were observed during a 4-week placebo lead-in period. However, following randomization, orlistat-treated patients had significantly greater improvements than placebo-treated patients in several lipid parameters including total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and apolipoprotein B. In addition, orlistat had a beneficial effect on oral glucose tolerance tests status, waist circumference and systolic and diastolic blood pressure. Orlistat was well tolerated and had a similar safety profile to placebo.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Diet, Reducing; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Weight Loss

Leptin is likely to be involved in the homeostasis of body weight. Insulin is suggested to regulate both short-term and long-term circulating leptin levels. The present study aims to assess the relation between insulin and leptin levels in obese humans.. Some 53 obese subjects (body mass index 35.1 +/- 3.9 kg m-2 (mean +/- SD)) were prescribed a hypocaloric diet and randomized to either a placebo or the intestinal lipase inhibitor orlistat for 2 years. Serum leptin and insulin levels were determined repeatedly during these 2 years (5 times in the fasting condition and twice after an oral glucose load).. Leptin concentrations appeared to be regulated at a specific level for each individual throughout the weight-loss period. The BMI explained 39.7% of the total variance in leptin levels, the body-fat distribution 17.2%, individual characteristics 30.3%; and the fasting serum insulin concentration 1.0%. After a mean weight loss of 7.7 +/- 4.9 kg, the time-integrated insulin response to an oral glucose load was significantly lower but the leptin response remained unchanged.. The BMI is the main determinant of the circulating leptin concentration in obese humans. Individual characteristics seem to determine the leptin level, given the BMI. In a short-term observational study in obese humans, changes of insulin levels do not appear to be correlated to changes in leptin levels.

Topics: Adult; Biomarkers; Body Mass Index; Diet; Double-Blind Method; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Insulin; Lactones; Leptin; Lipase; Male; Middle Aged; Obesity; Orlistat; Proteins; Single-Blind Method; Weight Loss

To evaluate efficacy and tolerability of the lipase inhibitor Orlistat (Ro 18-0647) in doses of 10, 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30% of calories as fat.. 4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind, placebo-controlled, randomized treatment period.. Five European outpatient clinics specializing in endocrinology and/or the treatment of obesity, one central laboratory.. Of 237 healthy obese subjects meeting the inclusion criteria, 188 showed compliance to the diet during the run-in period and were randomized for the treatment period.. Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group. Secondary efficacy criteria were changes in serum total, HDL- and LDL-cholesterol.. Compared to placebo a mean (+/- s.e.) additional weight loss of 0.63 +/- 0.54 kg with 30 mg a day (P = 0.246), 0.71 +/- 0.55 kg with 180 mg a day (P = 0.190) and 1.75 +/- 0.54 kg with 360 mg a day was seen (P = 0.001) or Orlistat was observed. Overall data indicated dose-dependency. Small decreases were seen in total and LDL-cholesterol (significant in the 180 and 360 mg a day groups) and LDL- to HDL-cholesterol ratio (significant in the 360 mg a day group only). Mild, mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients. No marked laboratory abnormalities were shown, including the lipid-soluble vitamins A, D and E.. Orlistat, in an apparently dose-dependent manner, leads to additional weight loss compared to diet alone and overall, is well tolerated.

Topics: Adult; Cholesterol, HDL; Cholesterol, LDL; Denmark; Diet, Reducing; Dose-Response Relationship, Drug; Double-Blind Method; Female; Germany; Humans; Lactones; Lipase; Male; Middle Aged; Netherlands; Obesity; Orlistat; Sweden; Weight Loss

Orlistat (Ro 18-0647) is an inhibitor of gastric, carboxylester and pancreatic lipase and specifically reduces the absorption of dietary fat due to the inhibition of triglyceride hydrolysis. Orlistat can be used for the treatment of obesity. Of 52 healthy obese patients entering a four-week single-blind run-in period with diet (500 kcal-reduced, containing 30% of calories in the form of fat) and placebo three times a day, 44 patients showed compliance to the diet by reducing their body weight by 0.5-4 kg from screening. These patients were randomized for a 12-week double-blind, parallel group, placebo-controlled treatment period with diet and 50 mg Orlistat or placebo three times a day. Complete data were available for 39 patients, 20 on Orlistat (3 men, 17 women; mean weight 85.5 +/- 12.1 kg; mean body mass index 30.6 +/- 3.7 kg/m2) and 19 on placebo (3 men, 16 women; mean weight 81.9 +/- 7.9 kg; mean body mass index 30.0 +/- 2.6 kg/m2. Total weight loss after randomization was 4.3 +/- 3.4 kg in the Orlistat group and 2.1 +/- 2.8 kg in the placebo group (P = 0.025, analysis of variance with repeated measurements; 95% confidence interval for the weight loss difference 0.2-4.2 kg). Gastrointestinal side effects were seen in the Orlistat group, but in most patients the symptoms were mild or transient. One patient dropped out because of faecal incontinence. No effect was seen on vitamin A levels, but vitamin E levels became lower in the Orlistat group (P < 0.05, paired t test).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Body Mass Index; Chemotherapy, Adjuvant; Double-Blind Method; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Weight Loss

To determine the effectiveness, persistence of use, adverse reactions, interactions of orlistat and liraglutide taken for weight loss by a group of obese patients in Colombia.. A retrospective follow-up study of a cohort of patients with obesity treated with orlistat or liraglutide. Sociodemographic, clinical, and pharmacological variables were identified. The effectiveness for weight loss at 12-16 and 52 weeks, persistence of use, and safety were determined.. A total of 294 patients were followed up. At 12-16 weeks after starting orlistat and liraglutide, weight losses of -1.2kg (p=0.002) and -4.1kg (p<0.001) were observed, respectively, and at 52 weeks, reductions of -1.6kg (p=0.208) and -7.8kg (p<0.001) were observed. A total of 8.8% and 31.3% of patients treated with orlistat and liraglutide, respectively, persisted with treatment 1 year after initiation. A total of 17.3% had adverse drug reactions. Older adults with grade II or III obesity who performed physical activity and those treated with liraglutide were more likely to have lost at least 5% of their body weight at 12-16 weeks.. Orlistat and liraglutide users presented weight loss at 12-16 weeks. However, this effect was greater and sustained with liraglutide, especially when combined with physical activity.

Topics: Aged; Anti-Obesity Agents; Follow-Up Studies; Humans; Lactones; Liraglutide; Obesity; Orlistat; Retrospective Studies; Weight Loss

Topics: Cardiologists; Cardiovascular Diseases; Expert Testimony; Heart Disease Risk Factors; Humans; Obesity; Orlistat; Weight Gain; Weight Loss

The objective of this study was to examine the effects of orlistat use on metabolic control and weight loss in diabetic and nondiabetic patients.. A total of 119 patients with body mass index≥40 kg/m2 and receiving orlistat therapy, who applied to the Endocrinology polyclinic between January 2016 and October 2019, were included. The patients' weight changes and biochemical values (i.e., fasting glucose, HbA1c, ALT, creatinine, and lipid parameters) were evaluated at the drug beginning and the last polyclinic control. The patients were divided into groups, whether they had diabetes or used metformin, and compared.. The mean age of the 119 patients in the study was 45.3±11.5 years. A total of 94.1% of the patients were females and 5.9% were males. A total of 38.7% of the patients had diabetes and 29.4% had prediabetes. When the patients were compared to whether they had diabetes or used metformin, there was a statistically significant difference between the groups according to weight loss. The mean weight change of patients without diabetes and receiving metformin and orlistat was statistically significantly higher than that of patients with diabetes and receiving metformin and orlistat.. It was determined that the weight loss effect of orlistat in obesity was seen in all groups, but this effect decreased in the diabetic group.

Topics: Adult; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Female; Humans; Lactones; Male; Metformin; Middle Aged; Orlistat; Weight Loss

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

The aim was to first investigate the efficacy of a preoperative weight management program centered on orlistat, which is mechanistically similar to gastrointestinal bypass procedures in that it restricts dietary fat absorption, and then assess its impact on the results of one-anastomosis gastric bypass (OAGB).. We retrospectively reviewed the clinical data of consecutive patients aged 20-65 years with a body mass index (BMI) ≥ 42.5 kg/m2 who underwent primary OAGB from 2014 to 2020. Eligible patients who adhered to a 10-14 day orlistat regimen as part of a 4-6-week diet/lifestyle modification plan preceding surgery were stratified into weight reduction (Group 1) and weight gain (Group 2) groups post treatment. The correlation between pre- and postoperative weight loss and perioperative outcomes was assessed.. Of 62 eligible patients, 55 met the inclusion criteria and complied with treatment; 35 (64%) patients in Group 1 lost a median of 2.0 kg, and Group 2 had a median weight gain of 2.9 kg. Group 1 had a significantly higher initial BMI (48.9 kg/m2 vs. 44.6 kg/m2; p = 0.003), more females (54% vs. 25%) and a shorter operation time than Group 2 (107 min vs. 140 min; p = 0.109). There was no difference in the incidence of 30-day complications. Weight loss did not differ between the groups at 24 months.. Effective weight control through an orlistat-containing regimen benefitted two-thirds of patients who underwent OAGB; however, further weight loss was not observed at 2 years post-surgery.

Topics: Female; Gastric Bypass; Humans; Obesity, Morbid; Orlistat; Retrospective Studies; Weight Gain; Weight Loss

Nearly 90% of individuals with type 2 diabetes mellitus (T2DM) are either overweight or obese, placing them at high risk of microvascular and macrovascular complications. The main objective of this study was to assess the use of antiobesity medications and antihyperglycemic agents that produce weight gain among patients with T2DM who qualify for National Institutes of Health guideline-recommended pharmacologic weight loss therapy.. Among adults with T2DM who qualified for antiobesity treatment (N = 2910), only 40 participants (2.2%; 95% CI, 1.5-3.3) were on pharmacologic antiobesity treatment within 30 days of survey interview. The only antiobesity medications identified were liraglutide (n = 34 [1.9%]), phentermine (n = 4 [0.2%]), orlistat (n = 1 [0.1%]), and phentermine/topiramate (n = 1 [0.0%]). Among those who were on antihyperglycemic treatment (n = 2401), 1661 (66%; 95% CI, 63.1-68.8) were on weight-inducing antihyperglycemic agents; however, a downward trend in the use of these agents over time was observed (from 78.4% in 2005-2006 to 53.3% in 2015-2016; P < 0.0005).. This is the first national epidemiologic study evaluating the use of antiobesity medications and weight-inducing antihyperglycemic agents among patients with T2DM who qualify for weight loss therapy. This study documents that patients are not on guideline-directed weight loss therapy. Furthermore, weight loss goals are likely compromised by 66% of individuals being on weight-inducing antihyperglycemic therapy. Use of antiobesity medications could play a significant role in promoting weight loss and potentially lead to a healthier lifestyle, which could reduce microvascular and macrovascular complications. Stronger recommendations in using guideline-directed therapy in obesity complicated by T2DM are necessary.

Topics: Adult; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Liraglutide; Nutrition Surveys; Obesity; Orlistat; Phentermine; Prevalence; Topiramate; United States; Weight Loss

Obesity is a widespread medical problem, for which many drugs have been developed, each with its own limitations. Orlistat, a lipase inhibitor, functions as a fat absorption blocker and is a widely used over-the-counter drug in China. Psyllium husk, in contrast, is a food source rich in dietary fibre and is beneficial for weight loss because it reduces appetite. Here, it was investigated how psyllium husk treatments affect mice with a high-fat diet (HFD)-induced obesity, using obesity-related indices, metabolism indices, and gut microbiota, compared to orlistat treatments. Orlistat had a greater effect on weight loss, whereas psyllium husk had a greater effect at reducing serum and liver cholesterol and triglyceride levels. Treatments had similar effects on controlling the body fat rate, the expression level of farnesoid X receptor, sterol 27-hydroxylase and oxysterol 7-hydroxylase (CYP7B1) in the liver, and the regulation of major bile acids such as cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid in faecal content. However, the expression of CYP7A1 in the liver and the structures of faecal bile acids were different between the two drugs. Furthermore, although they also had similar effects on the gut microbiota at the phylum level, there were differences at the genus level for

Topics: Animals; Anti-Obesity Agents; Bile Acids and Salts; Diet, High-Fat; Hypercholesterolemia; Hyperlipidemias; Liver; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Psyllium; Triglycerides; Weight Loss

Obesity as a chronic, serious, and progressive lifelong disease requires an active approach to treatment. Treatment means necessary adjustment of lifestyle with suitable regular physical activity, including pharmacological or bariatric support. Current pharmacological treatment can be an effective helper in the preparation for the surgical treatment of obesity (bariatric and metabolic operations), and in greater adherence of the patient to the necessary regime changes in life and in preoperative weight reduction. With the lapse of time after surgical treatment, in many cases we indicate the start of pharmacological treatment if the weight increases again. We do not yet know the appropriate types of patients and the exact indications for specific therapeutic modalities - a suitable antiobesity drug or type of bariatric surgery. The best long-term results come from a combination of at least two of these options, along with a lifestyle change. Among modern antiobesity drugs, there are naltrexone-bupropion and liraglutide. Orlistat can be mentioned from older ones.

Topics: Anti-Obesity Agents; Bariatric Surgery; Humans; Obesity; Orlistat; Weight Loss

To compare the effectiveness of weight-management medications used to assist with weight loss in real-world clinical practice in the Veterans Health Administration (VHA).. Retrospective, multicenter, observational cohort study.. National VA Corporate Data Warehouse.. A total of 66,035 VA patients aged 18 years or older with a body mass index of 25 kg/m. The primary outcome was the percentage change in weight from baseline to at least 20 weeks or later (i.e., closest weight to 6 months). Secondary outcomes were difference in the percentage of weight loss at 12 and 36 weeks; changes in blood pressure, hemoglobin A. In the VA population, the effectiveness of four available weight-management medications was similar. Patients receiving phentermine-topiramate had a greater proportion of weight loss after at least 20 weeks compared with those solely enrolled in the VA's MOVE! weight-management program.

Topics: Adult; Aged; Anti-Obesity Agents; Benzazepines; Body Weight; Cohort Studies; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Obesity; Orlistat; Phentermine; Retrospective Studies; Topiramate; United States; United States Department of Veterans Affairs; 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

Topics: Anti-Obesity Agents; Body Weight; Humans; Lactones; Lipids; Obesity; Orlistat; Sample Size; Weight Loss

The prevalence of obesity is surging in an alarming rate all over the world. Pharmaceutical drugs are considered potential adjunctive therapy to lifestyle modification. However, for most, besides being too expensive, their long term usages are hindered by their severe adverse effects. Here we describe the effect of UP601, a standardized blend of extracts from Morus alba, Yerba mate and Magnolia officinalis, in modulating a number of obesity-related phenotypic and biochemical markers in a high-fat high-fructose (HFF)-induced C57BL/6J mouse model of obesity.. Adipogenesis activity of the composition was assessed in 3T3-L1 cells in vitro. Effects of UP601 on body weight and metabolic markers were evaluated. It was administered at oral doses of 300 mg/kg, 450 mg/kg and 600 mg/kg for 7 weeks. Orlistat (40 mg/kg/day) was used as a positive control. Body compositions of mice were assessed using dual energy X-ray absorptiometry (DEXA). Serum biomarkers were measured for liver function and lipid profiling. Relative organ weights were determined. Histopathological analysis was performed for non-alcoholic steatohepatitis (NASH) scoring.. UP601 at 250 μg/ml resulted in 1.8-fold increase in lipolysis. Statistically significant changes in body weight (decreased by 9.1, 19.6 and 25.6% compared to the HFF group at week-7) were observed for mice treated with UP601 at 300, 450 and 600 mg/kg, respectively. Reductions of 9.1, 16.9, and 18.6% in total cholesterol; 45.0, 55.0, 63.6% in triglyceride; 34.8, 37.1 and 41.6% in LDL; 3.2, 21.6 (P = 0.03) and 33.7% (P = 0.005) in serum glucose were observed for UP601 at 300, 450 and 600 mg/kg, respectively. Body fat distribution was found reduced by 31.6 and 17.2% for the 450 mg/kg UP601 and orlistat, respectively, from the DEXA scan analysis. Up to an 89.1% reduction in mesenteric fat deposit was observed for UP601 in relative organ weight. Statistically significant improvements in NASH scores were observed for mice treated with UP601.. UP601, a standardized botanical composition from Morus alba, Yerba mate and Magnolia officinalis could potentially be used for achieving healthy weight loss and maintenance.

Topics: 3T3-L1 Cells; Adipogenesis; Animals; Blood Glucose; Body Fat Distribution; Diet; Disease Models, Animal; Hypoglycemic Agents; Hypolipidemic Agents; Ilex; Lactones; Lipids; Lipolysis; Liver; Magnolia; Mice; Mice, Inbred C57BL; Morus; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phytotherapy; Plant Extracts; Weight Loss

Obesity is a chronic disease universally defined as an excess of adipose tissue resulting in body mass index (BMI) > 30.0 kg/m2. Over the past few years, the concept of prevention has gained increased awareness, thus leading to the development of additional pharmaceutical options for the treatment of obesity since 2012. Treating obesity revolves around an individualized, multi-disciplinary approach with additional focus on a healthy and supportive lifestyle to maintain the weight loss. [Full article available at http://rimed.org/rimedicaljournal-2017-03.asp].

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Bupropion; Drug Combinations; Fructose; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Weight Loss

Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution.

Topics: Animals; Anti-Obesity Agents; Drug Carriers; Lactones; Lipase; Male; Mice; Mice, Inbred ICR; Nanoparticles; Orlistat; Weight Loss

poco se conoce sobre el impacto de orlistat en el sistema leptina. Estudiamos la respuesta de la leptina plasmática y la sensación de saciedad tras dos días de tratamiento con orlistat sin dieta hipocalórica ni pérdida de peso.. reclutamos veinte mujeres obesas en nuestras consultas externas de medicina. Habían recibido restricción dietética y modificación del estilo de vida, pero se habían mantenido obesas con peso corporal estable durante seis meses antes de su inclusión en el estudio.. las pacientes tomaron 120 mg de orlistat 3 veces al día y mantuvieron su dieta habitual. Al inicio y dos días después del tratamiento con orlistat se repitieron el examen físico, la sensación de hambre y la analítica. No hubo diferencias significativas en el consumo de energía de la dieta, el peso corporal y la relación cintura-cadera, así como en glucosa sérica, insulina y péptido C. Solamente las concentraciones de leptina y triglicéridos en suero disminuyeron (p: 0,0001 y 0,01, respectivamente). La disminución de la concentración de leptina en suero se correlacionó positivamente con cambios en la concentración de triglicéridos (p: 0.01, r2: 0,45). La sensación de hambre aumento antes de la cena y se correlacionó negativamente con la disminución de la leptina (p: 0,0001, r2: 0,74) y triglicéridos (p: 0,02, r2: 0.59).. estos datos sugieren que la malabsorción parcial de grasas por el tratamiento con orlistat disminuye rápidamente los niveles plasmáticos de triglicéridos y leptina. Este descenso se asoció con aumento del apetito antes de la ingesta que sigue a la comida principal del día.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Dietary Fats; Female; Humans; Intestinal Absorption; Lactones; Leptin; Orlistat; Satiety Response; Triglycerides; Weight Loss

The recent approval of liraglutide, lorcaserin, naltrexone/bupropion extended-release, and phentermine/topiramate extended-release, brings the number of medications for long-term weight loss to 5 (including orlistat). Indicated for the treatment of patients with overweight (body mass index [BMI] ≥27 kg/m2 with ≥1 weight-related comorbidity) or obesity (BMI ≥30 kg/m2), these medications provide new opportunities to address this burgeoning health problem.

Topics: Anti-Obesity Agents; Benzazepines; Body Mass Index; Bupropion; Guidelines as Topic; Humans; Lactones; Life Style; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Primary Health Care; Risk Factors; Treatment Outcome; 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

Obesity is a chronic metabolic disease that affects an increasing number of people around the world. There have been limited studies evaluating the weight loss effects of orlistat in the Korean population, whose diet is different from that of the Caucasian population. The primary objective of this study was to evaluate the effect of orlistat on the weight and body mass index of obese and overweight Korean patients. The secondary objective was to evaluate the effects of orlistat on risk factors for obesity and metabolic disorders. Obese adult patients with a body mass index greater than 25 kg/m(2) who received 120 mg of orlistat three times daily for 24 weeks were included in this study. Patients were retrospectively evaluated for changes in body weight and body mass index, as well as waist and hip circumference, body fat levels, serum lipid levels, fasting glucose levels, and blood pressure. The evaluation included 63 patients. Treatment with orlistat for 4, 12, or 24 weeks significantly decreased the weight, body mass index, waist circumference, and hip circumference compared to that at the baseline. The average weight loss was 3.0 kg at 12 weeks and 3.6 kg at 24 weeks, which indicated a 3.8 and 4.6 % decrease from initial weight, respectively. The number of patients who lost more than 10 % of their initial body weight was 3 (4.8 %) at 12 weeks and 27 (7.9 %) at 24 weeks. About 27 % of patients reported gastrointestinal-related adverse effects with orlistat, but no serious adverse effects were reported. A retrospective study of overweight and obese Korean patients showed that treatment with orlistat for 24 weeks significantly decreased body weight and body mass index compared to the initial weight.

Topics: Adipose Tissue; Asian People; Blood Glucose; Blood Pressure; Body Mass Index; Fasting; Female; Humans; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Overweight; Risk Factors; Waist-Hip Ratio; Weight Loss

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

Orlistat is used clinically worldwide as anti-obesity drug. It is a chemically synthesized hydrogenated derivative of lipstatin and is an inhibitor of gastric and pancreatic lipases. It has been found to reduce the absorption of dietary fat in the gastrointestinal tract. Modeling and simulation based on pharmacokinetic/pharmacodynamic analysis is becoming increasingly used in the design of clinical trials to assure that the trials are of high quality and are conducted efficiently. We developed a clinical trial simulation model for orlistat based on Phase III clinical study data. This innovative weight loss model includes the relationships between orlistat dose, changes in fecal fat excretion, and weight loss, and also incorporates a dropout function. The model guided the dose-finding strategy and allowed simulation of long-term clinical outcomes of orlistat.

Topics: Anti-Obesity Agents; Body Weight; Clinical Trials, Phase III as Topic; Humans; Lactones; Models, Theoretical; Obesity; Orlistat; Weight Loss

There is no established primary care solution for the rapidly increasing numbers of severely obese people with body mass index (BMI) > 40 kg/m(2).. This programme aimed to generate weight losses of ≥15 kg at 12 months, within routine primary care.. Feasibility study in primary care.. Patients with a BMI ≥40 kg/m(2) commenced a micronutrient-replete 810-833 kcal/day low-energy liquid diet (LELD), delivered in primary care, for a planned 12 weeks or 20 kg weight loss (whichever was the sooner), with structured food reintroduction and then weight-loss maintenance, with optional orlistat to 12 months.. Of 91 patients (74 females) entering the programme (baseline: weight 131 kg, BMI 48 kg/m(2), age 46 years), 58/91(64%) completed the LELD stage, with a mean duration of 14.4 weeks (standard deviation [SD] = 6.0 weeks), and a mean weight loss of 16.9 kg (SD = 6.0 kg). Four patients commenced weight-loss maintenance omitting the food-reintroduction stage. Of the remaining 54, 37(68%) started and completed food reintroduction over a mean duration of 9.3 weeks (SD = 5.7 weeks), with a further mean weight loss of 2.1 kg (SD = 3.7 kg), before starting a long-term low-fat-diet weight-loss maintenance plan. A total of 44/91 (48%) received orlistat at some stage. At 12 months, weight was recorded for 68/91 (75%) patients, with a mean loss of 12.4 kg (SD = 11.4 kg). Of these, 30 (33% of all 91 patients starting the programme) had a documented maintained weight loss of ≥15 kg at 12 months, six (7%) had a 10-15 kg loss, and 11 (12%) had a 5-10 kg loss. The indicative cost of providing this entire programme for wider implementation would be £861 per patient entered, or £2611 per documented 15 kg loss achieved.. A care package within routine primary care for severe obesity, including LELD, food reintroduction, and weight-loss maintenance, was well accepted and achieved a 12-month-maintained weight loss of ≥15 kg for one-third of all patients entering the programme.

Topics: Adult; Anti-Obesity Agents; Diet, Reducing; Feasibility Studies; Feeding Behavior; Feeding Methods; Female; Humans; Lactones; Male; Micronutrients; Middle Aged; Obesity, Morbid; Orlistat; Patient Compliance; Patient Education as Topic; Patient Satisfaction; Treatment Outcome; Weight Loss; Young Adult

Trials of weight-loss drugs indicate some benefits on lipids, blood glucose, or blood pressure levels. Since obesity is associated with increased cardiovascular (CV) medication use and pharmaceutical costs, weight-loss drug use could beneficially impact CV medication use.. We examined the temporal associations between CV drugs use 3 years before and after the initiation of orlistat, a weight-loss drug.. An historical cohort study in the PHARMO pharmacy registry among new users of orlistat, who were in the database at least 3 years before and after such drug initiation. We assessed the prevalence of use of antihypertensive, antidiabetic, and lipid-lowering drugs within a 6-month period before and after orlistat initiation. Slopes and changes in slopes between these two periods were calculated using logistic generalized estimating equations and odds ratios (OR) with 95% confidence intervals (CI) are presented.. A total of 6139 subjects had a prescription of orlistat between January 1992 and May 2009. Mean ± SD age was 46.5 ± 12.5 years, with a majority of female (88.7%). Use of antihypertensive, antidiabetic, and lipid-lowering drugs increased over time, but after start of orlistat the slopes levelled-off. Initiation of orlistat resulted in a significant change in slope for antihypertensive (OR 0.79; 95% CI 0.77-0.81), antidiabetic (0.86; 0.83-0.90), and lipid-lowering drugs (0.84; 0.81-0.88).. Our data suggest a potential cost-effectiveness of orlistat, with a reduction in any cardiovascular comedication use over time. By potentially reducing costs of other medications use, orlistat remains as a unique option for tackling the obesity epidemic.

Topics: Adult; Anti-Obesity Agents; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Cost Savings; Drug Costs; Drug Prescriptions; Epidemics; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Lactones; Logistic Models; Longitudinal Studies; Male; Middle Aged; Netherlands; Obesity; Odds Ratio; Orlistat; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Loss

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS).. We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet.. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group.. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Topics: Adipokines; Adiponectin; Adult; Anti-Obesity Agents; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Polycystic Ovary Syndrome; Resistin; Waist Circumference; Weight Loss; Young Adult

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; Body Mass Index; Holidays; Humans; Lactones; Life Style; Obesity; Orlistat; Seasons; Weight Loss

Sleep related breathing disorders (SRBD) are associated with increased morbidity and mortality and weight loss is recommended to overweight or obese patients with SRBD. However, maintenance of weight loss is difficult to achieve and strategies for weight loss maintenance is needed. Orlistat is a pharmacological agent that reduces the intestinal absorption of fat and may favour long-term weight maintenance.. To examine the change in body weight and dietary intake during a 1-year treatment with orlistat after an initial weight loss in obese subjects with SRBD. Furthermore, to explore the dietary determinants of weight maintenance during treatment with orlistat.. Men and women with SRBD aged 32-62 years (n=63) participated in a 3-month dietary intervention to increase intake of vegetables and fruit. After an initial weight loss of 3.4 kg they achieved a mean body mass index of 34.3±4.7 kg/m2. Subsequently they were treated with orlistat for 1 year. During this year, dietary and behavioural interventions to attain weight loss were provided in the course of 14 group sessions. Dietary intake, energy density and food choices were assessed with a food frequency questionnaire before and after orlistat treatment.. With orlistat, body weight decreased by a mean of 3.5 kg (95% CI 1.5, 5.5). The dietary E% from saturated fat, intake of fatty dairy products and energy density increased after 1 year while intakes of oils, fish and vegetables decreased (all P<0.05). After multivariate adjustments, weight loss was associated with E% protein (R2adj=0.19 [95% CI 0.10, 0.46]), and inversely associated with E% saturated fat (R2adj=0.20 [95% CI 0.12, 0.47]) and fatty dairy products (R2adj=0.23 [95% CI 0.12, 0.49]).. Orlistat induced further weight loss, but dietary compliance declined with time. Increasing dietary protein and restricting saturated fat and fatty dairy products may facilitate weight loss with orlistat.

Topics: Anti-Obesity Agents; Body Weight; Diet; Female; Humans; Lactones; Male; Obesity; Orlistat; Patient Compliance; Sleep Apnea Syndromes; Weight Loss

To assess the efficacy of a specific long-term programme for weight loss maintenance using a new 'on/off' Orlistat approach in obese subjects who previously lost more than 10% of their body weight.. 50 patients were followed up during 4 years; 34 completed the study. Subjects were followed up by physicians trained in obesity management. Anthropometrical, biological and psychological parameters were measured. Insulin sensitivity was evaluated by euglycaemic insulin clamp. Orlistat was given in case of weight relapse more than 2.5%. Subjects could take Orlistat on a voluntary basis for special occasions.. The BMI of completers remained stable (29.5 ± 0.9 vs. 30.6 ± 1.0 kg/m(2)). 73% of completers maintained 10% or more of their weight loss. Subjects from the no-regain group improved most of their parameters while the regain group did not. Insulin sensitivity was negatively linked to body weight during the follow up (p < 0.01, r(2) = 0.20). A negative relationship has been found between extent of the previous weight loss and the evolution of body weight during the 4 years follow-up (p < 0.01, r(2) = 0.26). Orlistat intake showed a body fat lowering effect (p < 0.05).. 73% of subjects maintained more than 10% of their weight loss. Subject with a large weight loss amount are at high risk for weight regain. The Orlistat 'on/off' intake regarding his lowering body fat mass effect seems to be efficient.

Topics: Adipose Tissue; Adult; Anti-Obesity Agents; Body Mass Index; Female; Follow-Up Studies; Humans; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Recurrence; Treatment Outcome; Weight Gain; Weight Loss

Dyslipidemia is frequently found in association with obesity. Obesity-related dyslipidemia is characterized by elevated triglycerides, elevated VLDL, increased apo-B, decreased HDL cholesterol and increased small dense LDL particles. This combination of lipid abnormalities is particularly atherogenic and, along with related comorbidities, explains the increased cardiovascular risk seen in obesity. Weight loss, through diet, medication and/or surgery all result in beneficial effects upon serum lipids. Dietary modification and lifestyle change are essential components in the management of obesity-related dyslipidemia. Many patients, however, require pharmacotherapy to achieve lipid goals.

Topics: Anti-Obesity Agents; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Hypolipidemic Agents; Lactones; Life Style; Niacin; Obesity; Orlistat; Weight Loss

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

Topics: Anti-Obesity Agents; Blood Pressure; Body Mass Index; Humans; Hypertension; Lactones; Orlistat; Weight Loss

Topics: Anti-Obesity Agents; Bariatric Surgery; Behavior Therapy; Body Mass Index; Caloric Restriction; Clinical Trials as Topic; Consensus Development Conferences as Topic; Diet Records; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Exercise; Female; Humans; Lactones; Male; Metabolic Syndrome; Obesity; Orlistat; Physical Exertion; Practice Guidelines as Topic; Time Factors; Waist Circumference; Weight Loss

Topics: Administration, Oral; Adult; Anti-Obesity Agents; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet, Reducing; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucagon-Like Peptide 1; Humans; Injections, Subcutaneous; Lactones; Liraglutide; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Orlistat; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Weight Loss

The present study aims to evaluate the effects of orlistat-assisted weight loss on endothelium-dependent vasodilation by ultrasonography in obese Chinese subjects with hypertension. Thirty obese hypertensive patients (mean age: 46.6 +/- 10.3 yr, male:12) were given 120 mg of orlistat 120 mg three times daily for 12 weeks, without a concomitant hypocaloric diet or anti-hypertensive drugs. Fifteen concurrent blood pressure, age, and gender-matched, nonobese hypertensive patients (mean age: 46.6 +/- 11.3 yr, male:6) served as the control. The height, body weight, waist circumference (WC), and blood pressure were measured and flow-mediated dilation (FMD) and the nitroglycerin-mediated dilation (NMD) of brachial artery was determined by high-resolution ultrasound before and after 12 weeks treatment with orlistat. The baseline parameters were comparable between the two groups, while body mass index (BMI) and WC were greater in the obese group (p < 0.01). Before treatment, the brachial artery diameter was increased by 9.6% following reactive hyperemia in the obese group, significantly lower than that in the control group (13.3%, P < 0.01). Nitroglycerin-mediated dilation was not difference between the two groups. After 12 weeks of orlistat treatment, the brachial artery diameter was increased by 14.2%, and the FMD was significantly improved (P < 0.01), associated with a significant reduction in weight, BMI, WC, and blood pressures. Nitroglycerin-mediated dilation was not significantly affected. On multiple regression analysis, improvement in FMD was determined by change of body weight (Beta = -0.555, P = 0.001), after adjustments for height, heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and WC. Orlistat can effectively reduce body weight and blood pressure and improve endothelium-dependent FMD in obese Chinese hypertensives.

Topics: Adult; Anti-Obesity Agents; China; Endothelium, Vascular; Female; Humans; Hypertension; Lactones; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

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

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

Liposuction can aggravate metabolic complications associated with obesity. It has been shown that the recovery of weight lost through these interventions is associated with body fat redistribution toward the visceral cavity, increasing metabolic risk factors for coronary heart disease such as insulin resistance and high triglyceride levels.. The aim of this study was to evaluate the consequences of liposuction on body mass redistribution and metabolic parameters 6 months after surgery and to evaluate the use of orlistat treatment (tetrahydrolipstatin) in controlling these parameters.. A population of 31 women with a mean body mass index of 26.17+/-3.9 kg/m(2) and undergoing liposuction of more than 1,000 cm(3), was studied. Twelve of them were treated postsurgery with 120 mg of orlistat every 8 hours for the following 6 months. Anthropometric, analytical, and radiological (computed tomography) tests were performed to quantify visceral fat area before surgery and 6 months after surgery.. Despite weight loss after liposuction, visceral fat was not modified. Patients treated with orlistat showed a greater reduction in visceral fat, although not statistically significant. Orlistat use induced a reduction in low-density lipoprotein cholesterol values of 20.0+/-22.5 mg/dL, compared with an increase of 8.46+/-20.1 mg/dL in controls (p=.07).. Visceral fat does not decrease despite weight loss after liposuction. Orlistat use postliposuction might be a useful tool because it shows a tendency to reduce visceral fat and improve blood lipids profile.

Topics: Abdominal Fat; Adult; Anti-Obesity Agents; Body Composition; Body Fat Distribution; Female; Humans; Lactones; Lipectomy; Orlistat; Postoperative Period; 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

Topics: Anti-Obesity Agents; Dose-Response Relationship, Drug; Feeding Behavior; Glucagon-Like Peptide 1; Half-Life; Humans; Lactones; Liraglutide; Obesity; Orlistat; Weight Loss

Orlistat first became available (as 120 mg capsules [Xenical]) around 10 years ago as a prescription-only treatment for obesity. Earlier this year, orlistat 60 mg capsules (alli - GlaxoSmithKline Consumer Healthcare) became available for sale without a prescription to the public in the European Union. Orlistat 60 mg is available in the UK as a Pharmacy (P) medicine and so can be purchased over-the-counter (OTC) from pharmacies. OTC orlistat is promoted as a new weight loss aid, "boosting weight loss by 50%" when added to a reduced calorie, lower-fat diet. Here we review the place of OTC orlistat in tackling obesity.

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

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

Topics: Anti-Obesity Agents; Bridged Bicyclo Compounds, Heterocyclic; Caloric Restriction; Fenfluramine; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; 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

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

Kidney transplantation in obese patients [body mass index (BMI) >30 kg/m(2)] is associated with a poorer outcome, and these patients are therefore often excluded from transplant waiting lists. Conventional weight loss strategies based on a high fibre, low energy diet and exercise are often unsuitable in the chronic kidney disease (CKD) population. A comprehensive multidisciplinary weight management programme comprising a low fat, reduced energy diet, individual exercise prescription and pharmacotherapy with orlistat 120 mg tds, was initiated to determine whether obese patients with CKD could reach an acceptable weight for transplantation.. Thirty-two patients who completed 12 months in the programme were monitored regularly for weight and waist circumference measures as well as exercise performance tests. Twenty-two patients formed a contemporaneous control group. Exercise performance tests included the 6 min timed walk test (6MTWT), sit to stand transfers in 60 s (STS60), timed up and go 3 m (TUAG) and the Duke's activity status index (DASI), a measure of functional ability.. Friedman's test analyses were performed to assess differences between baseline and 12-month data. Mean body weight reduced by 7.1% from 102.9 kg to 95.7 kg (P<0.001) This equates to a reduction in BMI from 35.7 kg/m(2) at baseline to 33.2 kg/m(2) at 12 months. Waist circumference decreased by 12.9 cm from 112.9 cm to 100.0 cm (P<0.005) at 12 months. The 6MTWT improved by 45% (P<0.001), STS60 by 30% (P<0.001), TUAG by 37% (P<0.001) and DASI by 50% (P<0.001) after 12 months. To date, two of the patients have received live-related renal transplants and an additional seven patients have now been successfully enrolled onto the transplant waiting list.. Preliminary experience from this multidisciplinary programme combining diet, exercise and orlistat suggests that significant weight loss and improved physical functioning can be achieved in obese CKD patients, potentially allowing them the opportunity of kidney transplantation and the associated benefits of this compared with long-term dialysis.

Topics: Adult; Anti-Obesity Agents; Chronic Disease; Combined Modality Therapy; Exercise Therapy; Female; Humans; Kidney Diseases; Lactones; Male; Middle Aged; Obesity; Orlistat; Patient Care Team; Weight Loss

We evaluated the efficiency of a six-month outpatient weight loss treatment program combining healthy diet, fat reduction, psychological counseling, exercise, and orlistat treatment, by measuring body weight and levels of cardiovascular risk factors in 476 subjects with BMI over 30 or 28 with increased blood pressure, cholesterol, and sugar at the baseline and at the end of program. After four weeks of adjustment to a mild low-calorie diet (1600 kcal/day) and counseling, subjects started receiving orlistat (120 mg TID). The mean weight loss after 6 months was 10.9%. Systolic pressure dropped by 6.7%, diastolic by 4.2%, fasting blood glucose by 10.1%, and total cholesterol by 9.8%. Only 9 subjects (7.8%) poorly tolerated the treatment. More men than women were able to maintain the achieved weight loss six months after the program (70.6% vs. 58.3%, respectively). The healthy weight loss program was an efficient approach to obesity treatment.

Topics: Anti-Obesity Agents; Counseling; Exercise Therapy; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; 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

Estimating body composition is important to understand the metabolic and cardiovascular effects of adiposity. Estimating changes in body compartments arising from weight loss strategies is equally important to evaluate their benefits and risks, particularly in frail populations (elderly or diabetic), and following bariatric surgery. Body compartments were evaluated in 50 obese subjects (25 diabetic, 25 non-diabetic) before and after a 7 kg weight loss obtained after 6 months of calorie restriction and orlistat. Fat and fat-free mass (FFM) were estimated by bioelectrical impedance analysis (BIA), dual X-ray absorptiometry (DXA), plethysmography (BodPod) and a combination of these in a 3- or 4-compartment model, the latter being considered the reference method. FFM hydration was the ratio of total body water (BIA) to FFM. FFM hydration was significantly higher than classical values (75.9+/-3.0%, P<0.0001), and decreased with weight loss (74.2+/-3.3%). Compared to the 4-compartment, the 3-compartment model gave the most accurate fat and FFM estimation. A significant bias was observed with DXA, BodPod or BIA. Compartment changes induced by weight loss were accurately evaluated by DXA, being particularly precise in the 3-compartment analysis. No effect of diabetes per se was observed. A 3- or 4-compartmental analysis is necessary to accurately estimate body composition and its changes during weight loss.

Topics: Absorptiometry, Photon; Aged; Body Composition; Body Water; Diabetes Mellitus; Diagnostic Techniques and Procedures; Diet; Electric Impedance; Female; Humans; Lactones; Male; Methods; Middle Aged; Obesity; Orlistat; Plethysmography; Weight Loss

Topics: Animals; Anti-Obesity Agents; Antineoplastic Agents; Drug Approval; Humans; Lactones; Nonprescription Drugs; Orlistat; Weight Loss

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

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

A comparative assessment was made of the short-term effects of orlistat therapy and exercise training on body composition and aerobic fitness in obese females. A total of 24 obese patients were enrolled in to the study; 12 received orlistat therapy (DO) and 12 participated in a regular aerobic exercise-training programme (DE). All patients were on hypocaloric diets. Each patient performed three incremental ramp exercise tests (one at Week 0, one at the end of Week 4 and one at the end of Week 8) to exhaustion using an electromagnetically braked cycle ergometer to determine their anaerobic threshold and maximal exercise (Wmax) capacity. Patients in the DE group performed continuous exercise at a work rate that corresponded to the anaerobic threshold. Weight loss and loss of fat mass after 8 weeks were -6.4% (P=0.002) and -13.4% (DE) vs -5.8% (P=0.002) and -6.4% (P=0.008) (DO), respectively. Wmax capacity was 90.8+/-5 W (basal) vs 92.9+/-5 W (Week 4, P=0.1) and 100.4+/-6 W (Week 8, 10.5%, P=0.04) in the DO group, and 96.2+/-6 W (basal) vs 129.1+/-4 W (Week 4, 34.1%, P=0.002) and 137.5+/-5 W(Week 8, 42.9%, P=0.002) in the DE group. Despite similar decreases in body weight in both groups, patients in the DE group achieved a markedly higher level of Wmax, reflecting a better improvement in cardiopulmonary fitness, compared with patients in the DO group. Considering the improvement of aerobic fitness in the short term, an aerobic exercise-training programme should be considered for sedentary obese patients to improve their aerobic fitness and thereby reduce the negative outcomes of obesity.

Topics: Anaerobic Threshold; Anti-Obesity Agents; Body Composition; Exercise; Female; Humans; Lactones; Obesity; Orlistat; Treatment Outcome; Turkey; Weight Loss

Serum folic acid, but not the vitamin B(12) concentration, was found to be significantly lower in obese subjects than in the control ones.. The aim of this study was to examine the levels of serum vitamin B(12) and folic acid in obese women before and after weight reduction therapy with Orlistat in comparison to healthy controls with normal body weight.. Twenty obese women participated in a 3-month weight reduction therapy. The control group consisted of 20 healthy women.. Body weight and height were measured and BMI was calculated. Body composition was analyzed with the impedance method using a Bodystat analyzer. In all patients before and after 3-month weight reduction therapy, serum concentrations of folic acid and vitamin B(12) were assessed.. In obese women, serum concentrations of folic acid and vitamin B(12) did not change significantly after 3-month weight reduction therapy with Orlistat.

Topics: Adult; Anti-Obesity Agents; Body Height; Body Mass Index; Body Weight; Case-Control Studies; Female; Folic Acid; Humans; Lactones; Middle Aged; Obesity; Orlistat; Vitamin B 12; Weight Loss

Obese patients may have a phase of asymptomatic left ventricular dysfunction. A combined myocardial performance index (MPI) has been demonstrated to be a useful index to estimate left ventricular function and to predict the prognosis of patients with heart failure. The objective of the study was to determine the influence of weight loss on MPI. A total of 18 obese patients (3 men, 15 women, mean age 49.6 +/- 5.5 years, body mass index [BMI] >30 kg/m(2)) were investigated in the study. All patients were treated with a multidisciplinary approach consisting of a hypocaloric diet and orlistat therapy (120 mg three times daily), and all of them underwent two-dimensional and Doppler echocardiographic examination two times before starting the study and after a period of weight loss. Using echo-Doppler methods, ejection fraction, peak velocities of early (E) and late (A) diastolic filling, the E/A ratio, deceleration time (DT), isovolumic contraction time (IVCT), isovolumic relaxation time, ejection time, and MPI were measured. The MPI was obtained by subtraction ejection time from the interval between cessation and onset of the mitral flow. All patients lost at least 10% of their initial body weight, with a mean decrease of 10.8 +/- 3.7 kg. This was associated with significant reductions in BMI with a mean decrease 4.5 +/- 1.4 kg/m(2). Compared with baseline, after weight loss the E/A ratio of 1.01 +/- 0.22 before treatment increased to 1.17 +/- 0.26 (P = 0.012), left ventricular mass index decreased from 88 +/- 23 to 82 +/- 19 g/m(2) (P = 0.028), IVCT from 71 +/- 20 to 53 +/- 30 ms (P = 0.004), DT from 233.65 +/- 38.14 to 196.72 +/- 47.73 s (P = 0.004), and MPI from 0.63 +/- 0.13 to 0.50 +/- 0.13 (P = 0.0001). Weight loss ameliorates MPI and seems to be a clinically relevant measurement of left ventricular global function, and may prove to be a valuable tool in assessing the risk of developing heart failure.

Topics: Anti-Obesity Agents; Body Mass Index; Diet, Reducing; Echocardiography, Doppler; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Prognosis; Prospective Studies; Statistics, Nonparametric; Treatment Outcome; Ventricular Dysfunction, Left; Weight Loss

Orlistat, the first of a new class of drugs for the treatment of obesity, was launched in the UK in December 1998. The prescribing information recommends that treatment with orlistat should be discontinued after 12 weeks if the patient has not achieved a specified loss of weight.. To monitor the safety of orlistat prescribed in the primary care setting in England using prescription-event monitoring (PEM).. A postmarketing surveillance study using the observational cohort technique of PEM. Patients were identified from dispensed prescriptions issued by primary care physicians for orlistat between December 1998 and November 1999. The outcome data were event reports obtained by sending questionnaires (green forms) to the prescribing doctor at least 6 months after the first prescription for an individual patient. Incidence densities, expressed as number of first reports of an event/1000 patient-months of exposure, were calculated. Significant differences between incidence densities (IDs) for events reported in the 1st month (ID(1)) and months 2 and 3 (ID(2-3)) of exposure were regarded as potential signals. Reasons for stopping orlistat were analysed. Follow-up information was requested for selected events and used to assess the causal association with orlistat.. Green forms containing clinically useful information on 16 021 patients (median age 45 years (interquartile range 35-54); 80.1% females) were received. The events reported most frequently during the 1st month of treatment were 'not effective' (639; 4.0% of cohort), diarrhoea (371; 2.3%) and weight loss (230; 1.4%). Twelve clinical adverse events were identified for which ID(1) was significantly greater than ID(2-3). These included non-specific events (e.g. intolerance, malaise/lassitude, unspecified side effects), weight loss and vaginitis/vulvitis. The remaining events were gastrointestinal in nature and included diarrhoea, pain abdomen, flatulence, nausea/vomiting, rectal discharge, faecal incontinence and 'gastrointestinal unspecified' events. A similar pattern of predominately gastrointestinal events was seen for reasons for stopping and suspected adverse drug reactions. Review of selected events for causality revealed 45 events which were assessed as possibly or probably related to orlistat.. This study shows that orlistat is fairly well tolerated. The safety profile of orlistat was similar to the prescribing information and experience reported in the literature.

Topics: Adult; Anti-Obesity Agents; Cardiovascular Diseases; Cohort Studies; Diarrhea; Drug Administration Schedule; England; Female; Gastrointestinal Diseases; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Pregnancy; Pregnancy Outcome; Primary Health Care; Product Surveillance, Postmarketing; Treatment Outcome; Vaginitis; Weight Loss; Withholding Treatment

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Body Mass Index; Caloric Restriction; Diet, Reducing; Exercise Therapy; Gastroplasty; Humans; Lactones; Laparoscopy; Male; Middle Aged; Obesity; Orlistat; Prospective Studies; Quality of Life; Weight Loss

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

Weight loss improves metabolic abnormalities and reduces cardiovascular risk in obese hypertensive patients. To evaluate the impact of a sustained weight loss on coronary risk, 181 hypertensive patients with metabolic syndrome underwent to orlistat therapy, 120 mg, t.i.d., plus diet for 36 weeks. During therapy, Framingham risk scores (FRS) were calculated for determination of coronary heart disease risk in ten years. Body mass index decreased from 35.0 +/- 4.2 to 32.6 +/- 4.5 kg/m(2) (p< 0.0001) and waist circumference from 108.1 +/- 10.1 to 100.5 +/- 11.1 cm (p< 0.0001), at the end of the study period (week 36). Systolic and diastolic blood pressure showed reductions after the two first weeks, which were maintained up to the end of the study. A clear shift to the left in FRS distribution curve occurred at the end of the study, compared to baseline, indicating a reduction in coronary risk. Over all patients at risk, 49.2% moved to a lower risk category. A weight loss > 5% occurred in 64.6% of all patients, associated with improvement in glucose metabolism. Among those with abnormal glucose metabolism, 38 out 53 patients (71.7%) improved their glucose tolerance (p< 0.0005). In conclusion, long-term orlistat therapy helps to reduce and maintain a lower body weight, decreasing risk of coronary disease and improving glucose metabolism, thus protecting against type 2 diabetes.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Female; Follow-Up Studies; Humans; Hypertension; Lactones; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Waist-Hip Ratio; 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

Due to the insurance companies' restrictions, partial reimbursement of orlistat treatment in the Czech Republic is restricted to obese diabetics with BMI >35 who are concurrently treated pharmacologically for dyslipidaemia, hypertension or ischaemic heart disease, with compulsory interruption of minimum 3 months, only after which the treatment can be resumed for another year. We evaluated 32 patients with Type 2 diabetes who underwent such course of treatment, with view of establishing whether the interruption has any detrimental effect on the success of the therapy in terms of weight loss and diabetes compensation. The treatment was well tolerated, producing statistically significant decrease in BMI and triglyceride levels during the first year, which was maintained in the second year. Fasting glucose levels were improved at nearly-significant level. The interruption in treatment between the first and second year had no marked detrimental effect, although the relative failure of the second treatment year to bring further benefits to the patients can certainly be at least partially attributed to this treatment gap.

Topics: Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Lactones; Lipase; Lipids; Middle Aged; Obesity; Orlistat; Weight Loss

Do 'informed' or 'expert' patients challenge dominant traditions in biomedicine or simply adopt these as conventional ways of thinking about body shape and size, illness and health? This paper examines this question in relation to the use of the weight-loss drug Xenical by participants in an Internet forum for obese and overweight people. Ethnographic and interview data from the forum provides evidence that participants share information and support each other as they use Xenical, and in the process emerge as 'expert patients' in relation to their body shape and its treatment. However, it is argued that while an 'expert patient' can be perceived as desirable, enabling the democratisation of healthcare, it can also be constraining. The exchanges between the users in the forum perpetuate a biomedical model of overweight as a condition to be overcome. The discussion critically considers a number of options for the development of the expert patient, including the emergence of an 'informed consumer'.

Topics: Adult; Attitude to Health; Communication; Female; Humans; Internet; Lactones; Lipase; Male; Motivation; Orlistat; Overweight; Patient Education as Topic; Patient Participation; Physician-Patient Relations; Power, Psychological; Self Care; Social Dominance; Social Support; United Kingdom; Weight Loss

A 57-year-old Caucasian woman with Type 2 diabetes treated for seven years with diet and oral combination hypoglycaemic therapy was referred because of the progressive deterioration of glycaemic control. She was obese (77 kg, BMI = 39.9), hypertensive, hypercholesterolaemic with marked osmotic symptoms (HbA(1c) 12.2%), therefore she was started on insulin (Human Mixtard 30 b.d.) with metformin therapy. Dietary counselling, recommendations to increase physical activity, and supervised self-injection technique with titration of her insulin were also provided. She was routinely followed-up to assess her progress. Two years later, her glycaemic control remained suboptimal. Average HbA(1c) was 10.4% despite an increasingly high dose of insulin (94 units/day) although it improved when metformin was increased to 1 g t.d.s. (HbA(1c) = 9.3%). Her BMI progressively rose from 39.9 to 42.1 (77 to 82.5 kg) despite dietary advice. A trial of orlistat (three months) was commenced, after intensive dietary counselling, that reduced her body weight by 1.5 kg (2% reduction, BMI 41.3). However, her HbA(1c) improved by 0.5% (from 9.3 to 8.8%). Six months after orlistat was stopped her HbA(1c) rose to 10.5% and weight increased to 81.8 kg (BMI 41.8). Despite the orlistat treatment broaching NICE guidelines should it have been continued?

Topics: Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Insulin; Lactones; Metformin; Middle Aged; Obesity; Orlistat; Practice Guidelines as Topic; Weight Loss

Inflammation plays a major role in the pathogenesis of atherosclerosis. Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. The aim of this study is to investigate changes in the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) during weight reduction with orlistat treatment in obese patients.. Thirty-six obese (BMI: 36.1 +/- 3.4 kg/m2) and II non-obese (BMI: 22.9 +/- 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05) and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the level of obesity assessed by BMI at baseline. After 6 months of orlistat treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels.. In summary plasma IL-6 and hs-CRP levels were increased in obese patients. Orlistat-induced weight reduction was associated with decreasing levels of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be directly involved in atherogenesis, this would suggest that interventions to reduce IL-6 and CRP levels could be cardioprotective.

Topics: Adult; Anti-Obesity Agents; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation; Interleukin-6; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Topics: Dietary Fats; Enzyme Inhibitors; Female; Humans; Intestinal Absorption; Lactones; Orlistat; Weight Loss

In addition to direct weight reduction, there may be other benefits of obesity treatment including improved insulin sensitivity. The purpose of this study was to characterise concomitant diabetes drug use and the related costs in patients with diabetes treated with orlistat (Xenical) in the first 6 months of treatment.. One hundred overweight patients with diabetes and a body mass index (BMI) > or = 28 kg/m2 were enrolled in a structured UK hospital-based weight management clinic and treated with orlistat plus behavioural interventions. Among other measures, weight, glucose control (HbA1c) and drug treatment were recorded. Subjects were followed-up for a maximum of 24 months at intervals of 1-3 months, with a maximum treatment period of 24 months.. The majority of subjects (91%) had type 2 diabetes. They had a mean age of 55 years and 55% were women. For patients followed up at 6 months, their mean BMI at baseline was 39.5 kg/m2 with a mean HbA1c of 7.6%. The mean weight loss at 6 months was 7.1 kg (p < 0.001). Despite a significant average absolute HbA1c reduction of 0.62% (p < 0.001), the most notable gains were made by those with the highest baseline HbA1c values (a mean relative reduction of 20% for those above the 75th percentile). There were 50 patients treated with insulin at baseline and 47 at 6 months. Of those treated with insulin, the mean dose was 130 units at baseline and 90 units at 6 months (p < 0.001). Twenty patients (44.4%) initially treated with oral hypoglycaemic agents alone reduced their dose after 6 months (not significant). Despite marked improvement in insulin sensitivity (baseline mean, 1.24 units/kg; 6 month mean, 0.90 units/kg [p < 0.001]) there was no correlation with BMI change. The average cost of diabetes treatment at baseline was pound 1.16 per day and pound 0.83 at 6 months (p < 0.001). Age was the only independent predictor for insulin dose reduction.. Orlistat appears to reduce the need for concomitant diabetes medication irrespective of weight loss, a reduction that is likely to represent a large cost offset for orlistat treatment.

Topics: Adult; Aged; Aged, 80 and over; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Lactones; Male; Middle Aged; Obesity; Orlistat; Prospective Studies; Weight Loss

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

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

Topics: Adolescent; Adult; Anti-Obesity Agents; C-Reactive Protein; Cholesterol, LDL; Diet, Reducing; Endothelium, Vascular; Female; Humans; Insulin; Lactones; Leptin; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Weight Loss

Topics: Anti-Obesity Agents; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Lactones; Obesity; Orlistat; 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

Orlistat is an inhibitor of lipase which splits triglycerides into free fatty acides and glycerol. This drug, by inhibiting hydrolysis of triglycerides, is the cause of significant loss of fat in the faeces. 13 obese and 15 nonobese subjects were examined. Obese subjects received orlistat (Xenical, F. Hoffmann La Roche Ltd, Switzerland) 3 x 120 mg/d. Treatment with orlistat for 16 weeks was followed by a significant fall of BMI and MAP, insulinemia, insulin/glucose ratio, leptinemia, serum total cholesterol, triglycerides, HDL-cholesterol and 25-OH-D concentration respectively. Orlistat did not influence significantly serum LDL-cholesterol concentration but unexpectedly increased plasma levels of folic acid, vitamin B12 and NPY.. (1) Monitoring of plasma 25-OH-D levels in obese patients on orlistat therapy seems to be mandatory. (2) In spite of significant changes (in opposite direction) in leptinemia and serum NPY level observed in obese subjects treated with orlistat, presence of a functional relationship between these hormones could not be confirmed.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Carbohydrates; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Enzyme Inhibitors; Female; Hormones; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Lactones; Leptin; Lipase; Lipids; Male; Neuropeptide Y; Obesity; Orlistat; Poland; Time Factors; Treatment Outcome; Triglycerides; Vitamins; 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

Orlistat treatment of obesity results in a poor long-term weight loss (< 5%) in about 30% of patients.. Total energy and macronutrient intake were examined to assess the effect of a change in eating habits on weight loss.. Sixty-two patients consumed a hypocaloric diet, together with orlistat (3 x 120 mg/day), for 72 weeks, with a maximal fat allowance of 30% of the energy intake. At regular intervals, food diaries were recorded.. Fifty-six patients completed the study and lost 8.5 +/- 0.88 kg (P < 0.001). Energy intake was approximately 1500 kcal/day during the entire study period. In three sub-groups established according to weight loss (1, < 5%; 2, > 5% and < 10%; 3, > 10%), fat intake was within the recommended range in all groups during the first 6 months, but thereafter only in group 3. All groups increased their carbohydrate consumption, with the greatest increase in group 1, which could account for the rapid regain of initially lost body weight in this group.. At the beginning of a weight management programme in conjunction with orlistat, a low fat intake is advised for an efficient reduction in body weight. Subsequently, in patients with poor long-term weight loss, dietary recommendations must also consider carbohydrate restriction to ensure an adequate hypocaloric diet.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Body Mass Index; Diet, Fat-Restricted; Dietary Carbohydrates; Energy Intake; Feeding Behavior; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

A 17-year-old obese boy found to have familial apical hypertrophic cardiomyopathy on routine screening was enrolled in a weight loss program on the basis of the hypothesis that significant weight loss would improve his cardiac status. He was followed with serial dual-energy x-ray absorptiometry, electrocardiography, echocardiography, and blood pressure and pulse rate measurements. Within 1 year, he lost 49 kg, with a body mass index reduction from 43.6 to 28.1 kg/m2 and associated reductions in systolic blood pressure, diastolic blood pressure, pulse pressure, mean heart rate, rate pressure product, and echocardiographic indices of left ventricular mass that resulted in a change from the initial geometric finding of eccentric left ventricular hypertrophy to a "normal" left ventricular mass with minimal asymmetric apical left ventricular thickening. Significant weight loss in an obese adolescent with presumed familial apical hypertrophic cardiomyopathy was associated with striking improvement in cardiac functional indices, which could have profound implications for long-term cardiovascular risk.

Topics: Adolescent; Anti-Obesity Agents; Cardiomyopathy, Hypertrophic, Familial; Humans; Lactones; Male; Obesity; Orlistat; Weight Loss

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

Obesity is on the increase yet within the National Health Service (NHS) treatment approaches differ greatly and service is patchy. Our aim was to compare current practice within a general dietetic clinic with a new clinic developed specifically for patients of higher morbidity risk.. Locally referred patients to the dietitians from within or without Hammersmith Hospitals NHS Trust of higher morbidity risk were invited to attend a new Lifestyle Clinic. Treatment was of a contractual nature and included more time with the dietitian, the offer of pharmacotherapy if appropriate and an emphasis on achieving a realistic weight loss of 10% within a 6-month period. Cognitive behavioural strategies were utilized focusing on achieving changes in dietary intake and physical activity levels.. A total of 103 patients have been enrolled of whom 34 have been discharged before completion of the clinic programme. Twenty-six patients have completed (18 started pharmocotherapy with Orlistat and eight remained on lifestyle advice only), with the remainder still attending the Lifestyle Clinic. The results for these 26 patients demonstrate clinically significant benefits with regard to exercise tolerance 390.8 +/- 37.5 m vs. 473 +/- 46.6 m (P < 0.001), waist measurement 121.5 +/- 4.4 cm vs. 110.9 +/- 3.6 cm (P < 0.001), and total cholesterol : HDL ratio 1.17 +/- 0.05 mmol L-1 vs. 1.27 +/- 0.07 mmol L-1 (P < 0.05). A weight loss comparison with historical data collected in the general dietetic clinic achieves a 7.8 +/- 0.7 kg reduction in weight (with pharmocotherapy 8.96 +/- 0.98 kg, with lifestyle only 5.23 +/- 0.657) vs. 1.7 +/- 0.4 kg (P < 0.05).. Lifestyle clinics facilitate beneficial lifestyle changes which impact positively on morbidity risk factors demonstrating an improvement on current service offered within the NHS. There is an obvious resource implication of offering an intensive management package. There is need for a randomized control trial with analysis to evaluate whether there is cost benefit from this type of intervention.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Behavior Therapy; Body Constitution; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise; Female; Health Behavior; Humans; Lactones; Life Style; Male; Middle Aged; Obesity; Orlistat; Patient Education as Topic; Risk Factors; Treatment Outcome; Weight Loss

Adjustable gastric banding (AGB) is frequently performed to treat morbid obesity. One problem which can occasionally develop after a restrictive procedure is consumption of a high calorie liquid diet, which may prohibit further weight loss. Orlistat, a newly developed intestinal lipase inhibitor, prevents absorption of about one-third of ingested fat. It is unknown whether patients no longer losing weight after AGB, despite further band restriction, may lose weight with addition of orlistat.. 38 patients were selected who had stopped losing weight 3 months before the initiation of the study, 18 +/- 6 months (mean +/- SEM) after laparoscopic AGB. Subjects were divided into 2 groups, matched for age, sex, filling volume of the band and body mass index (BMI) both at the time of surgery and start of the study (18 +/- 6 months after AGB).. Patients in group A received dietary counseling and orlistat 120 mg TID for 8 months, while patients in group B received only dietary counseling. During the following 8 months of study, subjects in group A lost 8 +/- 3 kg in weight, whereas subjects in group B lost 3 +/- 2 kg (p < 0.01, months 18 vs 26 of study; p < 0.03, group A vs B). In 15 patients from group A the study was further extended 9 months, but interestingly, weight remained stable independent of whether orlistat was continued (n = 8) or stopped (n = 7). 4 subjects were excluded from the extension study because of additional malabsorptive bypass surgery. Subjects taking orlistat encountered only minor GI side-effects.. Orlistat appears to be useful when added in patients after AGB who are no longer losing weight, perhaps due to a high-calorie liquid diet rich in fat.

Topics: Anti-Obesity Agents; Female; Gastroplasty; Humans; Lactones; Male; Middle Aged; Obesity, Morbid; Orlistat; Postoperative Period; Weight Loss

We treated 44 individuals, 31 women and 13 men, for 12 months; each one had a body mass index > or = 28 kg/m2. Mean age was 53 years (range 20-75 years). Each individual visited a nurse regularly for diet recommendations, and each was provided a prescription for orlistat from his or her own doctor. The target weight loss of 2.5 kg prior to treatment with orlistat was obtained by 28 patients. After 3 months the average weight loss was 3.3 kg, and after 6 months, when 10 women and 6 men remained, the average weight loss was 6.1 kg and 6.5 kg respectively. The average weight decrease between 6 and 12 months was 0.3 kg and 2.7 kg for 7 women and 4 men respectively. Total cost for medical staff's working hours was approximately 700 Swedish crowns per kg weight loss. This cost seems rather high in comparison with the unsatisfactory results obtained for the group as a whole.

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Community Health Centers; Cost-Benefit Analysis; Female; Health Care Costs; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Practice Guidelines as Topic; Sweden; Treatment Outcome; Weight Loss

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

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; Humans; Hypertension; Lactones; 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

To study the prescribing of the antiobesity drug orlistat in relation to the approved indication and its weight-reducing effect in clinical practice during the first 3 months of treatment.. Anonymous postal questionnaire survey to prescribers of orlistat concerning a random sample of 1000 of 20,000 prescriptions.. Useful information was obtained for 789 patients.. Primary and secondary care in Sweden.. Beginning and continued treatment according to the approved indication. Dropout from treatment. Weight loss during treatment.. Four percent of the patients were prescribed orlistat despite having a body mass index (BMI) less than 28 kg/m2. Only 24% of the patients had a diet period with a weight loss of 2.5 kg or greater before the start of therapy. Half of the patients with a weight loss of less than 5% after 3 months continued the treatment. Ten percent gained weight or had no weight loss at all while 43% lost less than 5% in weight. At least one-quarter of the patients stopped the treatment within the observation period.. Orlistat was not prescribed according to the approved indication in the majority of cases. The dropout rate was high and most patients had minor gain from the treatment.

Topics: Adult; Anti-Obesity Agents; Cohort Studies; Drug Prescriptions; Female; Humans; Lactones; Male; Middle Aged; Orlistat; Sweden; Treatment Refusal; Weight Loss

Topics: Anti-Obesity Agents; Diet, Reducing; Digestive System; Double-Blind Method; Humans; Lactones; Orlistat; Treatment Outcome; Weight Loss

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

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

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

Topics: Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lactones; Male; Metformin; Middle Aged; Obesity; Orlistat; Weight Loss

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

Orlistat (tetrahydrolipstatin), launched by Roche under the trade name Xenical, is a selective inhibitor of pancreatic and gastro-intestinal lipases. It reduces the digestion of dietary fat and its resorption through digestive mucosa by around 30%. It is indicated, at a dose of 3 x 120 mg/day (one dose with each meal) and together with a moderately low-calorie and low-fat diet, for the treatment of obesity. It has been shown, in placebo-controlled two-year trials, to almost double the number of obese subjects who succeed in loosing at least 10% of initial body weight. Independently, it contributes to decrease serum cholesterol levels by 6-10%. Because of its mechanism of action, this drug can induce intestinal side-effects which tend to decrease with time and with the reduction of fat intake, thus improving diet compliance.

Topics: Dietary Fats; Enzyme Inhibitors; Humans; Hypercholesterolemia; Lactones; Obesity; Orlistat; Weight Loss

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

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

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Diabetes Mellitus; Enzyme Inhibitors; Female; Health Care Costs; Humans; Hypertension; Lactones; Lipase; Male; Middle Aged; Morbidity; Obesity; Orlistat; Risk Factors; United States; Weight Loss

Topics: Clinical Trials as Topic; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Male; Multicenter Studies as Topic; Obesity; Orlistat; Weight Loss

Topics: Diet, Fat-Restricted; Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Weight Loss

Topics: Body Mass Index; Enzyme Inhibitors; Humans; Lactones; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

Ninety-two patients in long-term treatment for obesity completed a questionnaire on the weight development of their close family members. Of 47 such relatives, 37 had lost a mean of 6.1 kg and 10 increased a mean of 5.1 kg. Treatment of obesity will affect many more than those taking part in the actual program and generally result in weight loss. This effect on family members was mostly considered beneficial.

Topics: Adult; Aged; Behavior Therapy; Combined Modality Therapy; Exercise; Family; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Retrospective Studies; Weight Loss