orlistat and Obesity

Obesity is recognized as a true chronic disease and an independent risk factor for kidney disease. In particular, a correlation was observed between obesity and the development of focal segmental glomerulosclerosis. The clinical consequences of obesity on the kidney can include albuminuria, nephrotic syndrome, nephrolithiasis, and increased risk of development and progression of renal failure. Conventional therapy, which includes low-calorie diet, exercise, lifestyle changes, and drug therapy, including GLP1-RA, phentermine, phentermine/topiramate, bupropion/naltrexone, orlistat, is not always able to achieve the desired results and above all does not guarantee stabilization of body weight over time. On the other hand, bariatric surgery is giving excellent results in terms of efficacy and duration. Bariatric surgery techniques that are generally divided into restrictive, malabsorptive, and mixed are not free from possible metabolic complications such as anemia, vitamin deficiency, and stones. However, they are able to ensure a good maintenance of weight loss obtained with disappearance or reduction of the incidence and severity of comorbidities related to obesity.

Topics: Anti-Obesity Agents; Humans; Kidney; Obesity; Orlistat; Phentermine

Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity. In addition to being regarded as a slimming drug, a growing number of studies in recent years have suggested that orlistat has anti-tumor activities, while the underlying mechanism is still not well elucidated. This paper reviewed recent pharmacological effects and mechanisms of orlistat against tumors and found that orlistat can target cancer cells through activation or suppression of multiple signaling pathways. It can induce tumor cells apoptosis or death, interfere with tumor cells' cycles controlling, suppress fatty acid synthase activity, increase ferroptosis, inhibit tumor angiogenesis, and improve tumor cells glycolytic. Thus, this review may shed new light on anti-tumor mechanism and drug repurposing of orlistat, and anti-tumor drug development.

Topics: Apoptosis; Drug Repositioning; Glycolysis; Humans; Obesity; Orlistat

Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and Drug Administration (FDA) for chronic weight management. The aim of this paper is to investigate the pharmacoeconomic evaluation of AODs through a systematic review with a special focus on methodological considerations.. We searched the general and specific databases to identify the primary pharmacoeconomic evaluation of AODs.. A total of 18 full-text articles and three conference abstracts were included in this review. Most of the economic assessments were still about Orlistat. And the observations we could make were consistent with the previous systematic review. A few studies were on the combined therapies (i.e. PHEN/TPM ER and NB ER) compared to different comparators, which could hardly lead to a generalized summary of the cost-effectiveness. Most recently, pharmacoeconomic evidence on the newest GLP 1 RA approved for the indication of obesity or obesity with at least one comorbidity emerged gradually. Modelling-based cost-utility analysis is the major type of assessment method. In the modelling studies, a manageable number of the key health states and the state transitions were structured to capture the disease progression. In particular, the principal structure of the decision model adopted in the three studies on the newly approved drug was nearly the same, which enables more in-depth comparisons and generalizations of the findings.. This study provided an up-to-date overview of the strengths and areas for improvement in the methodological design of the pharmacoeconomic evaluation of the licensed drugs for chronic weight management. Future modelling evaluations would benefit from a better understanding of the long-term weight loss effects of the current therapeutic options and the weight rebound process after the discontinuation of treatment.. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302648, identifier CRD42022302648.

Topics: Anti-Obesity Agents; Comorbidity; Economics, Pharmaceutical; Humans; Obesity; Orlistat; United States

This meta-analysis was conducted to compare the effect and safety of oral contraceptive pills (OCP) plus orlistat with OCP alone in clinical, hormonal, and lipid metabolism outcomes in patients with polycystic ovary syndrome (PCOS) and overweight/obesity.. Pubmed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and SinoMed were systematically reviewed. A random-effects or fixed-effects model was used to pool the estimate.. Eight studies were included in this meta-analysis. Significant reductions in BMI, WHR, and waist circumference were observed in combination group as compared with OCP alone group. Regarding the hormonal outcome, T, SHBG, FAI, LH, DHEAS, FSH, and E2 levels were significantly improved in combination group compared with OCP alone group. However, the TT and FT did not change significantly between the two groups. Regarding the lipid metabolism outcomes, TC, LDL-C, and TG levels were reduced and HDL-C level was increased in the combination group. Regarding the insulin metabolism outcomes, FINS and HOMA-IR levels were reduced in combination group than in OCP group. The ovulation rate, pregnancy rate, and overall effective rate were significantly higher in combination group than in OCP alone group. Fewer complications were observed in the combination group than in OCP group, and the difference between them was significant.. This combination treatment of OCP and orlistat was more effective than OCP alone in reducing the weight, hormonal, lipid, and insulin metabolism profiles, as well as improving the ovulation rate, pregnancy rate, and overall effective rate, as compared with OCP alone.

Topics: Contraceptives, Oral, Combined; Female; Humans; Insulins; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Pregnancy

Obesity is closely associated with nonalcoholic fatty liver disease (NAFLD), a highly prevalent disease without any approved medication. The aim of this review was to summarize the evidence on the effect of anti-obesity medications on NAFLD, especially focusing on hepatic histology.. Orlistat and some glucagon-like peptide-1 receptor analogs, including liraglutide and semaglutide, have beneficial effects on hepatic steatosis and inflammation, but not fibrosis. Other anti-obesity medications, including lorcaserin, setmelanotide, phentermine hydrochloric, phentermine/topiramate, and naltrexone/bupropion, have been minimally investigated in NAFLD. Furthermore, medications like sodium-glucose cotransporter-2 inhibitors and farnesoid X receptor have shown beneficial effects in both NAFLD and obesity, but they have not been licensed for either disease. Liraglutide, semaglutide, and orlistat may be currently used in selected patients with obesity and NAFLD. Further research is warranted, since targeting obesity may provide additional benefits on its comorbidities, including NAFLD.

Topics: Anti-Obesity Agents; Humans; Liraglutide; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phentermine; Sodium-Glucose Transporter 2 Inhibitors

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

Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs).. While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed.. The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.

Topics: Anti-Obesity Agents; Bupropion; Drug Therapy, Combination; Humans; Liraglutide; Liver Cirrhosis; Liver Transplantation; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; Translational Science, Biomedical

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

Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease. Formation of complex lipid membranes and palmitoylation of coronavirus proteins are essential during viral replication and assembly. Inhibition of fatty acid synthase (FASN) and restoration of lipid catabolism by activation of AMP-activated protein kinase (AMPK) impede replication of coronaviruses closely related to SARS-coronavirus-2 (CoV-2). In vitro findings and clinical data reveal that the FASN inhibitor, orlistat, and the AMPK activator, metformin, may inhibit coronavirus replication and reduce systemic inflammation to restore immune homeostasis. Such observations, along with the known mechanisms of action for these types of drugs, suggest that targeting fatty acid lipid metabolism could directly inhibit virus replication while positively impacting the patient's response to COVID-19.

Topics: AMP-Activated Protein Kinases; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Digestive System; Fatty Acid Synthases; Fatty Acids; Humans; Lipid Metabolism; Metformin; Obesity; Orlistat; SARS-CoV-2; Viral Proteins; Virus Assembly; Virus Replication

Topics: Anti-Obesity Agents; COVID-19; Diabetes Mellitus; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Metformin; Obesity; Orlistat

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 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 is a major cause of type 2 diabetes and may complicate type 1 diabetes. Weight loss for obese individuals with diabetes has many health benefits, often leads to improvement in glucose control and sometimes, in type 2 diabetes, near normalisation of abnormal glucose metabolism. Weight loss is difficult to maintain and attempts to lose weight may be undermined by some diabetes treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst lifestyle support should be the primary approach to aid individuals who wish to lose weight, pharmacological approaches can also be considered. These include choosing glucose-lowering drugs or drug combinations that are weight neutral or result in weight loss or prescribing drugs that are specifically approved as anti-obesity medication. Given that some of the newer glucose-lowering medications that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are also being used or considered for use as anti-obesity drugs, it seems that the distinction between glucose-lowering medication and weight loss medication is becoming blurred. This review discusses the main pharmacological approaches that can be used to support weight loss in individuals with diabetes.

Topics: Animals; Benzazepines; Bupropion; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Lactones; Naltrexone; Obesity; Orlistat

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

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

Lipases are enzymes that catalyse the hydrolysis of ester bonds of triglycerides ranging among biocatalysts of considerable physiological significance and industrial potential. Better understanding of the catalytic functions and achieving the possibility to control the biocatalysis process, in particular exploring some activators and inhibitors of lipases, seems to be crucial in the context of novel applications. The lipase activity is a function of interfacial composition: the enzyme can be there activated as well as denaturated or deactivated and the interface is an appropriate site for modulating lipolysis. Lipase inhibitor, interacts directly with the enzyme and inhibits lipase action. Alternatively, some compounds can postpone the lipolytic reaction via adsorption to the interphase or to the substrate molecules. The aim of this review is to summarise the current knowledge concerning human, animal and microbial lipase inhibitors, which were grouped into two categories: synthetic lipase inhibitors (including phosphonates, boronic acids and fats analogues) and natural compounds (including β-lactones and some botanical foodstuffs - plant extracts and plant metabolites, mainly polyphenols and saponins as well as peptides and some dietary fibers). The topics discussed include also inhibition issues from the viewpoint of obesity treatment. Among natural compounds able to inhibit lipase activity are β- lactones including orlistat. Orlistat is the only registered drug for obesity treatment in many countries and lipases are essential enzymes for lipid absorption - thus fat absorption or obesity can be controlled by lipase inhibition, especially pancreatic lipase which is responsible for the hydrolysis of over 80% of total dietary fats. Its effectiveness in obesity treatment was also described.

Topics: Animals; Boronic Acids; Enzyme Inhibitors; Fatty Acids; Humans; Lactones; Lipase; Obesity; Organophosphonates; Orlistat; Plant Extracts; Surface-Active Agents

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

To review the currently available pharmacotherapies for obesity management with a particular focus on the United States.. Narrative review based on literature searches and the latest prescribing information (up to July 2017).. Obesity pharmacotherapies may assist those individuals who have obesity, or overweight with comorbidities, who have failed to maintain weight loss with lifestyle modifications alone (caloric restriction and increased physical activity). Currently approved options in the United States include phentermine for short-term use and five obesity pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an obesity pharmacotherapy is indicated, treatment should be selected to provide the most appropriate option for each individual and their circumstances. Variables such as contraindications, individual comorbidities, patient choice, patient readiness to incorporate additional behavioral changes (e.g., alcohol prohibition), and cost should guide choices.. Each of the obesity pharmacotherapies has advantages and disadvantages that can help guide treatment choice. Those receiving treatment may also have individual preferences based on factors such as administration route, frequency of dosing, and/or safety profile. In addition, some options may be particularly appropriate for patients with common obesity-related complications such as depression or diabetes.

Topics: Adult; Anti-Obesity Agents; Benzazepines; Female; Humans; Lactones; Liraglutide; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Risk Reduction Behavior; United States

Weight-loss drugs are being evaluated for their role in obesity management. This article reviews the available weight-loss drugs, their efficacy and side effects, and their best clinical use.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Bupropion; Drug Combinations; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

Topics: Androgens; Anti-Obesity Agents; Antidepressive Agents; Antihypertensive Agents; Antipsychotic Agents; Appetite Depressants; Benzazepines; Bupropion; Drug Combinations; Fructose; Humans; Hypoglycemic Agents; Hypogonadism; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Testosterone; Topiramate; Weight Gain

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

Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities.

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

To review the efficacy and safety of liraglutide, marketed as Saxenda, a glucagon-like peptide-1 analog for obesity management.. A MEDLINE search (1970 to March 2015) was conducted for English-language articles using the terms glucagon-like peptide 1, liraglutide, and obesity.. Published articles pertinent to the efficacy and safety of liraglutide for short- and long-term obesity management among overweight or obese patients and special populations were reviewed and summarized.. Based on randomized placebo-controlled and active-comparator studies, liraglutide can increase weight loss among overweight and obese patients in a dose-dependent manner with once-daily doses of 1.2 to 3.0 mg. It has been shown that a higher proportion of patients experienced 5% and 10% weight loss from baseline compared with placebo and orlistat. Data support the potential benefit of liraglutide among overweight and obese patients with prediabetes, as well as women with polycystic ovary syndrome (PCOS) with an inadequate response to metformin. Larger and more robust studies are needed to determine the clinical significance of liraglutide among other agents for obesity in diverse populations.. Liraglutide is an adjunct to lifestyle modifications to improve success rates among overweight or obese individuals without diabetes. It may have a potential role in special populations, such as in those with prediabetes and women with PCOS. Based on its clinical evidence, liraglutide can result in more weight loss from baseline compared with orlistat and placebo. Adverse events associated with liraglutide are primarily gastrointestinal and usually dose dependent.

Topics: Anti-Obesity Agents; Female; Humans; Injections, Subcutaneous; Lactones; Life Style; Liraglutide; Obesity; Orlistat; Polycystic Ovary Syndrome; Prediabetic State; Randomized Controlled Trials as Topic

Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion.

Topics: Animals; Anti-Obesity Agents; Enzyme Inhibitors; Flavonoids; Humans; Lactones; Lignans; Lipase; Lipid Metabolism; Obesity; Orlistat; Pancreas; Polyphenols

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

Topics: Anti-Obesity Agents; Appetite; Appetite Depressants; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Approval; Drug Combinations; Drug Discovery; Energy Metabolism; Enzyme Inhibitors; Fructose; Glucagon-Like Peptide 1; Humans; Hypothalamus; Lactones; Lipase; Liraglutide; Metabolic Syndrome; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate

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

Obesity is a very common disease with very difficult treatment. Most patients are not able to change their behaviour. Most hopeful for the future is a safe pharmacotherapy which could be widely used. In this review, old and potentially new drugs decreasing weight are mentioned (centrally acting anorectics, orlistat, incretine analogues and gliphlozines). Review of newly in U.S.A used antiobesitics is also mentioned. Finally potentially new principles of obesity pharmacotherapy are enumerated.

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

Orlistat, an inhibitor of intestinal lipase, has been available for the treatment of obesity for nearly two decades. In conjunction with a hypocaloric diet, orlistat treatment results in a placebo-subtracted reduction in body weight of around 3 kg at 1 year, and increases the likelihood of achieving clinically significant (≥5%) weight loss by around 20%. Orlistat-induced weight loss also confers modest improvements in systolic and diastolic blood pressure, low-density lipoprotein (LDL) cholesterol, glycemic parameters, and progression to diabetes in people with impaired glucose tolerance. Overall, it has a good safety profile, and serious adverse events (including reports of severe kidney and liver injury) are rare. However, a high rate of gastrointestinal side effects limits adherence to treatment.

Topics: Anti-Obesity Agents; Body Weight; Gastrointestinal Diseases; Humans; Lactones; Medication Adherence; Obesity; Orlistat; Risk Assessment

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

Topics: Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Benzazepines; Fructose; Humans; Lactones; Middle Aged; Obesity; Orlistat; Phentermine; Topiramate

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 incidence of obesity and its associated comorbidities have significantly increased over the years with adverse health and financial consequences for society. Lifestyle changes are essential for the prevention and treatment of obesity but their benefit appears limited as inadequate and nonsustained weight loss results have been reported. Pharmacotherapy is frequently advocated as part of a weight loss strategy. In this review, we will discuss the antiobesity drugs with Food and Drug Administration approval and their cardiovascular implications.. Orlistat (Xenical) remains the single monotherapy that has approval in Europe. Topiramate (Topamax) and phentermine have long been approved in the United States, whereas lorcaserin and the extended release combination of phentermine with topiramate have recently gained approval. The development of single peptides targeting gut hormones or other host signals related to obesity may represent promising therapeutic options.. Despite the recent failures of a number of antiobesity drugs, the pharmacotherapy of obesity is progressing rapidly. Treating the obese cardiovascular patient has proven challenging. Efficacy, safety and the sustainability of weight loss are key areas of focus in drug development strategies.

Topics: Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate

Despite being one of the most prevalent chronic diseases, obesity was not recognized as such until very recently. Although linked to ubiquitous diseases like diabetes, hypertension, coronary artery disease, obstructive sleep apnea, and many others, targeted treatments are few. Diet, exercise, and behavior modification are the pillars of weight loss. When they alone do not achieve the required weight reduction, medications may be used for patients with a BMI above 30 or above 27 if obesity-related comorbidities are present. The spectrum of pharmacologic agents aimed at obesity treatment will be reviewed.. Two medications, phentermine and orlistat, have been the only agents approved many years ago and now still standing. Others have come and gone, removed from the market by the Food and Drug Administration (FDA) because of harmful side-effects. However, in the last few years, new drugs have started to emerge. Since 2012, two new medications phentermine-topiramate extended-release combination and lorcaserin have been FDA approved, while at least one more, naltrexone SR/bupropion SR combination is expected to be re-evaluated by the FDA in 2014.. Treating obesity is crucial as it will ultimately result in the prevention of many related chronic diseases and will decrease morbidity and mortality. Weight loss medications are a valuable part of the clinician's toolbox in the treatment of obesity and should be used when appropriate. Having a variety of medications would be a great asset to accommodate various patients' needs and pre-existing medical conditions.

Topics: Anti-Obesity Agents; Delayed-Action Preparations; Drugs, Investigational; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate; Weight Reduction Programs

Topics: Anti-Obesity Agents; Humans; Lactones; Nephrology; Obesity; Orlistat; Renal Insufficiency, Chronic; Uremia

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

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

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

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

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

Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one.

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

Orlistat is an oral gastrointestinal lipase inhibitor and is indicated for treatment of obesity in combination with a hypocaloric diet. Post-marketing reports of adverse reactions revealed hints for possible drug-induced liver injury which has prompted changes to the product information. Orlistat's development program, involving over 30,000 patients, did not indicate a hepatic safety issue.. We analyzed liver function test data from randomized clinical trials of orlistat, using i) meta-analysis of published study safety data, ii) time-to-event analysis for individual patients, and iii) a novel and more sensitive method derived from the U.S. Food and Drug Administration's (FDA) evaluation of drug-induced serious hepatotoxicity (eDISH) technique. Over 10,000 subjects were included.. The combined odds ratio from a simple summary-level fixed-effects meta-analysis of treatment-emergent abnormalities in serum alanine aminotransferase (ALT) (defined as greater than the upper level of normal for 2 successive measurements) was 1.09 (95% CI 0.93-1.28), and in total bilirubin 1.24 (95% CI 1.03-1.49). Part of the small apparent effect was due to longer exposure to orlistat than to placebo, on average. A patient-level display, adjusting for regression towards the mean, and Kaplan-Meier analysis of changes in ALT and bilirubin, taking account of different exposure, showed no significant difference between orlistat and placebo. This shows that there is no signal for hepatic damage in clinical studies of orlistat.. While idiosyncratic liver injury following exposure to orlistat cannot be excluded, it is likely to be extremely rare.

Topics: Alanine Transaminase; Anti-Obesity Agents; Bilirubin; Humans; Kaplan-Meier Estimate; Lactones; Liver; Obesity; Odds Ratio; Orlistat

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

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

Obesity in rapidly developing countries has recently become an epidemic. That is why the need to fight against this chronic disease is becoming more and more apparent. In order to lose weight it is necessary to achieve negative energy balance either by increasing physical activity or using a low calorie diet. When these methods are ineffective, pharmacotherapy is used. The criterion for the application of medical treatment is a BMI above 30 kg/m2 or above 27 along with the presence of other risk factors. Drugs for weight loss fall into three groups: appetite inhibitors, those increasing energy expenditure by enhancing thermogenesis and those inhibiting the absorption of food in the intestines. This paper presents an overview of these classes of drugs and dietary supplements with an emphasis on their adverse effects and the possibility of poisoning. Despite the fact that in Poland only one drug - orlistat has been registered for the treatment of obesity, the availability of other products is unlimited due to the Internet. This fact, and the tendency of patients to treat obesity by themselves using pharmacological substances, poses a major threat and a challenge to the toxicologist.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Weight; Energy Metabolism; Humans; Lactones; Obesity; Orlistat

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

To provide information regarding evidence-based interventions and clinical practice guidelines as a basis for a clinical toolkit utilizing a step management approach for the primary care provider in managing childhood obesity.. Evidence-based literature including original clinical trials, literature reviews, and clinical practice guidelines.. Interventions can be stratified based on initial screening of children and adolescents so that selection of treatment options is optimized. For all treatments, lifestyle modifications include attention to diet and activity level. Levels of initial success, as well as maintenance of target body mass index, may be related to the intensity and duration of interventions; involvement of family may increase success rates. For failed lifestyle interventions, or for patients with extreme obesity and/or certain comorbidities, pharmacologic or surgical options should be considered.. Many intensive programs have shown success, but the resources required for these approaches may be unavailable to the typical community provider and family. However, using current guidelines, the primary care provider can initiate and manage ongoing interventions in pediatric obesity. A toolkit for primary care implementation and maintenance interventions is provided.

Topics: Adolescent; Anti-Obesity Agents; Bariatric Surgery; Body Mass Index; Child; Humans; Hypoglycemic Agents; Lactones; Life Style; Metformin; Obesity; Orlistat; Pediatrics; Physicians, Primary Care; Primary Health Care; Risk Factors

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

Overweight and obesity in adults are common and adversely affect health.. To summarize effectiveness and harms of primary care-relevant weight-loss interventions for overweight and obese adults.. MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to September 2010; systematic reviews for identifying trials before 2005.. Two investigators appraised 6498 abstracts and 648 articles. Clinical trials were included if control groups received minimal interventions. Articles were rated as good, fair, or poor by using design-specific criteria.. One investigator abstracted study characteristics and findings for good- and fair-quality studies; a second checked them.. Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants after 12 to 18 months, with more treatment sessions associated with greater loss. Limited data suggest weight-loss maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in 3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin resulted in less weight loss. Data on effects of weight-loss treatment on long-term health outcomes (for example, death and cardiovascular disease) were insufficient. Weight-loss treatment reduced diabetes incidence in participants with prediabetes. Effects on intermediate outcomes (for example, lipids and blood pressure) were mixed and small. Data on serious medication harms were insufficient. Medications commonly caused withdrawals due to gastrointestinal symptoms.. Few studies reported health outcomes. Behaviorally based treatments were heterogeneous and specific elements were not well-described. Many studies could not be pooled because of insufficient reporting of variance data. Medication trials had high attrition, lacked postdiscontinuation data, and were inadequately powered for rare adverse effects.. Behaviorally based treatments are safe and effective for weight loss and maintenance.. Agency for Healthcare Research and Quality.

Topics: Anti-Obesity Agents; Behavior Therapy; Combined Modality Therapy; Diet, Reducing; Evidence-Based Medicine; Humans; Lactones; Obesity; Orlistat; Overweight; Patient Dropouts; Primary Health Care; Treatment Outcome

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

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

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

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

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

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

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

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

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

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

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

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

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 currently an epidemic across the globe. Obese patients unable to achieve significant weight loss with lifestyle changes alone may require drug therapy. Clinical trials have shown that orlistat administration may not only lead to weight loss but also protect against type 2 diabetes in around 37% of cases. Orlistat can induce and maintain weight loss, even in patients with comorbid conditions such as hypertension or type 2 diabetes. Recently, orlistat can induce marked weight loss in individuals with chronic kidney disease (CKD). In small numbers of individuals especially those with CKD, orlistat administration may precipitate oxalate nephropathy and renal stone disease. The focus of this article is to review current studies showing impact of orlistat on renal function and outcomes.

Topics: Anti-Obesity Agents; Calcium Oxalate; Humans; Kidney Diseases; Lactones; Obesity; Orlistat

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

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

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

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

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

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

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

Topics: Anti-Obesity Agents; Contraindications; Drug Interactions; Humans; Lactones; Obesity; Orlistat

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

Obesity has rapidly become a life-threatening epidemic worldwide. There are a plethora of obesity-related co-morbidities and complications that increase morbidity, mortality and cost of care associated with obesity. Orlistat is approved for the treatment of obesity and has been evaluated both in obesity and in the several obesity-related co-morbidities.. The purpose of this article is to provide detail of the pharmacotherapeutic role of orlistat in obesity, describe orlistat and its pharmacological properties, critique the evidence for orlistat's use in obesity and obesity related co-morbidities, and define the role of orlistat in clinical practice.. A thorough, all-inclusive literature search was conducted to isolate clinical trials, case reports and meta-analyses evaluating the safety and efficacy of orlistat in various patient populations.. Orlistat's unique mechanism of action, beneficial effects on multiple co-morbidity surrogates and relatively mild adverse effect and drug interaction profile position it favorably as the first option for pharmacotherapy in comprehensive obesity management of adults and children.

Topics: Animals; Anti-Obesity Agents; Drug Approval; Drug Interactions; Humans; Lactones; Meta-Analysis as Topic; Nonprescription Drugs; Obesity; Orlistat; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration

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

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

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

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

Obesity prevalence is growing as well as its severity with increasing morbidity and mortality. This "globesity" also affects developing countries where under nutrition and stunting frequently coexist with overweight and obesity. One third of obese adults began to be so in the pediatric ages. There are two main types of prevention: general one representing greater actions from health authorities and the individual one carried out by the pediatrician and the patient at risk. Once the state of obesity is reached (relative body mass index, rBMI >121%) the longer lasting care becomes more complex and frequently unsuccessful. The treatment of obesity is aimed to care for the present and silent disorders and for preventing its further tracking to adulthood.. Identification of pediatric population at risk which is the one with an rBMI of 111%-120% plus other risk factors. Specific individual actions include reduction of food intake, increase of energy expenditure, involvement of parents, and the child-adolescent himself in the prevention. Therapy is based on some principles plus the important medical and emotional approach.. A Cochrane study based on only 10 appropriate studies showed a predominant poor efficacy of the undergone preventive action. Treatment guides are presented after our own experience with a group of 400 kids with an average follow-up of 7 years and other individual prevention studies.. Involving motivated pediatricians with a minimum of time for visits and better follow-up in the frame of a general national preventive programme could be a rational outcome. Treatment of obesity should never be postponed whatever the clinical care is.

Topics: Adolescent; Anti-Obesity Agents; Child; Child, Preschool; Comorbidity; Fatty Liver; Feeding Behavior; Female; Humans; Infant; Lactones; Male; Motor Activity; Obesity; Orlistat; Pediatrics; Physician's Role; Socioeconomic Factors

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

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

Weight loss is associated with improvements in glycaemic control and cardiovascular disease risk factors. However, in the diabetic population, weight management is more challenging, in part because of the weight-promoting effects of the majority of glucose-lowering therapies. This review summarizes evidence from 23 placebo-controlled randomized trials, of at least 1 year duration, on the effects of drugs promoting weight loss (orlistat, sibutramine and rimonabant) on glycaemic variables, diabetes incidence and diabetes control. Fifteen studies of non-diabetic subjects were found, eight of which included a longer treatment period. Eight studies in diabetic patients were reviewed. In non-diabetic subjects, weight loss agents led to a significant improvement in fasting glucose, fasting insulin and insulin resistance. In the diabetic population, glycated haemoglobin decreased by 0.28-1.1% with orlistat and 0.6% with sibutramine and rimonabant. Orlistat reduces progression to diabetes in patients with glucose intolerance treated for 4 years (risk reduction of 45%). In summary, despite leading to only modest weight loss after 12 months, agents promoting weight loss have beneficial effects on glycaemic parameters, glycaemic control and progression to diabetes. These additional benefits of weight loss agents need to be highlighted in order to increase their judicious use in clinical practice, although this may be limited by their well-known adverse side effects. The longer-term safety of these agents beyond a few years is yet to be established.

Topics: Adult; Anti-Obesity Agents; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Disease Progression; Glycated Hemoglobin; Humans; Insulin; Lactones; Middle Aged; Obesity; Orlistat; Randomized Controlled Trials as Topic

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

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

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

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

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

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

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

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

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

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

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

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

At any one time large numbers of people are attempting to control their weight. Women are the principal consumers of weight-control programs. Their options, outside the prescription drug market and surgical treatment, include diets and diet books, exercise alone or with supervision in exercise facilities, dietary supplements, group programs, doctors, dietitians, psychologists, and other health-care professionals. Non-prescription products available to help people control their weight cover a wide range, including herbal dietary supplements, diet drinks and portion-controlled foods, meal replacements, and low-carbohydrate diets and foods. The introduction of orlistat as an over-the-counter (OTC) product will provide the only Food and Drug Administration (FDA)-approved product for weight loss currently in that category since phenylpropanolamine (PPA) was withdrawn by the FDA. The FDA approval process is considerably more expensive than allowing untested herbal supplements to be marketed without testing, but the added safety evaluation by the FDA will reduce the risk of disastrous outcomes that have plagued many approaches to weight control. Support for a place for orlistat as an OTC product includes the inadequacy of current programs, empowerment of the public, lower cost, and bringing pharmacists into weight-control programs. The downside includes improper use of OTC orlistat that may not result in achieving individual expectations.

Topics: Anti-Obesity Agents; Body Image; Body Weight; Books; Chronic Disease; Delivery of Health Care; Diet, Carbohydrate-Restricted; Drug Approval; Female; Food, Formulated; Humans; Lactones; Life Expectancy; Male; Nonprescription Drugs; Obesity; Orlistat; Plant Preparations; Prejudice; Quality of Life; Recurrence; Treatment Outcome; United States; United States Food and Drug Administration

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

Rates of pediatric obesity have increased dramatically over the past decade. This trend is especially alarming because obesity is associated with significant medical and psychosocial consequences. It may contribute to cardiovascular, metabolic, and hepatic complications, as well as to psychiatric difficulties. The development of obesity appears to be influenced by a complex array of genetic, metabolic, and neural frameworks, along with behavior, eating habits, and physical activity. Numerous parallels exist between obesity and addictive behaviors, including genetic predisposition, personality, environmental risk factors, and common neurobiological pathways in the brain. Typical treatments for pediatric obesity include behavioral interventions targeting diet or exercise. These treatments have yielded mixed results and typically have been examined in specialty clinic populations, limiting their generalizability. There are limited medication options for overweight children and adolescents, and no approved medical intervention in children younger than 16 years old. Bariatric surgery may be an option for some adolescents, but due to the risks of surgery, it is often seen as a last resort. The parallels between addiction and obesity aid in developing novel interventions for pediatric obesity. Motivational enhancement and cognitive-behavioral strategies used in addiction treatment may prove to be beneficial.

Topics: Adolescent; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Behavior Therapy; Child; Cognitive Behavioral Therapy; Cross-Sectional Studies; Diet, Reducing; Exercise; Humans; Hypoglycemic Agents; Lactones; Metformin; Motivation; Obesity; Orlistat; Prognosis; Risk Factors; Substance-Related Disorders

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Orlistat, in the 60-mg over-the-counter dose, was recently approved by the FDA. This lipase inhibitor blocks absorption of ~25% of ingested fat and has ~85% of the efficacy of the 120-mg dose for weight loss. Over 16 weeks weight loss with diet and orlistat 60 mg averages ~5% of initial body weight. The 60-mg dose is better tolerated than the 120-mg dose and the gastrointestinal side effects are minimal when individuals consume < 30% of their energy from fat. In addition to facilitating modest weight loss, orlistat use decreases serum LDL-cholesterol values by ~10%. When taken three times daily before meals, orlistat 60 mg modifies lifestyle behavior, encourages lower fat-consumption and sets the stage for other healthy lifestyle changes.

Topics: Animals; Body Weight; Dosage Forms; Humans; Lactones; Nonprescription Drugs; Obesity; Orlistat; Overweight

The obesity epidemic is associated with numerous health-related sequelae, including alterations in glucose metabolism, dyslipidemia, and hypertension. These conditions, in turn, are associated with an increased incidence of type 2 diabetes mellitus and cardiovascular disease, which ultimately leads to increased morbidity and mortality. Abdominal obesity, in particular, has been identified as a key risk factor. Accordingly, therapeutic lifestyle change remains the cornerstone of treatment for patients with obesity. Therapeutic lifestyle change is effective; even moderate weight loss leads to clinical improvements. However, lifestyle change is often challenging to implement, and pharmacologic therapies may become necessary. Available pharmacologic and surgical treatment modalities for patients with obesity are fraught with challenges of their own, including poor patient adherence and presence of adverse events. The author outlines available modes of treatment and their consequences for patients with obesity.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Intra-Abdominal Fat; Lactones; Life Style; Metabolic Syndrome; Obesity; Orlistat; Risk Factors

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

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

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

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

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

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

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

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

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

To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.. Updated meta-analysis of randomised trials.. Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006.. Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.. 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.. Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

Topics: Anti-Obesity Agents; Double-Blind Method; Humans; Lactones; Long-Term Care; Obesity; Orlistat; Overweight; Randomized Controlled Trials as Topic

Topics: Anti-Obesity Agents; Body Weight; Cardiovascular Diseases; Humans; Lactones; Obesity; Orlistat; Risk Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Orlistat, a pancreatic lipase inhibitor, was approved by the US Food and Drug Administration (FDA) in the spring of 1999 as an adjunct to lifestyle intervention for weight loss. This paper seeks to examine current issues regarding orlistat use in patients with type 2 diabetes. There are a number of trials that demonstrate the benefits of orlistat over placebo for reducing body weight and improving other health parameters. Of some interest are the preliminary explorations of interaction on cytokine levels, where a possible cardiovascular benefit is plausible. Implications of the FDA approval of over-the-counter use and the pharmaceutical development of another lipase inhibitor are also examined.

Topics: Anti-Obesity Agents; Cytokines; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat; Treatment Outcome

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

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

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

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

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

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

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

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

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

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 inhibitor of gastrointestinal lipases and, therefore, prevents the absorption of dietary fat. This agent reduced weight in obese adults and adolescents with or without co-morbidities (including type 2 diabetes mellitus, hypercholesterolemia, hypertension, metabolic syndrome) who received up to 4 years of therapy in conjunction with a hypocaloric diet. In obese patients, orlistat in combination with a hypocaloric diet improved metabolic risk factors and reduced the risk of developing type 2 diabetes. Furthermore, this agent was cost effective in patients with obesity, particularly those with type 2 diabetes. Orlistat is generally well tolerated, with gastrointestinal adverse events being most commonly reported. Orlistat, in addition to lifestyle and dietary intervention, is thus an attractive option for the treatment of patients with obesity, especially those with associated co-morbidities or at risk of developing type 2 diabetes.

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

The overweight and obesity represent severe problems for the health management system of developed countries. In the evolution of obesity, beside genetic background, the environmental factors also play important roles. In the daily routine, the majority of obese patients need drug treatment, over the diet and physical activity. Among the available medicines the inhibitors of monoamine re-uptake causes dry mouth, tachycardia, sleeplessness and elevated blood pressure, therefore, due to the frequently associated obesity and hypertension many physicians avoid using these compounds. The orlistat as a selective inhibitor of pancreatic and enteral lipase enzymes impedes the absorption of the highest calorie containing nutrients, the fats exerting beneficial effects in the treatment of obesity. The abdominal bloating and diarrhea as side effects of the drug may act as an advantage in many cases, since these happen especially in those cases when the patient neglects the previously suggested low fat diet and therefore the drug induced diarrhea and bloating may mean a feed-back for the patient in respect of the proper diet. Recent studies show many beneficial biochemical changes in obesity related pathological metabolic processes during the administration of orlistat. The authors, in their present work review in short the role of orlistat in the treatment of slimming cure.

Topics: Anti-Obesity Agents; Humans; Intestinal Absorption; Lactones; Lipase; Obesity; Orlistat; Pancrelipase

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

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

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

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

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

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

Changes in the human environment and in human behavior and lifestyle, in conjunction with genetic susceptibility, have resulted in a dramatic increase in the incidence and prevalence of diabetes in the world. The rapid escalation of the number of people with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease demands urgent action on prevention. The Finnish Diabetes Prevention Study and The Diabetes Prevention Program showed that the prevention (or delaying) of T2DM is feasible and effective. Both of these trials led to a reduction of 58% in the conversion to diabetes in subjects with impaired glucose tolerance. Compared to lifestyle changes, drug treatment in the prevention of diabetes in people at high risk for T2DM has been less beneficial. Metformin (31%) or acarbose (25%) treatment obtained only about a half of the reduction in the conversion to diabetes compared to lifestyle changes. These drugs require monitoring, and have significant side-effects. Also the effect of orlistat (37%) did not reach the effect of lifestyle modification. Results of the Troglitazone in Prevention of Diabetes study are suggestive for the prevention, but the trial was too small, and included only one ethnic group (Hispanic) and one gender (women). On the basis of the evidence available, we do not have a definite proof that T2DM is prevented in any of these trials. However, we can safely conclude that the current evidence strongly favors the notion that lifestyle changes are the primary means to tackle the epidemic of T2DM.

Topics: Acarbose; Birth Weight; Blood Glucose; Chromans; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Environment; Exercise; Female; Finland; Humans; Hypertension; Lactones; Life Style; Male; Obesity; Orlistat; Risk Factors; Thiazolidinediones; Time Factors; Troglitazone

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

The need for an effective and safe medical treatment of nonalcoholic fatty liver disease is urgent due to its high prevalence and progressive character. At the moment, therapeutic strategies are largely empirical and based on the control of associated clinical conditions (especially obesity, type 2 diabetes mellitus, and hypertriglyceridemia) and the use of some specific drugs (insulin sensitizing agents, cytoprotectives, antioxidants, and anticytokines) as an attempt to counteract known elements of the pathogenesis. None of these specifics measures have been found to display enough evidence to recommend their clinical use. It is indispensable to join efforts in coordinated networks to define, as soon as possible, the best treatment and the best time to start it.

Topics: Anti-Obesity Agents; Anticholesteremic Agents; Atorvastatin; Chromans; Diabetes Mellitus, Type 2; Fatty Liver; Heptanoic Acids; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Metabolic Syndrome; Metformin; Obesity; Orlistat; Prevalence; Pyrroles; Rosiglitazone; Thiazolidinediones; Troglitazone

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

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

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

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

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

To 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

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

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

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

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

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

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

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

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

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

Topics: Anti-Obesity Agents; China; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise Therapy; Finland; Humans; Lactones; Life Style; Obesity; Orlistat; Primary Prevention; Prospective Studies; Risk Factors; Sweden; Treatment Outcome; United States

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

Topics: Anti-Obesity Agents; Dietary Fats; Digestion; Enzyme Inhibitors; Humans; Lactones; Lipase; Lipid Metabolism; Obesity; Orlistat

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

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

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

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

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

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

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

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

Orlistat is an inhibitor of gastrointestinal lipases and, therefore, prevents the absorption of dietary fat. This agent reduces weight in obese adults and adolescents with or without comorbidities (including type 2 diabetes mellitus, hypercholesterolaemia, hypertension, metabolic syndrome) who received up to 4 years of therapy in conjunction with a hypocaloric diet. In obese patients, orlistat in combination with a hypocaloric diet improved metabolic risk factors and reduced the risk of developing type 2 diabetes. Furthermore, this agent was cost effective in patients with obesity, particularly those with type 2 diabetes. Orlistat is generally well tolerated, with gastrointestinal adverse events being most commonly reported. Orlistat, in addition to lifestyle and dietary intervention, is thus an attractive option for the treatment of patients with obesity, especially those with associated comorbidities or at risk of developing type 2 diabetes.

Topics: Anti-Obesity Agents; Caloric Restriction; Diabetes Mellitus, Type 2; Humans; Lactones; Metabolic Syndrome; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Orlistat has been well studied in several populations, including patients who do and do not have type 2 diabetes and in patients who have impaired glucose tolerance. Overall, modest, but significant, weight loss was seen in all three groups of patients with favorable effects on the comorbidities of obesity. Orlistat has not been associated with a serious adverse event profile, and the mild GI effects that are seen in some patients are well tolerated. In obese patients who do not have diabetes, weight loss is achieved and maintained as shown in the 2-year studies. Moreover, as was well documented in the Swedish multi-morbidity study, favorable treatment effects on the constituents of the metabolic syndrome are seen. Orlistat, together with a hypocaloric diet, was proven to be effective in preventing diabetes in patients who had impaired glucose tolerance. The addition of orlistat resulted in significant weight loss and significance decreases in levels of HbA1c in patients who had type 2 diabetes who were treated with antihyperglycemic drugs. Studies showed that it is possible to identify early which patients may respond best to treatment. Orlistat offers an attractive treatment option for obese patients who do and do not have diabetes and as a combination drug for treatment of obese patients who have type 2 diabetes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Adrenergic Agonists; Anti-Obesity Agents; Behavior Therapy; Diabetes Mellitus; Diet, Reducing; Enzyme Inhibitors; Exercise Therapy; Gastric Bypass; Humans; Hypoglycemic Agents; Lactones; Lipase; Obesity; Orlistat; Serotonin Receptor Agonists

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

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

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

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

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

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

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

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

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

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

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

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

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

Orlistat is a non-centrally acting anti-obesity agent that acts locally in the gastrointestinal tract to inhibit lipase, an enzyme that is crucial for the digestion of long-chain triglycerides. At the recommended dose of 120 mg three times daily, orlistat inhibits dietary fat absorption by about 30%. Over a 1-year period, obese patients taking orlistat in combination with a hypocaloric diet show a reduction of 2-5 kg over the weight decrease with placebo. When continued for a second year in combination with a weight maintenance diet, orlistat reduces weight regain compared to placebo-treated patients. Orlistat in combination with dietary intervention is also associated with beneficial effects on cardiovascular risk factors including total and low-density lipoprotein cholesterol, blood pressure and plasma glucose. It is not known if orlistat has any impact on clinical outcomes such as myocardial infarction, stroke and sudden death. Orlistat has not been compared with other anti-obesity agents.

Topics: Animals; Anti-Obesity Agents; Blood Pressure; Body Weight; Cholesterol, LDL; Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Lactones; Obesity; Orlistat

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

To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of obesity.. English-language articles were identified from MEDLINE (1966-July 2000), Roche Laboratories, organizational guidelines, National Institutes of Health and Food and Drug Administration Web sites, and Doctor's Guide online. Key words included obesity, orlistat, and lipase inhibitors. References were also identified from reference sections of published articles.. Prospective, randomized, double-blind, placebo-controlled, human trials were selected for review and discussion.. Orlistat is the first agent in the lipase inhibitor class of antiobesity drugs. Orlistat is minimally absorbed and has been shown to reduce body weight by inhibiting absorption (by approximately 30%) of ingested dietary fat. Safety and efficacy have been established in one- and two-year double-blind, placebo-controlled trials; adverse effects were primarily, and almost exclusively, gastrointestinal. Due to its ability to block fat absorption, orlistat also has the capability to inhibit absorption of fat-soluble vitamins. Therefore, a daily multiple vitamin is recommended while taking orlistat.. By inhibiting fat absorption, orlistat offers a new treatment modality for weight loss and maintenance. Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia. However, further studies during postmarketing surveillance are needed to fully establish orlistats long-term benefits and safety. Orlistat should be considered a useful adjunctive therapy for weight loss and maintenance in obese patients (i.e., body mass index > or = 30 kg/m2 or > or = 27 kg/m2 if other risk factors are present) committed to lifestyle changes including diet, exercise, and behavioral modification.

Topics: Animals; Anti-Obesity Agents; Clinical Trials as Topic; Humans; Lactones; Obesity; Orlistat

Topics: Advertising; Anti-Obesity Agents; Canada; Decision Making, Organizational; Drug Industry; Drug Prescriptions; Erectile Dysfunction; Female; Health Care Rationing; Humans; Lactones; Life Style; Male; National Health Programs; Obesity; Orlistat; Patient Selection; Phosphodiesterase Inhibitors; Piperazines; Practice Patterns, Physicians'; Purines; Sildenafil Citrate; Sulfones

The prevalence of obesity in developed societies is increasing. Obesity is associated with an increased risk of co-morbidity, including cardiovascular disease and diabetes. Following the withdrawal of fenfluramine and dexfenfluramine, interest has focused on a novel anti-obesity drug orlistat.. To systematically assess the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity. METHODS - SEARCH STRATEGY: Nineteen electronic databases were searched from inception to June 2000. Additionally, Internet searches were carried out, bibliographies of retrieved articles were examined and submissions were received from the manufacturer of orlistat. METHODS - INCLUSION AND EXCLUSION CRITERIA: Randomised controlled trials (RCTs) evaluating the effectiveness of orlistat used for weight loss or maintenance of weight loss in overweight or obese patients were eligible for inclusion. Primary outcome measures were changes in body weight, fat content or fat distribution. Secondary outcomes were changes in obesity-related risk-factor profiles, such as lipid levels, indicators of glycaemic control and blood pressure. Studies recruiting people with eating disorders such as anorexia nervosa and bulimia nervosa were excluded. METHODS - PROCESS OF STUDY SELECTION: Assessment of titles and abstracts was performed independently by two reviewers. If either reviewer considered a reference to be relevant, the full paper was retrieved. Full papers were assessed against the review selection criteria by two independent reviewers, and disagreements were resolved through discussion. METHODS - DATA EXTRACTION: Data were extracted by one reviewer into structured summary tables and checked by a second reviewer. Any disagreements about data were resolved by discussion. METHODS - QUALITY ASSESSMENT: Each included trial was assessed against a comprehensive checklist for methodological quality. Quality assessment was performed independently by two reviewers with disagreements resolved by discussion. METHODS - METHODS OF ANALYSIS/SYNTHESIS: This report is a narrative summary, with results grouped according to study endpoint. Statistical pooling was undertaken in groups of trials that were considered to be sufficiently similar. METHODS - ESTIMATION OF QUALITY OF LIFE, COSTS AND COST-EFFECTIVENESS AND/OR COST PER QUALITY-ADJUSTED LIFE-YEAR: Relevant economic evaluations were identified from the search strategy described above. Assessment of methodological quality was undertaken using principles outlined in published guidelines. METHODS - COMPANY SUBMISSIONS: Data from company submissions were subject to the same selection and appraisal processes as other studies considered for inclusion in the review, except that only RCTs with a duration of at least 1 year

Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Drug Evaluation; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Technology Assessment, Biomedical; Treatment Outcome; United Kingdom

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

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

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

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

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

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

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

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

There are two types of anti-obesity agents which are classified as inhibitors of absorption: inhibitors of lipid and carbohydrate absorption. Inhibitors of lipid absorption consist of lipase inhibitor (orlistat, Nomma Herb's extract (CT-II) and fat substitute (olestra, sucrose polyester). Orlistat is now available as an anti-obesity drug in the USA and Europe. CT-II may be useful as a functional diet. Application of fat substitute is still limited in snack food. As for inhibitors of carbohydrate absorption, alpha-glucosidase inhibitors are now available as anti-diabetic drugs. To develop these agents for anti-obesity drug, solution of adverse effects on the gastrointestinal tract are necessary.

Topics: Carbohydrate Metabolism; Glycoside Hydrolase Inhibitors; Humans; Intestinal Absorption; Lactones; Lipid Metabolism; Obesity; Orlistat

Orlistat is a nonsystemically acting gastric and pancreatic lipase inhibitor that limits the absorption of dietary fat. A retrospective pooled analysis of three 2-year, double-blind, randomised, placebo-controlled trials involving patients with obesity revealed that orlistat recipients were more likely to experience an improvement, and less likely to experience a deterioration, in glucose tolerance status than placebo recipients. In comparison with placebo, orlistat recipients had significantly greater reductions in glycosylated haemoglobin and fasting plasma glucose levels in large, double-blind, randomised, placebo-controlled studies of 24 to 52 weeks' duration involving patients with obesity and type 2 diabetes mellitus. In one such study, the dosage of concomitant sulphonylureas was able to be reduced in more orlistat than placebo recipients (43.2 vs 28.9%), with discontinuation of sulphonylurea therapy achieved in 11.7% of orlistat recipients. The most common adverse effects reported in orlistat recipients with type 2 diabetes mellitus relate to the gastrointestinal system and are similar to those reported in studies involving patients without type 2 diabetes mellitus.

Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Treatment Outcome

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

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

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

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

The aim of this study is to clarify the potential benefits, disbenefits and costs of Orlistat for the treatment of obesity. The method was a search for relevant systematic reviews and randomized controlled trials, in Medline, Pre-Medline, Embase and the Cochrane Library, using Orlistat and its synonyms. Identified trials were appraised using a standard appraisal checklist and trial data were extracted for use in cost-effectiveness modelling. Three large multicentre, randomized placebo controlled trials were included in the rapid review. On average, Orlistat results in obese people losing an additional 3-4% of their initial body weight over diet alone during a 2 year period. There was no strong evidence that this short-term weight loss would have a longer-term impact on morbidity and mortality. The cost utility of Orlistat treatment was estimated at around 46,000 Pounds per Quality Adjusted Life Year gained (extreme values sensitivity analysis 14,000 Pounds to 132,000 Pounds). This rapid review raises some important questions about the potential value of Orlistat in the treatment of obesity. Further research is needed, not only to clarify the longer-term impact of Orlistat treatment, but also to uncover the longer-term impact on mortality and morbidity from short-term weight loss.

Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Humans; Lactones; Obesity; Orlistat; Quality of Life; Randomized Controlled Trials as Topic

Orlistat, a weight-loss agent with a novel mechanism of action, recently was approved by the Food and Drug Administration for the treatment of obesity. It inhibits gastric and pancreatic lipases in the lumen of the gastrointestinal tract to decrease systemic absorption of dietary fat. In several trials lasting up to 2 years, orlistat was more effective than diet alone for weight reduction and maintenance of lost weight. Orlistat treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and insulin concentrations. The major adverse effects are gastrointestinal, usually occur early in therapy, and tend to decrease with continued treatment. Because orlistat may decrease the absorption of fat-soluble vitamins, a standard multiple-vitamin supplement is recommended daily during therapy to prevent abnormalities in vitamin serum concentrations. The potential for severe gastrointestinal discomfort and the modest degree of weight loss may limit the agent's clinical utility. Its long-term safety and effectiveness for weight maintenance, cost-effectiveness of treatment, and overall reduction in obesity-related morbidity and mortality remain to be determined.

Topics: Anti-Obesity Agents; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat; Randomized Controlled Trials as Topic

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

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

Obesity is worldwide one of today's most important medical and public health problems. Orlistat (Xenical) is a relatively new drug in the pharmacological treatment of obesity which partially blocks fat absorption. The following article analyses the available evidence of orlistat's effectiveness in the treatment of obese patients.. Three randomised controlled trials investigating the effect of orlistat in the treatment of obesity were identified by systematic Medline search. The internal and external validity of these studies was assessed using systematic criteria.. All three studies consistently demonstrate a treatment benefit of orlistat compared to placebo. Patients treated with orlistat lost an average of 3.4 kg more than patients taking placebo while on a hypocaloric diet. Simultaneously, control of cardiovascular risk factors improved independently of the observed weight loss. Up to 40% of all patients experienced gastrointestinal side effects which were generally well tolerated. The studies prove that treatment with orlistat can result in a moderate weight reduction. However, the results of the studies cannot be easily generalised to obese patients in a primary care setting, due to limitations concerning the studies' internal and external validity.. Based on these studies orlistat is an efficient pharmacological treatment for obesity in patients adhering to a hypocaloric diet. Studies demonstrating orlistat's effectiveness in a primary care setting are so far lacking. From a public health perspective there is a need for a randomised controlled trial showing not only orlistat's effectiveness on surrogate markers in a primary care setting but, ideally, a reduction in obesity-related mortality and morbidity.

Topics: Anti-Obesity Agents; Diet, Reducing; Humans; Lactones; MEDLINE; Obesity; Orlistat; Randomized Controlled Trials as Topic

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

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

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

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

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

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

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

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

Topics: Anti-Obesity Agents; Behavior Therapy; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Energy Intake; Energy Metabolism; Exercise; Humans; Lactones; Lipase; Obesity; Orlistat; Treatment Outcome

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

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

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

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

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

Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Orlistat is indicated for patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the presence of obesity-associated complications, such as hypertension, diabetes mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials, orlistat (120 mg t.i.d.) in combination with life-style modification and a hypocaloric diet (30% of energy from fat) induced significantly more weight loss and improved health complications of obesity (diabetes, hypertension, hyperlipidaemia) compared to patients treated with diet alone. Side effects related to fat malabsorption, occurred in more than 20% of subjects during the first year of treatment and included oily faecal spotting, abdominal pain, flatus with discharge and fatty/oily stool. Side effects from orlistat diminished in the second year of treatment. Plasma concentrations of fat soluble vitamins decreased in orlistat-treated patients but did not usually fall below the normal range. No studies have evaluated the efficacy of orlistat or side effect profile beyond two years.

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Drug Interactions; Humans; Lactones; Obesity; Orlistat

Topics: Adrenergic Agents; Animals; Appetite Depressants; Fatty Acids; Humans; Lactones; Leptin; Lipase; Obesity; Orlistat; Serotonin Agents; Sucrose

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

Obesity is a major health problem in western societies. The mainstay of therapy is behavioral modification. By inhibiting intestinal lipases orlistat modifies food composition. Thus, orlistat is a dietetic compound. Therefore, orlistat does not represent a medically necessary treatment option in terms of the conditions of private health insurances. However, adjunctive treatment with orlistat may make sense in single high risk patients.

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

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

Topics: Acromegaly; Anti-Obesity Agents; Female; Growth Hormone; Humans; Lactones; Obesity; Octreotide; Orlistat; Osteoporosis, Postmenopausal

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 obesity has doubled in the last 10 years and is now reaching epidemic proportions. There is a significant comorbidity and financial cost associated with this disorder. Orlistat is an intestinal lipase inhibitor that is approved for the treatment of obesity. Recent randomized, double-blind, placebo-controlled trials have demonstrated the benefit of orlistat used in conjunction with a hypocaloric (low-fat) diet in facilitating weight reduction and the long-term maintenance of this weight loss. Patients treated with orlistat lost a greater amount of initial body weight compared to those who received placebo. After 24 months of treatment, weight loss of more than 5% was maintained in a greater number of those treated with orlistat. This was associated with significant reductions in cardiovascular risk factors (cholesterol, LDL cholesterol, LDL:HDL cholesterol ratio). The main adverse events are related to fat malabsorption, with potential losses of fat-soluble vitamins and other compounds. Orlistat as a treatment for obesity, when prescribed within present guidelines, can aid modest weight loss in about one-third of patients. More importantly, it can assist in the maintenance of weight loss with major medical benefits for these patients.

Topics: Anti-Obesity Agents; Humans; Lactones; Nutrition Disorders; Obesity; Orlistat

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

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

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

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

Orlistat is a novel non-systemic treatment for obesity. The drug inhibits lipases in the gastrointestinal tract, preventing the absorption of approximately 30% of dietary fat. Pharmacodynamic and dose-finding studies have established that a 120 mg dose of orlistat 3 times daily (with each main meal) is optimal. Controlled studies have established that orlistat 120 mg 3 times daily for 1 year, in conjunction with a hypocaloric diet, enables weight reduction of 7.9 to 10.2% in obese non-diabetic individuals. In 1 study the reduction was 6.2% in obese patients with type 2 diabetes. Orlistat 120 mg 3 times daily was significantly more effective than placebo (also given in conjunction with a hypocaloric diet) in these studies. The drug was also significantly more effective than placebo in 2-year randomised double-blind studies involving >2000 patients. During the second year of treatment, when patients were switched from a hypocaloric diet to a eucaloric diet, orlistat recipients regained significantly less weight than placebo recipients. Orlistat appears to improve lipid profiles in non-diabetic obese patients, reducing levels of total cholesterol and low density lipoprotein cholesterol. In a study of patients with obesity associated with type 2 diabetes, patients treated with orlistat lost more weight and had improved serum lipid profiles compared with placebo recipients. In addition, orlistat-treated patients achieved significant improvements in glycaemic control, enabling dosages of antidiabetic drugs to be reduced. Long term (1 to 2 years) tolerability data from 2038 patients in placebo-controlled trials revealed that the drug was generally well tolerated. The most commonly reported adverse events were related to decreased fat absorption and included oily faecal spotting, flatus with discharge, faecal urgency and oily stool. Systemic adverse events attributable to orlistat were negligible.. Orlistat in conjunction with a hypocaloric diet has been shown to induce clinically significant weight loss in keeping with current guidelines for the management of obesity. This, together with its acceptable tolerability profile and lack of systemic adverse events, make it an attractive option in the treatment of obesity. The drug may have a positive effect on obesity-associated cardiovascular risk factors and type 2 diabetes.

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

Topics: Anti-Obesity Agents; Cholesterol; Dietary Fats; Homeostasis; Humans; Hypercholesterolemia; Intestinal Absorption; Lactones; Obesity; Orlistat; Triglycerides

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

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Enzyme Inhibitors; Lactones; Lipase; Obesity; Orlistat

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: Anti-Obesity Agents; Diet, Reducing; Humans; Lactones; Obesity; Orlistat; Patient Care Team; Public Health; United Kingdom

The introduction of orlistat (Roche, UK) at the end of last year received considerable media coverage and was heralded in some quarters as the 'quick fix' for those wishing to lose weight without the pain of dieting. This description is far from accurate but treatment with orlistat may have a role in patients for whom obesity is a serious and even life-threatening condition.

Topics: Anti-Obesity Agents; Drug Monitoring; Drug Prescriptions; Humans; Lactones; Obesity; Orlistat; Patient Selection

Drugs to treat obesity can be divided into three groups: those which reduce food intake, those which alter metabolism and those which increase thermogenesis. Monoamines acting on noradrenergic receptors, serotonin receptors, dopamine receptors and histamine receptors can reduce food intake. A number of peptides also affect food intake. The noradrenergic drugs phentermine, diethylpropion, mazindol benzphetamine and phendimetrazine are approved only for short-term use. Sibutramine, a norepinephrine-serotonin re-uptake inhibitor, is approved for long-term use. Orlistat inhibits pancreatic lipase and can block 30% of triglyceride hydrolysis in subjects eating a 30% fat diet. The only thermogenic drug combination that has been tested is ephedrine and caffeine, but this treatment has not been approved by regulating agencies. Leptin is currently in clinical trials and other drugs that may modulate peptide-feeding systems are being developed.

Topics: Androgen Antagonists; Androgens; Anti-Obesity Agents; Appetite Depressants; Caffeine; Central Nervous System Stimulants; Energy Metabolism; Enzyme Inhibitors; Ephedrine; Humans; Hypoglycemic Agents; Lactones; Lipase; Metformin; Obesity; Orlistat; Patient Selection

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

Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.

Topics: Drug Tolerance; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat

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

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

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

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

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

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

This review explains and surveys very recent findings and experimental results concerning molecular pathology and genetics of overweight and obesity and also evaluates their relevance for the actual treatment of obesity at present. Most of these studies were done on inbred obese mice or rats and it is yet unknown to what extent the results do apply to human overweight. Nevertheless these studies led to the discovery of a new hormone--OB-protein or leptin--produced by adipocytes of animals. It does not only increase satiety by influencing feeding centers and decrease body weight but it also interferes with several peripheral metabolic functions. Mutations of leptin expression or expression of leptin receptors as observed in animals are, however, very rare in humans. In obese individuals (and animals) there is a yet unexplained resistance to the effects of leptin which interferes with successful therapeutic use of leptin in human obesity. Various other recently discovered transmitters modifying feeding habits may, however, become targets of future drugs making dietary weight loss and its maintenance more acceptable and successful. At present obese people and patients have to rely, however, on traditional methods of weight loss though these are known to yield poor results over prolonged periods of time. Orlistat, a recently introduced drug results in malabsorption of fat from the gut by inhibiting lipases. Though it is not based on recent insights to regulation of body weight it is promising primarily for educating patients to reduce their nutritional fat intake.

Topics: Animals; Appetite; Carrier Proteins; Enzyme Inhibitors; Gene Expression; Humans; Lactones; Leptin; Lipase; Mice; Mice, Obese; Mutation; Obesity; Orlistat; Proteins; Rats; Receptors, Cell Surface; Receptors, Leptin

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

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

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

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

Several brain receptor systems can modulate food intake. Thus, in a new strategy against obesity, the patient takes submaximal doses of two drugs that act by differing mechanisms.

Topics: Adrenergic beta-Agonists; Appetite Depressants; Attitude to Health; Ethanolamines; Growth Hormone; Humans; Lactones; Lipase; Obesity; Orlistat; Recurrence; Testosterone; Treatment Failure

Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance.. This study aimed to compare the effects of orlistat or an experimental high-protein/lower-carbohydrate diet with a control diet in Asian patients with obesity and MAFLD.. A total of 118 Asian patients with obesity and MAFLD confirmed with MRI-based proton density fat fraction with Dixon sequence were enrolled and allocated to the control group, the orlistat group, or the experimental diet group for 24 wk. The primary endpoint was the relative change in liver fat content (LFC) assessed by MRI-based proton density fat fraction.. A total of 118 subjects with obesity and MAFLD were randomly assigned to the control group (n = 39), the orlistat group (n = 40), or the experimental diet group (n = 39). All 3 groups demonstrated improvement in liver steatosis at wk 24. The absolute decrease in LFC in the orlistat group was 9.1% and 5.4% in the experimental diet group, both significantly higher than that in the control group (P < 0.05). The relative reduction in LFC was 30.2% in the experimental diet group, which was significantly higher than the 12.2% observed in the control group (P = 0.01).. Orlistat and the experimental diet group reduced liver steatosis compared to the control group. This trial was registered at Chinese Clinical Trial Registry (ChiCTR-1900027172). http://www.chictr.org.cn.

Topics: Anti-Obesity Agents; Diet; Fatty Liver; Humans; Lactones; Liver Diseases; Obesity; Orlistat; Protons

To investigate the effects of an orlistat mouth rinse on the intake of a high-fat meal.. The orlistat mouth rinse decreased total and fat calories consumed during the high-fat meal in high-fat consumers, and did not alter calories consumed in low-fat consumers (P < 0.05).. Orlistat decreases long-chain fatty acid (LCFA) absorption by inhibiting lipases that breakdown triglycerides. Orlistat mouth rinse decreased fat intake in high-fat consumers, suggesting that orlistat inhibited the detection of LCFAs from the high-fat test meal. Lingual delivery of orlistat is predicted to eliminate the risk of oil incontinence and promote weight loss in individuals who prefer fat.

Topics: Anti-Obesity Agents; Cross-Over Studies; Double-Blind Method; Humans; Lactones; Mouthwashes; Obesity; Orlistat; Pilot Projects

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

Topics: Body Mass Index; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome

Obesity management prior to infertility treatment remains a challenge. To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no evidence of improved live birth rate.. This work aimed to determine whether pharmacologic weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women.. We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25 or greater were randomly assigned to receive orlistat (n = 439) or placebo (n = 438) treatment for 4 to 12 weeks. The main outcome measurement was the live birth rate after fresh ET.. The live birth rate was not significantly different between the 2 groups (112 of 439 [25.5%] with orlistat and 112 of 438 [25.6%] with placebo; P = .984). No significant differences existed between the groups as to the rates of conception, clinical pregnancy, or pregnancy loss. A statistically significant increase in singleton birth weight was observed after orlistat treatment (3487.50 g vs 3285.17 g in the placebo group; P = .039). The mean change in body weight during the intervention was -2.49 kg in the orlistat group, as compared to -1.22 kg in the placebo group, with a significant difference (P = .005).. Orlistat treatment, prior to IVF-ET, did not improve the live birth rate among overweight or obese women, although it was beneficial for weight reduction.

Topics: Adult; Anti-Obesity Agents; Birth Rate; Body Mass Index; Body Weight; China; Double-Blind Method; Embryo Transfer; Female; Fertilization in Vitro; Humans; Infertility, Female; Obesity; Orlistat; Overweight; Pregnancy; Pregnancy Outcome; Sperm Injections, Intracytoplasmic; Treatment Outcome

Orlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat accumulation in Japanese subjects. Therefore, this comparative, placebo-controlled, double-blind, randomized study aimed to evaluate the efficacy and safety of orlistat in Japanese participants with excessive visceral fat accumulation and without dyslipidemia, diabetes mellitus, and hypertension ("metabolic diseases").. The study population included Japanese participants with excessive visceral fat accumulation (waist circumference ≥ 85 cm in males and ≥ 90 cm in females, which corresponds to a visceral fat area of 100 cm. Visceral fat area, waist circumference, and body weight were significantly reduced in the orlistat group (mean ± standard error, - 13.50 ± 1.52%, - 2.51 ± 0.25%, and - 2.79 ± 0.30%, respectively) compared to the placebo group (- 5.45 ± 1.50%, - 1.55 ± 0.26%, and - 1.22 ± 0.28%, respectively) at the last assessment. The main adverse reactions were defecation-related symptoms including oily spotting and flatus with discharge, resulting from the pharmacological effects of orlistat. Most adverse reactions were mild, and none were serious or severe.. Orlistat administration reduced visceral fat area, waist circumference, and body weight in Japanese participants with excessive visceral fat and without metabolic diseases. In addition, safety was confirmed with a tolerable profile. Orlistat may be useful to reduce excessive visceral fat accumulation when used in combination with diet and exercise.. Japan Pharmaceutical Information Center identifier, JapicCTI-184005.. Taisho Pharmaceutical Co., Ltd.

Topics: Adult; Anthropometry; Anti-Obesity Agents; Body Mass Index; Body Weight; Combined Modality Therapy; Double-Blind Method; Exercise; Female; Humans; Intra-Abdominal Fat; Japan; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome

To evaluate the effect of Diane-35, alone or in combination with orlistat or metformin, on androgen and body fat percentage parameters in Chinese overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance.. A total of 240 PCOS women were randomly allocated to receive Diane-35 alone (D group), Diane-35 plus orlistat (DO group), Diane-35 plus metformin (DM group), or Diane-35 plus orlistat plus metformin (DOM group). Serum TT, DHEA-S, androstenedione, SHBG, FT, FAI, body fat, and body fat percentage were assessed at baseline and after 12 weeks of treatment.. Significant changes in serum TT, SHBG, and FAI were observed in all treatment groups compared with baseline. DHEA-S and androstenedione significantly decreased in the DO, DM, and DOM groups after treatment. FT only significantly decreased in the DOM group. Body fat and body fat percentage significantly decreased in the DO and DOM groups. Compared with the D group, DHEA-S significantly decreased in the DO, DM, and DOM groups (F = 4.081, p = 0.008); SHBG significantly increased in the DOM group (F = 3.019, p = 0.031); and FAI significantly decreased in the DO group (χ. Diane-35 in combination with orlistat or metformin is more effective in reducing androgen than Diane-35 alone. Orlistat is more effective in reducing body fat percentage than metformin. In addition, orlistat has mild side-effects and is better tolerated compared with metformin.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Androgens; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Humans; Insulin Resistance; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Treatment Outcome

Obese women have fewer oocytes retrieved, an increased cancelation rate, a higher miscarriage rate, and a lower live birth rate after assisted reproductive technology (ART) treatment compared with women with normal weight. Weight loss before ART treatment can significantly improve pregnancy rates and/or live births. An orlistat plus diet intervention could promote weight loss, but there is no evidence from randomized clinical trials evaluating the effect of orlistat preconceptional treatment on pregnancy outcome in overweight and obese women.. We are conducting a multicenter, randomized placebo-controlled, double-blind clinical trial in overweight and obese women aged 20-40 years undergoing in-vitro fertilization and embryo transfer (IVF-ET) with or without intracytoplasmic sperm injection, to evaluate whether orlistat treatment for 1-3 months before IVF-ET can improve the live birth rate. The primary outcome is live birth.. The results of this study will provide evidence for the effect of preconceptional orlistat treatment on IVF outcome in overweight/obese women.. Chinese Clinical Trial Registry, ChiCTR-IPR-17011629 . Registered on 11 June 2017.

Topics: Adult; Anti-Obesity Agents; China; Double-Blind Method; Drug Administration Schedule; Female; Fertility; Fertilization in Vitro; Humans; Infertility, Female; Live Birth; Multicenter Studies as Topic; Obesity; Orlistat; Preconception Care; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Young Adult

A range of studies showed confusing data about the relationship between obesity, weight reduction and circulating total insulin-like growth factor -1 (IGF-1). The aim of the study was to compare the influence of orlistat (IO), metformin (IM), or calorie-restricted diet (LC) on IGF-1, with special respect to insulin-resistance status. One hundred and fourteen obese women aged from 18 to 40 years were divided into insulin sensitive (IS) and insulin resistant (IR) groups and received a low calorie diet (LC), or an isocaloric diet and 500 mg metformin twice daily (IM), or isocaloric diet with 120 mg orlistat three times daily (IO). Before and after the intervention anthropometric parameters, serum lipid profile, serum concentrations of alanine aminotransferase, aspartate aminotransferase, insulin, glucose, IGF-1, HOMA-IR (homeostatic model assessment), and visceral adiposity index (VAI), and their changes were registered. Although the reductions in weight and body fat were comparable in IS and IR groups, only women with IR showed a significant increase in IGF-1 concentration as a result of all interventions. We found significant positive correlations of ΔIGF-1 with initial and Δ values of: HOMA-IR, triglyceride/high-density cholesterol ratio, VAI. IR premenopausal women show significant increase in IGF-1 serum concentrations regardless the method of intervention. The increase in IGF-1 was parallel to the improvement of insulin resistance parameters.

Topics: Adult; Anti-Obesity Agents; Caloric Restriction; Diet; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin-Like Growth Factor I; Intra-Abdominal Fat; Metformin; Obesity; Orlistat; Premenopause

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

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

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

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

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

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

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

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

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

To investigate the effect of orlistat on endothelial function in obese adolescents.. Single-blind 10-week controlled trial of 67 normolipidaemic obese adolescents randomised into three groups. Group 1 (diet alone), Group 2 (diet and orlistat), Group 3 (diet, orlistat and exercise). Endothelial function measured by flow-mediated dilatation (FMD) of the brachial artery, anthropometric parameters, blood pressure, fasting blood lipids, insulin and glucose levels were recorded at baseline and at 10 weeks.. Sixty four subjects completed the study. Groups were comparable at baseline. FMD increased significantly with orlistat (Groups 2 and 3) but not in Group 1. Orlistat treatment resulted in significantly reduced bodyweight, body mass index (BMI), waist circumference, total and low-density lipoprotein (LDL) cholesterol levels. High-density lipoprotein cholesterol levels were unchanged. Triglyceride and insulin levels were significantly reduced in all three groups. The reduction in cholesterols did not correlate with reductions in weight and BMI. A slight reduction of body fat, both with and without orlistat treatment, correlated with reduction in BMI after adjustment for baseline values. Blood pressure was unaltered by orlistat. Calorie intake was reduced with orlistat, and the decrease noted in % fat and increase in % carbohydrate was significant only in those taking orlistat. The addition of exercise (Group 3 compared with Group 2) altered no parameter.. Orlistat improves endothelial function and reduces bodyweight, BMI, fasting total and LDL-cholesterol in obese adolescents when combined with dietary control. Improvement in endothelial function if maintained could reflect long-term cardiovascular benefit.

Topics: Adolescent; Anthropometry; Anti-Obesity Agents; Blood Pressure Determination; Child; Endothelial Cells; Energy Intake; Fasting; Female; Hong Kong; Humans; Lactones; Male; Motor Activity; Obesity; Orlistat

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

  The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes.. Two hundred and fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360mg or placebo for 1year. We evaluated at baseline and after 3, 6, 9 and 12months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP).. We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat group (r=-0·53, P<0·05, and r=-0·59, P<0·01, respectively).. To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.

Topics: Anti-Obesity Agents; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Inflammation; Insulin Resistance; Lactones; Lipids; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Retinol-Binding Proteins, Plasma

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

To examine whether changes in different aspects of dietary restraint in obese patients with binge eating disorder (BED) participating in a treatment study predict outcomes.. Fifty obese patients with BED in a randomized controlled study of orlistat administered with cognitive-behavioral therapy, guided-self-help (CBTgsh) completed dietary restraint measures at baseline, during- and post-treatment, and three-month follow-up.. Change in the restraint scale of the Eating Disorder Examination-Questionnaire did not predict binge abstinence or 5% weight loss. Increased flexible restraint subscale of the Three Factor Eating Questionnaire (TFEQ) during treatment significantly predicted binge abstinence at post-treatment and three-month follow-up and 5% weight loss at post-treatment. Change in the rigid restraint subscale of the TFEQ predicted binge abstinence at post-treatment.. Our findings clarify further pathologic and adaptive aspects of restraint and suggest the importance of enhancing flexible restraint in order to improve both binge eating and weight loss outcomes.

Topics: Adult; Anti-Obesity Agents; Binge-Eating Disorder; Cognitive Behavioral Therapy; Diet; Feeding Behavior; Female; Follow-Up Studies; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Predictive Value of Tests; Self Care; Surveys and Questionnaires

To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated the following parameters at baseline and after 3, 6, 9, and 12 months: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c) ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), adiponectin (ADN), leptin, tumor necrosis factor-α (TNF-α), vaspin, and high-sensitivity C-reactive protein (Hs-CRP). We observed a better decrease in body weight, glycemic profile, HOMA-IR, LDL-C, and ADN and a faster improvement in FPI, TC, Tg, leptin, TNF-α, Hs-CRP with orlistat plus L-carnitine compared to orlistat alone. We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone. Orlistat plus L-carnitine gave a better improvement in body weight, glycemic and lipid profile compared to orlistat alone; furthermore, a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone.

Topics: Adiponectin; Anti-Inflammatory Agents; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Carnitine; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Lactones; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Obesity; Orlistat; Thiazolidinediones; Time Factors

Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome.. A total of 80 women were prospectively recruited to receive either metformin (n = 40) or orlistat (n = 40). Weight, BMI, waist, serum LH, total serum testosterone and lipid profile were assessed at baseline and after 3 months. The subjects' ovulatory status was assessed after 3 months.. There was no significant difference in ovulation between the two treatment groups (30% vs 15%). Treatment with either drug showed a significant decline in body weight, BMI (Body Mass Index), and waist circumference, but the degree of decline in both groups was the same. Patients who were treated with orlistat, showed a significant reduction in total testosterone and serum lipid. Women in metformin group showed a significant reduction in serum LH.. Both metformin and orlistat showed a similar effect on weight loss and ovulation rates.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Female; Humans; Hypoglycemic Agents; Lactones; Lipids; Metformin; Obesity; Orlistat; Ovulation; Polycystic Ovary Syndrome; Testosterone

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

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

We investigated the factors influencing triglycerides (TG) reduction during ezetimibe, alone or combined with orlistat, administration. Eighty-six obese hypercholesterolemic subjects were prescribed a low-fat diet and were randomized to ezetimibe (E group), orlistat (O group), or both (OE group) for 6 months. Plasma TG and apolipoprotein (apo) C-III reduction was significantly greater in the combination group compared with monotherapy. Multivariate analysis showed that in E group apoC-III reduction and baseline TG levels were independently positively correlated, whereas baseline apoC-II levels were negatively correlated, with TG lowering. In OE group apoC-III reduction was the only independent contributor to TG reduction.

Topics: Anti-Obesity Agents; Anticholesteremic Agents; Apolipoprotein C-II; Apolipoprotein C-III; Azetidines; Diet, Fat-Restricted; Drug Therapy, Combination; Ezetimibe; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Triglycerides

To evaluate the effects of 1-year treatment with orlistat compared with placebo on different inflammatory parameters in type 2 obese diabetic patients.. Two hundred and fifty-four type 2 diabetic patients were randomized to take orlistat 120 mg three times a day or placebo for 12 months. We evaluated at baseline and after 3, 6, 9 and 12 months: leptin, tumor necrosis factor (TNF)-alpha, adiponectin (ADN), vaspin and high-sensitivity C-reactive protein (HS-CRP), body weight, waist circumference, body mass index (BMI), lipid profile, glycemic profile, fasting plasma insulin (FPI) and homeostasis model assessment insulin resistance index (HOMA-IR).. Regarding inflammatory parameters, there was a significant improvement of ADN and TNF-alpha, and a faster decrease of leptin and HS-CRP in the orlistat group compared with the control group. We also recorded a significant reduction of body weight and BMI with orlistat, but not with placebo. A faster improvement of glycemic profile and FPI was obtained with orlistat compared with the controls. Also, there was a significant reduction of lipid profile with orlistat, not reached with placebo.. Orlistat was more effective than placebo in ameliorating inflammatory parameters such as ADN and TNF-alpha, and anthropometric parameters.

Topics: Adiponectin; Anti-Obesity Agents; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Italy; Lactones; Leptin; Lipids; Male; Middle Aged; Obesity; Orlistat; Placebo Effect; Serpins; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Waist Circumference

Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.

Topics: Anti-Obesity Agents; Body Weight; Carnitine; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Inflammation; Insulin Resistance; Lactones; Male; Middle Aged; Obesity; Orlistat

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, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP (r=0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 (r=-0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Eating; Enteric Nervous System; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Insulin; Lactones; Male; Obesity; Orlistat; Peptide YY; Radionuclide Imaging; Stomach; 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

To assess the efficacy, pharmacodynamics, safety and tolerability of a range of doses of cetilistat, a novel inhibitor of gastrointestinal lipases, in healthy volunteers.. Three Phase I, randomized, placebo-controlled, parallel-group studies were conducted. Enrolled subjects in the three studies (n = 99) received a controlled calorie diet (total intake 2160 calories daily, 30% from fat). Twenty-four subjects were randomized to placebo and 66 were randomized to the following cetilistat doses: 50 mg three times daily [t.i.d. (n = 7)], 60 mg t.i.d. (n = 9), 100 mg t.i.d. (n = 7), 120 mg t.i.d. (n = 9), 150 mg t.i.d. (n = 16), 240 mg t.i.d. (n = 9) and 300 mg t.i.d. (n = 9). Nine subjects received the approved orlistat dose (120 mg t.i.d.). Treatment was for 5 days, with a 2-day run-in period and 1-day post-treatment follow-up. The primary outcome measure was daily faecal fat excretion. Secondary outcomes included plasma lipid levels, tolerability [gastrointestinal adverse events (AEs)] and safety.. Cetilistat increased faecal fat excretion relative to baseline at all doses. Cetilistat was well tolerated, with gastrointestinal AEs the most common (51%). Steatorrhoea (oily stool) was more frequent in the orlistat group (4.11 events per subject) than in any cetilistat dose group (0.14-1.81 events per subject). Most AEs (98%) were mild or moderate in intensity.. Cetilistat increased dietary fat excretion in healthy volunteers receiving a controlled calorie diet. Cetilistat was well tolerated at all doses examined and tolerability appeared to be improved relative to orlistat. Faecal fat excretion in the cetilistat groups was at least comparable to the orlistat 120 mg t.i.d. group.

Topics: Adolescent; Adult; Anti-Obesity Agents; Benzoxazines; Dietary Fats; Double-Blind Method; Enzyme Inhibitors; Humans; Intestinal Absorption; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; 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 objective was to investigate in a group of obese subjects the course in skeletal muscle phospholipid (SMPL) fatty acids (FA) during a 24-weeks weight maintenance program, which was preceded by a successful very low calorie dietary intervention (VLCD). Special focus was addressed to SMPL omega-3 FA, which is a lipid entity that influences insulin action.. Nine obese subjects (BMI = 35.7 +/- 1.0 kg/m(2)), who had completed an 8 weeks VLCD (weight-loss = -9.7 +/- 1.6 kg, P < 0.001), had obtained skeletal muscle biopsies (vastus lateralis) before and after a dietician-guided 24-weeks weight-maintenance program (-1.2 +/- 1.5 kg, P = ns). SMPL FA composition was determined by gas liquid chromatography. During the preceding VLCD, insulin sensitivity (HOMA-IR) and glycemic control (HbA1c) improved but no change in SMPL omega-3 FA was observed. During the weight-maintenance program five subjects received the pancreas lipase inhibitor Orlistat 120 mg t.i.d. versus placebo.. HOMA-IR and HbA1c stabilized and SMPL total omega-3 FA, docosahexaenoic acid and ratio of n-3/n-6 polyunsaturated FA increased by 24% (P < 0.01), 35% (P < 0.02) and 26% (P < 0.01), respectively, whereas saturated and monounsaturated FA did not change. Plasma total-cholesterol and LDL-cholesterol, which decreased during the VLCD, reverted to pre-VLCD levels (P < 0.01). Orlistat therapy was associated with weight-loss (P < 0.05), trends for better glycemic control (P = 0.15) and greater increase in SMPL docosahexaenoic acid (P = 0.12) but similar reversal of plasma cholesterols compared to placebo.. The data are consistent with the notion that greater SMPL omega-3 FA obtained during a weight-maintenance program may play a role for preserving insulin sensitivity and glycemic control being generated during a preceding VLCD.

Topics: Body Mass Index; Caloric Restriction; Diet, Reducing; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Enzyme Inhibitors; Fatty Acids; Female; Follow-Up Studies; Humans; Insulin Resistance; Lactones; Lipase; Lipids; Middle Aged; Muscle, Skeletal; Obesity; Orlistat; Phospholipids; Pilot Projects; Triglycerides

To compare the effects of ezetimibe plus orlistat or rimonabant on anthropometric and lipid parameters in nondiabetic statin-intolerant overweight/obese patients with dyslipidemia.. Thirty participants received a hypocaloric diet and were randomized to open-label combination of ezetimibe (10 mg/day) with orlistat (120 mg, 3 times a day with meals; ezetimibe/orlistat [EO], n = 15) or rimonabant (20 mg/day; ezetimibe/rimonabant [ER], n = 15). Anthropometric and metabolic variables were assessed at baseline and 3 months posttreatment. Similar reductions in body weight, body mass index, and waist circumference were recorded in both groups (-8.3%, -8.6%, and -5.2% in the EO group and -7.3%, -7.2%, and -7.0% in the ER group, P < .01 vs baseline for all). Low-density lipoprotein cholesterol (LDL-C) levels decreased in both treatment groups, but this reduction tended to be more pronounced in the EO group (28.4% vs 15.3%, respectively; P < .01 vs baseline for both). Triglycerides tended to decrease more in the ER compared with the EO group (-20.4% vs -14.1%, P < .01 vs baseline for both). High-density lipoprotein cholesterol (HDL-C) levels tended to decrease in EO group, but remained unaltered with ER treatment. Apolipoprotein B levels were equally reduced in both treatment groups.. For similar body weight reduction, the combination of ezetimibe with orlistat may be more efficient in LDL-C lowering, whereas the combination of ezetimibe with rimonabant may be more potent in terms of improving HDL-C and triglycerides.

Topics: Anti-Obesity Agents; Anticholesteremic Agents; Azetidines; Body Weight; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Male; Middle Aged; Obesity; Orlistat; Overweight; Piperidines; Pyrazoles; Rimonabant

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

To compare the clinical efficacy and safety of domestic orlistat and imported orlistat in Chinese overweight and obese patients.. In a randomized, double-blinded and positive-controlled study, 228 adults (BMI 24- < 40 kg/m(2)) evaluated at seven research centers were randomized to receive domestic orlistat or imported orlistat 120 mg 3 times a day with an energy-controlled diet for 24 weeks.. After 24 weeks, domestic orlistat treated patients got significant weight-loss (5.0 +/- 3.7) kg, which was comparable with that of imported orlistat treated patients (4.5 +/- 3.5) kg (P = 0.3922). Compared with the findings before treatment, there was significant decrease of systolic blood pressure (4.4 +/- 11.5) mm Hg (1 mm Hg = 0.133 kPa) and serum levels of TC (0.54 +/- 0.79) mmol/L and LDL-C (0.32 +/- 0.64) mmol/L in the domestic orlistat treated group (compared with levels of baseline, P < 0.0001). There was no significant difference between the two groups in the changes of blood pressure and lipid levels. Both groups had similar adverse event profiles, most of which were mild and transient gastrointestinal events. There were no serious adverse events in both groups.. Domestic orlistat combined with a light low-energy diet promoted significant weight loss, which was comparable with that of imported orlistat after 24 weeks of treatment. There was also improvement in blood pressure and serum levels of TC and LDL-C. Domestic orlistat was as effective and safe as imported orlistat in the treatment of obesity.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Asian People; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Overweight; Treatment Outcome; Young Adult

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

Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease.. To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months.. In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease.. The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients.. Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Cholesterol; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lactones; Male; Middle Aged; Obesity; Orlistat; Severity of Illness Index; Triglycerides; Young Adult

Increased concentrations of low density lipoprotein cholesterol (LDL-C), as well as of small dense LDL-C (sdLDL-C), are considered as cardiovascular risk factors.. An assessment of the effects of ezetimibe and orlistat administration, alone or in combination, on LDL-C and sdLDL-C levels (primary endpoint), as well as on anthropometric variables and metabolic parameters (secondary endpoints) in overweight and obese patients [body mass index (BMI)>28 kg/m(2)] with hypercholesterolaemia [total cholesterol>200 mg/dL (5.2 mmol/L)].. Eighty six subjects were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, 3 times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months.. Significant reductions in LDL-C (-19%, -21%, -32% in groups O, E and OE, respectively, all p<0.01 vs. baseline) and sdLDL-C levels (-45%, -48%, -76% in groups O, E, OE, respectively, all p<0.01 vs. baseline) were observed. Group OE experienced a significantly greater reduction in LDL-C and sdLDL-C levels compared with groups O and E (p<0.05). Furthermore, significant reductions of BMI, homeostasis model assessment (HOMA) index, serum uric acid, transaminase activities and plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity were observed in the O and OE groups. Gamma-glutamyl transpeptidase activity and Lp-PLA(2) activity improved significantly more with the combination treatment compared with either orlistat or ezetimibe monotherapy.. Orlistat and ezetimibe combination had a more favourable effect on LDL-C and sdLDL-C levels in overweight and obese hypercholesterolaemic patients than either drug alone. Furthermore, orlistat, alone or in combination with ezetimibe, additionally improved several anthropometric and metabolic variables.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Anti-Obesity Agents; Anticholesteremic Agents; Azetidines; Body Mass Index; Caloric Restriction; Cholesterol, LDL; Diet, Fat-Restricted; Drug Therapy, Combination; Ezetimibe; Female; gamma-Glutamyltransferase; Homeostasis; Humans; Hypercholesterolemia; Lactones; Male; Middle Aged; Obesity; Orlistat; Overweight; Treatment Outcome; Uric Acid

Orlistat is a reversible lipase inhibitor for obesity management. Orlistat exerts its pharmacological activity in the lumen of the stomach and small intestine by binding with the active site of gastric and pancreatic lipases, with the consequent inhibition of the systemic absorption of dietary fat. The undigested triglycerides are not absorbed, resulting in caloric deficit and positive effect in weight control. The objective of this study was to assess, using fat excreted in feces, the pharmacodynamic equivalence of orlistat when administered as generic and innovator capsule formulations.. A total of 18 healthy volunteers (12 males and 6 females) followed a 5-day run-in diet period in order to become accustomed to a high fat diet. Subjects were then randomized to receive under fed conditions oral doses of orlistat (120 mg) 3 times daily for 10 consecutive days as the generic (Ranbaxy Laboratories) or innovator (Xenical, Roche Laboratories, Nutley, NJ, USA) capsule formulations. Subjects followed a standardized diet (2,500 kcal/day, 30% as fat) for the entire study. Feces were collected over the last 2 days of the run-in period (baseline) and over the last 5 days of the 2 treatment periods. The amount of fat in meals and feces was assayed with a limit of detection of 0.1 and 0.2%, respectively. Fecal fat excretion over 24 hours (FFE(24), calculated as the percentage of amount of fat excreted in feces relative to the amount of fat ingested) was used as a pharmacodynamic endpoint to assess the therapeutic equivalence between the 2 orlistat formulations. An analysis of variance (ANOVA) was performed on FFE(24) parameters.. Mean FFE(24) values at baseline and after repeated oral administrations of the generic and innovator formulations of orlistat were 6.48, 20.0 and 19.6%, respectively. The ratio of least-squares means (LSM) of FFE(24) of the generic to the innovator formulation was 99.1%, with 90% confidence intervals of 83.8 -114.5%. Adverse events for the generic and innovator products were similar in nature and frequency.. Mean FFE(24) values were used as pharmacodynamic endpoints to assess equivalence between 2 formulations of orlistat. Results from this study suggest that pharmacodynamics of the generic capsule formulation of orlistat were similar to the marketed capsule formulation based on FFE(24) values.

Topics: Adult; Analysis of Variance; Anti-Obesity Agents; Capsules; Cross-Over Studies; Dietary Fats; Drug Administration Schedule; Drugs, Generic; Fats; Feces; Female; Humans; Lactones; Male; Obesity; Orlistat; Therapeutic Equivalency

We assessed the impact of a prolonged lipase inhibition upon gastric emptying (GE) and orocecal transit time (OCTT) of a 355-kcal low-fat solid meal.. In double-blind manner, 40 obese women BMI > 30 kg/m2, randomly allocated into two equal groups, took orally t.i.d. 120 mg orlistat or placebo during 8 weeks of a weight-reducing management. At randomization and after 2 months, GE was measured simultaneously with OCTT by means of a 13C-octanoic acid and a hydrogen breath test, respectively. Lipolytic activity was evaluated with a 13C-mixed triglyceride breath test (13C-MTGBT).. A profound lipase inhibition by orlistat was confirmed by a 79.5% +/- 16.9% reduction of the cumulative 6-h 13C recovery with 13CMTGBT. GE remained unchanged either in the orlistat (T1/2, 188 +/- 35 min start versus 198 +/- 36 min end) or the placebo (T1/2, 191 +/- 35 min start versus 180 +/- 39 min end) group. OCTT increased from 208 +/- 54 min to 271 +/- 64 min (P < 0.01) after orlistat treatment and did not change significantly (216 +/- 76 vs. 234 +/- 72 min) in the placebo group.. No adverse effect on the GE and a moderate prolongation of the OCTT of a low-fat solid meal is to be expected under a prolonged treatment with orlistat at a typical dosage regimen.

Topics: Administration, Oral; Adult; Anti-Obesity Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Food; Gastric Emptying; Gastrointestinal Transit; Humans; Jejunum; Lactones; Lipase; Obesity; Orlistat; Prospective Studies; Time Factors; Treatment Outcome

Leptin is likely to be involved in the homeostasis of body weight. This study aimed to examine the acute effects of orlistat on postprandial serum glucose, insulin, and leptin levels before any effect on body weight occurred.. Thirty-four nondiabetic, obese patients were enrolled in this study (body mass index, 35.7+/-3.8 kg/m(2)). Patients were randomly assigned to two groups, one receiving orlistat (120 mg, single dose), and the other received a placebo. A single dose was given before a standard 600-kcal mixed meal containing 60% carbohydrates, 25% lipids, and 15% protein. Blood samples were collected basally before the test meal and then hourly for five hours. Graphic tendencies, peak values, time needed to reach the peak values, and area under the curve values were compared between groups.. There were no differences in sex distribution, mean age, anthropometric measurements, and basal glucose, insulin, and leptin levels between the orlistat and placebo groups. Hourly serum glucose and insulin changes were similar between groups, peak levels of insulin occurred in the first hour in control group, although peak levels of insulin did not occur until the second hour in patients in the orlistat group. Also, serum leptin levels had a more horizontal and delayed increase after a mixed meal in patients in the orlistat group than they did in patients in the placebo group. There were no statistically significant differences between the groups.. One dose of 120 mg orlistat made no changes in postprandial serum glucose, insulin, and leptin levels, although leptin-level increases were smaller in patients receiving orlistat.

Topics: Aged; Blood Glucose; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Homeostasis; Humans; Hypolipidemic Agents; Insulin; Lactones; Leptin; Lipids; Middle Aged; Obesity; Orlistat; Postprandial Period

High-density lipoprotein (HDL) includes discrete subfractions. HDL exhibits anti-atherogenic properties, which have been partly linked to the activity of HDL-associated enzymes, such as the lipoprotein associated phospholipase A(2) (HDL-LpPLA(2)) and paraoxonase-1 (PON1).. We assessed in an open-label randomised study the effect of orlistat and ezetimibe, alone or in combination, on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects (body mass index > 28 kg/m(2)) with hypercholesterolemia [total cholesterol > 200 mg/100 ml (5.2 mmol/l)].. Eighty-six people were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, three times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months. HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method.. Levels of HDL cholesterol (HDL-C) and apolipoprotein AI did not change significantly in any group. In group O the cholesterol concentration of HDL-2 subclass increased significantly, while the cholesterol of HDL-3 subclass decreased significantly. In groups E and OE HDL-2 subclass did not significantly change, while the cholesterol concentration of HDL-3 subclass decreased significantly. We observed a non-significant decrease in the HDL-LpPLA(2) and PON1 activity in all groups. However, the ratios of both enzyme activities to low-density lipoprotein cholesterol (LDL-C) levels (an index of atherogenicity) significantly increased in all groups.. Although HDL-C levels did not change after treatment with orlistat and ezetimibe, alone or in combination, there were alterations of the HDL-2 and HDL-3 subclasses. The activity of HDL-LpPLA(2) and PON1 per mg LDL-C increased significantly in all groups.

Topics: Adult; Anti-Obesity Agents; Anticholesteremic Agents; Aryldialkylphosphatase; Azetidines; Body Mass Index; Cholesterol, HDL; Diet, Fat-Restricted; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hyperlipidemias; Lactones; Linear Models; Lipoproteins, HDL2; Lipoproteins, HDL3; Male; Middle Aged; Obesity; Orlistat; Phospholipases A2; Time Factors; Treatment Outcome

We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS).. Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay.. We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy.. OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.

Topics: Anti-Obesity Agents; Body Mass Index; Cholesterol, HDL; Drug Therapy, Combination; Female; Fenofibrate; Greece; High-Density Lipoproteins, Pre-beta; Humans; Hypolipidemic Agents; Lactones; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Overweight

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

Undesirable metabolic effects of modern antipsychotics, especially clozapine and olanzapine, merit development of new weight-control strategies, including pharmacologic ones. We investigated the feasibility of treatment with orlistat, a weight-control drug with no central effects, for overweight/obesity in clozapine- or olanzapine-treated male and female patients.. Add-on orlistat was prescribed for 16 weeks in a randomized, double-blind, placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years, with no compliance with nonpharmacologic programs or hypocaloric diet required. The primary efficacy variable was body weight change. The study was conducted from 2004 through 2005.. Of 71 randomly assigned subjects, 63 were eligible for modified intent-to-treat analysis. While no statistically significant effect was observed in the whole population, male (but not female) patients benefited from treatment with orlistat (-2.36 kg vs. 0.62 kg on placebo, p = .011). There were 5 responders (16.1%) (those with >or= 5% weight loss) that received orlistat versus 2 responders (6.3%) that received placebo (number needed to treat = 11), but the difference was not statistically significant.. Without a hypocaloric diet, the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men. More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Obesity; Olanzapine; Orlistat; Overweight; Psychotic Disorders

The purpose of this study was to examine the possible effects of a gastrointestinal lipase inhibitor "Orlistat (Xenical)" on the intestinal absorption of oxalate and thereby on the urinary levels of oxalate excretion in overweight patients.. Long-term follow-up data of 95 cases (57 men, 38 women; M/W=1.5) were documented. Patients were randomly assigned into two groups. While the patients in group I (n=55) were treated with orlistat (Xenical) for 6 months, patients in group II (n=40) received no specific medication. Calcium, oxalate, and citrate levels were determined in a 24-h urine collection from each patient. To evaluate the significance in the groups as well as the differences between the two groups, ANOVA test was performed and the results were given as mean +/- s.d.. Comparative evaluation of urinary oxalate levels during 3-month follow-up clearly showed that urinary oxalate excretion significantly increased in 34/55 patients (61.8%) in the first group (P<0.05). Of these 34 patients, 30 (88.2%) continued to have increased urinary oxalate excretion during 6-month follow-up (P=0.001). However, our data did not show any significant effect of this medication on urinary citrate and calcium levels during 3- and 6-month follow-up evaluation (P=0.05).. Our results suggest that increased intestinal absorption of dietary oxalate due to this type of medication in obese patients could make a substantial contribution to urinary oxalate excretion and may increase the risk of stone formation.

Topics: Adult; Anti-Obesity Agents; Calcium; Citric Acid; Enzyme Inhibitors; Female; Humans; Hyperoxaluria; Intestinal Absorption; Intestines; Lactones; Lipase; Male; Obesity; Orlistat; Oxalic Acid; Risk Assessment; Treatment Outcome; Up-Regulation; Urinary Calculi

Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS).. The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients (body mass index>28 kg/m(2)) with MetS.. Patients (n=89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200mg/day (F group) or both (OF group) for 6 months.. Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p<0.05) together with a greater increase in LDL particle diameter (p<0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly decreased in all treatment groups. The reduction of Lp-PLA(2) was more pronounced with OF administration compared with each monotherapy (p<0.05).. Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Anti-Obesity Agents; Cardiovascular Diseases; Cholesterol, LDL; Drug Therapy, Combination; Female; Fenofibrate; Humans; Hypolipidemic Agents; Lactones; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Overweight; Phospholipases A2; Risk Factors

Previous studies have demonstrated that oxidative stress is increased in obese patients. The high-density lipoprotein (HDL) associated human paraoxonase 1 (PON1) can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Our objective was to assess the effects of orlistat therapy combined with diet on body mass index (BMI), waist circumference, lipid parameters, blood pressure, serum glucose level and PON1 activity.. A longitudinal, multicenter, randomized study with and without orlistat treatment was performed. One hundred thirty nine otherwise healthy, obese subjects were divided in to two groups: 78 persons received orlistat (120 mg three times a day) combined with diet while 61 persons were kept on diet only. Anthropometrical parameters, serum lipid levels and PON1 activity were measured at baseline and after 6 months of treatment. BMI and waist circumference were reduced more pronouncedly in the orlistat group than in the control group. Patients receiving orlistat also had significantly greater improvements in fasting blood glucose levels and blood pressure. The orlistat-treated group showed a greater reduction in total cholesterol and triglyceride levels. In addition, the serum PON1 activity in these patients was significantly increased compared to the diet-only group.. The 6-month treatment with orlistat had a beneficial effect on the lipid profile and improved the antioxidant status by increasing serum PON1 activity. However, because of the limited therapeutic effectiveness, obese patients with hypercholesterolemia should receive additional lipid lowering medications.

Topics: Adult; Aged; Anti-Obesity Agents; Aryldialkylphosphatase; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Lactones; Lipid Peroxidation; Longitudinal Studies; Male; Malondialdehyde; Middle Aged; Obesity; Orlistat

To investigate the efficacy of orlistat on the maintenance of weight loss over 3 years following a major weight loss induced by very-low-energy diet (VLED) in obese patients with metabolic risk factors such as dyslipidemia, impaired fasting glucose, and diet-treated type 2 diabetes.. Initially, weight loss was induced by an 8-week VLED (600-800 kcal/day) in 383 patients with a mean BMI of 37.5 kg/m(2) (range 30.0-45.2). Those who lost > or = 5% of their body weight (309 of 383 patients) were then randomized to receive lifestyle counseling for 3 years together with either orlistat 120 mg t.i.d. or matching placebo capsules. Primary end points were the maintenance of > or = 5% weight loss after 3 years. Additionally, differences in the development of type 2 diabetes between orlistat and placebo were analyzed.. The VLED induced a mean weight loss of 14.4 +/- 2.0 kg among the subsequently randomized patients. The mean weight gain after 3 years was lower with orlistat than with placebo (4.6 +/- 8.6 vs. 7.0 +/- 7.1 kg; P < 0.02). The number of participants who achieved > or =5% weight loss also favored orlistat (67 vs. 56%; P = 0.037). Waist circumference was significantly more reduced in the orlistat group (P < 0.05), but no other differences in the risk factors were observed between the two groups. The incidences of new cases of type 2 diabetes were significantly reduced in the orlistat group (8 cases out of 153 subjects) versus placebo (17 cases out of 156 subjects) (P = 0.041).. The addition of orlistat to lifestyle intervention was associated with maintenance of an extra 2.4 kg weight loss after VLED for up to 3 years in obese subjects. The combination of orlistat and lifestyle intervention was associated with a reduced occurrence of type 2 diabetes.

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Body Size; Combined Modality Therapy; Diabetes Complications; Diet, Reducing; Female; Glucose Intolerance; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Placebos; Weight Gain

BACKGROUND Women with polycystic ovary syndrome (PCOS) exhibit elevated serum advanced glycation end-products (AGE) compared with healthy subjects. Short-term administration of orlistat has been shown to reduce the postmeal increase in serum AGE levels in women with PCOS and in controls.. To evaluate the long-term effect of orlistat and a low-calorie diet on serum AGE levels, and on the hormonal and metabolic profile of obese PCOS and normal women.. A clinical trial of 6 months of orlistat administration with an energy-restricted diet [basic metabolic rate (BMR) 600 kcal/day] in all subjects.. Twenty-nine women with PCOS [aged 27.52 +/- 5.77 years; body mass index (BMI) 35.43 +/- 5.31 kg/m(2)] and 18 controls (aged 32.06 +/- 5.64 years; BMI 36.39 +/- 6.47 kg/m(2)).. Serum AGE levels (U/ml), hormonal and metabolic profile.. PCOS and controls did not differ in BMI (P = 0.58), waist-to-hip ratio (WHR) (P = 0.44), fasting insulin concentration (P = 0.45) and glucose-to-insulin ratio (GIR) (P = 0.34). PCOS women exhibited statistically higher AGE (P < 0.001) and testosterone levels (P < 0.001) compared with controls. After 6 months of orlistat treatment, AGE levels showed a statistically significant decrease in both groups (PCOS: baseline 9.08 +/- 1.84, post-orlistat 8.56 +/- 1.95, P = 0.001; controls: baseline 5.02 +/- 0.62, post-orlistat 4.91 +/- 0.69, P = 0.03), independently of the BMI reduction in the PCOS group. A significant reduction was observed in BMI (PCOS: P < 0.001; controls: P < 0.001), WHR (PCOS: P = 0.002; controls: P = 0.04), fasting insulin (PCOS: P < 0.001; controls: P = 0.008), and testosterone concentrations in PCOS (P < 0.001). SHBG concentration (PCOS: P = 0.004; controls: P = 0.008) and GIR (PCOS: P < 0.001; controls: P = 0.03) were significantly increased. A significant improvement was also observed in insulin resistance indices post-treatment in both groups.. Our data suggest that orlistat has a beneficial effect in reducing elevated AGE levels and improving the hormonal and metabolic profile in women with PCOS after 6 months of treatment, independently of BMI changes.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Case-Control Studies; Diet; Drug Administration Schedule; Female; Glycation End Products, Advanced; Humans; Insulin; Lactones; Linear Models; Lipase; Obesity; Orlistat; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Waist-Hip Ratio

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

Glucagon-like peptide-1 is an insulin secretion-stimulating gut hormone that is produced in response to food intake. Orlistat (Xenical, F. Hoffman-La Roche, Basel, Switzerland), which decreases fat absorption and increases intestinal fat content, may therefore affect the secretion of glucagon-like peptide-1. In this study we examined the immediate effects of orlistat on postprandial serum glucose, insulin and glucagon-like peptide-1 levels prior to a change in body weight.. Randomized, clinical study.. Sixteen nondiabetic obese patients (body mass index 35.7 +/- 3.8 kg/m(2), range 32.5-43.1) were enrolled in this study. The patients were randomly assigned to either the group treated with orlistat (120 mg, single dose) or the control group. There were eight patients in each of the two groups. Orlistat was given before a standard 600-kcal mixed meal containing 60% carbohydrates, 25% lipids and 15% protein. Blood samples were collected at baseline and at 30-min intervals for 180 min after the test meal. Graphical tendencies, peak value, time to reach the peak value, and area under the curve in the two groups were compared.. Blood samples were obtained for the measurement of GLP-1, glucose, insulin, high density lipoprotein, total cholesterol and triglycerides.. We found no difference in sex distribution, mean age, anthropometric measurements, or baseline glucose, insulin and glucagon-like peptide-1 levels between the orlistat and placebo groups. The peak insulin and glucagon-like peptide-1 levels were determined at 60 min in the control group. Hourly changes in serum glucose and insulin levels were similar between the groups, although the peak insulin and glucagon-like peptide-1 levels were reached at 120 min in the orlistat group. There were no statistically significant differences between the groups.. A single dose of 120-mg orlistat caused no change in postprandial serum glucose, insulin or glucagon-like peptide-1 levels in nondiabetic obese patients. Although glucagon-like peptide-1 increases were delayed in the orlistat group, these changes were nonsignificant.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Insulin; Lactones; Male; Middle Aged; Obesity; Orlistat

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

Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity. Because of orlistat's mode of action, increased fecal fat is presented to the colonic mucosa, and fecal bile acid and free fatty acid composition may be altered during treatment. Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation.. Twenty-four obese (body mass index, 30-40 kg/m2) but otherwise healthy male and female subjects were enrolled in a single-center, randomized, double-blind, placebo-controlled, parallel-group study. Participants were hospitalized during days 1-3 and 33-42 of treatment and were treated as outpatients for the remaining days.. Treatment with orlistat for 6 weeks resulted in significantly greater increases in fecal weight, total fecal fat, and fecal free fatty acids than placebo. Total fecal bile acid amounts decreased slightly with orlistat, and increased significantly with placebo treatment (P < .05 between-group difference). Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices (5-bromo-2-deoxyuridine, whole crypt mitotic count, and proliferating cell nuclear antigen).. Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation, a putative biomarker of colon cancer risk.

Topics: Adult; Aged; Anti-Obesity Agents; Bile Acids and Salts; Biopsy; Bromodeoxyuridine; Cell Proliferation; Colon; Diet, Fat-Restricted; Dietary Fats; Double-Blind Method; Fatty Acids; Feces; Female; Humans; Lactones; Male; Middle Aged; Mitotic Index; Obesity; Orlistat; Proliferating Cell Nuclear Antigen

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

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

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

The aim of the study was to assess the adjunctive effects of orlistat on weight loss and the influence of weight reduction on glycaemic control in overweight Chinese female type 2 diabetic patients. A randomised, placebo-controlled, double-blind, 12-week study was conducted. Chinese female type 2 diabetic patients, overweight (body mass index > 25 kg/m(2)), poorly controlled glucose levels [glycosylated haemoglobin (HbA1c) > 8%], were randomly assigned to two groups. In addition to their oral hypoglycaemic agents (maximal doses of sulphonylureas and metformin), one group (n = 30) received a placebo and the other (n = 30) received orlistat 120 mg t.i.d. for 12 weeks. Comparing the changes that occurred after 12 weeks in the orlistat and placebo groups, the former showed significantly greater reduction in bodyweight (2.5 vs. 0.4 kg; p < 0.05), fasting plasma insulin level (p < 0.01), 2-h postprandial blood glucose after glucose challenge (p < 0.01), insulin resistance (p < 0.01), HbA1c (p < 0.05), total cholesterol and triglyceride levels (p < 0.05, respectively). No significant differences were found between treatment groups in blood pressure and heart rate. The addition of orlistat to oral hypoglycaemic agents resulted in a significant weight reduction and improvement of metabolic control in overweight Chinese female type 2 diabetic patients.

Topics: Anti-Obesity Agents; Body Mass Index; Caloric Restriction; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Lactones; Obesity; Orlistat; Prospective Studies; Treatment Outcome

Obesity and its associated metabolic complications can impair the physiologic regulation of fibrinolysis, leading to a hyper coagulable state. We aimed to assess circulating thrombin activatable fibrinolysis inhibitor (TAFI) levels in obese female patients and to test the effects of orlistat-induced weight loss on basal TAFI concentrations. Obese female outpatients age 18 and older, with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) of at least 30, were included into the study. Thirteen nonobese (median BMI, 22.60 kg/m(2)) age-matched females were taken as controls. Plasma TAFI levels were measured before orlistat administration and after 6 months of orlistat treatment in the obese group and only one measurement was done in the control group. Twenty-seven obese patients were recruited into the study. The median TAFI level of the control group was 124.00; this value was significantly lower than the basal TAFI level of the obese group (p < 0.001). TAFI levels after orlistat therapy were statistically significantly lower than basal TAFI levels (p < 0.001) in the obese group. Hemostatic abnormalities including TAFI alterations represent a link between obesity and vascular thrombosis. Effective interventions should be considered in improving the obesity-associated prothrombotic risk profile.

Topics: Adult; Body Weights and Measures; Carboxypeptidase B2; Case-Control Studies; Female; Hemostasis; Humans; Lactones; Middle Aged; Obesity; Orlistat; Thrombosis

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

Obesity poses a serious threat for health, being a risk factor for development of heart diseases, diabetes type II, tumors, and reproductive function failure. The aim of this study is to investigate the effect of orlistat (xenical) on the character of menstrual cycle and some metabolic indicators in women with obesity. 17 patients of reproductive age with I-III degree of obesity were investigated. The visceral type of obesity and disorders of menstrual cycle were observed in all patients: oligomenorrhea was observed in 9 (52.9%), amenorrhea in 4 (23.5%)and metrorrhagia in 4 (23.5 %) patients. All the patients received orlistat (xenical) 120 mg 3 times per day during 6 months. Orlistat (xenical) therapy results in significant reduction of body weight (12.3%), body mass index (13.3%), improvement of lipid and carbohydrates metabolisms. Normalization of hormonal levels was registered. As a result of all this the restoration of menstrual cycle and ovulation is registered. Orlistat (xenical) is effective in the treatment of women with obesity and menstrual cycle disorders.

Topics: Adult; Amenorrhea; Anti-Obesity Agents; Cholesterol, VLDL; Female; Humans; Lactones; Metrorrhagia; Obesity; Orlistat; Triglycerides

To specify changes in clinicolaboratory parameters in reduction of obesity in patients with diabetes mellitus type 2 (DM-2).. Antropometry, densitometry of fat tissue (FT) were made and parameters of fat and carbohydrate metabolism (lipidogram, glycated hemoglobin, immunoreactive insulin), FT secretory activity (leptin, adiponectin, TNF-alpha) were studied in 75 obese DM-2 patients. After the above primary examination all the patients were randomized into 2 groups: group 1 (n = 55) received xenical (120 mg 3 times a day) and kept moderate hypocaloric diet; group 2 (n = 20) received only the above diet therapy. Active treatment lasted 24 weeks.. In addition to symptoms of metabolic syndrome (MS) the patients were found to have secretory disturbances of FT activity: elevation of leptin and TNF-alpha levels, subnormal adiponectin. These alterations directly correlated with body mass, FT mass gain, increase in waist circumference. Hyperleptinemia, hyperinsulinemia and hypoadiponectinemia were considered as markers of insulin resistance (IR) and related conditions. Xenical promoted a significant weight loss resulting in a positive trend in the parameters of adipokines, fat and carbohydrate metabolism, in reduction of IR.. Xenical is beneficial for patients with DM-2 and obesity because it improves metabolic processes.

Topics: Adiponectin; Adipose Tissue; Anthropometry; Anti-Obesity Agents; Biomarkers; Body Weight; Caloric Restriction; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lactones; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Tumor Necrosis Factor-alpha

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

Obesity is a well-known risk factor of atherosclerosis. Recent studies showed that obesity is associated with enhanced lipid peroxidation. The aim of this study is to investigate the effect of weight reduction with orlistat treatment on lipid peroxidation levels. We assessed lipid peroxidation by measuring the concentration of plasma malondialdehyde (MDA).. A randomized, controlled, open-label 6-month study.. In total, 36 obese (body mass index (BMI) >30 kg/m2) and 11 healthy age-matched control subjects were enrolled in the study.. Fasting glucose, triglyceride, total cholesterol, HDL cholesterol and LDL cholesterol and MDA levels were measured in both groups. Obese subjects received orlistat, 120 mg three times daily together with hypocaloric diet. After 6 months of treatment laboratory tests were repeated.. MDA levels were significantly higher in obese patients than the control group (P<0.0001). After 6 months of treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Plasma MDA levels were significantly reduced by weight loss from 2+/-0.77 to 0.89+/-0.41 nmol/ml (P<0.001). BMI correlated with MDA levels at baseline (r=0.6, P<0.0001). Changes in BMI was positively associated with plasma MDA level reduction (r=0.36, P<0.05).. These results indicate that obesity is associated with increases in endogenous lipid peroxides. Our data show that the indicator of lipid peroxidation-MDA-falls markedly in association with weight loss with orlistat. The demonstration of decreased free radical generation has important implications for oxidative mechanism underlying obesity-associated disorders.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Diet, Reducing; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Obesity; Orlistat

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

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

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

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

The aim of this study is to compare the effect of orlistat vs. placebo on the predicted 10-year cardiovascular disease (CVD) risk in obese people with one or more cardiovascular risk factors treated for 12 months, in conjunction with a fat-reduced, but otherwise ad libitum, diet.. A double-blind, randomized, placebo-controlled, parallel study was performed in conjunction with a fat-reduced diet and physical activity advice for 1 year. Participants (n = 339) from eight centres in Australia and New Zealand were randomized to either orlistat (120 mg) three times daily (n = 104 women, 66 men; mean +/- s.d. age = 52.0 +/- 7.5 years, body mass index (BMI) = 37.6 +/- 5.1 kg/m(2)) or placebo three times daily (n = 89 women, 80 men; age = 52.5 +/- 7.4 years, BMI = 38.0 +/- 4.9 kg/m(2)). The primary efficacy criterion was the 10-year risk of developing CVD calculated from the Framingham equation. Secondary efficacy criteria were body weight, waist circumference, blood pressure and serum concentrations of triglycerides, cholesterol (total, LDL and HDL), glucose, insulin and glycated haemoglobin and quality of life.. There was no difference in the change in 10-year CVD risk between orlistat and placebo groups over 1 year. The orlistat group, however, had significant favourable changes in many of the individual CVD risk factors (total cholesterol, LDL-cholesterol, glucose, glycated haemoglobin, insulin, body weight and waist circumference) and one of the domains of quality of life measured by means of the SF-36 questionnaire (vitality), compared to the placebo group. Significant reductions in medication use for hypertension and diabetes were observed in the orlistat group, compared to those in placebo, but there were no significant differences in medication use for blood lipids.. Orlistat may have reduced CVD risk, as judged by the favourable changes in individual risk factors and reductions in medication use, but the method used in order to measure absolute CVD risk in this study (Framingham CVD equation) was not sensitive enough to detect the changes in this relatively low-risk group (approximately 10% of risk of a CVD event over 10 years).

Topics: Adult; Aged; Anti-Obesity Agents; Antihypertensive Agents; Blood Glucose; Body Constitution; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Diet, Reducing; Double-Blind Method; Exercise Therapy; Female; Humans; Hypoglycemic Agents; Insulin; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Probability; Risk Factors; Single-Blind Method

Evidence suggests that metabolic phenomena during postprandial lipemia may be important in the pathogenesis of atherosclerosis. Both lipid concentrations and lipoprotein subclass patterns may be important cardiovascular risk modifiers. The pancreatic lipase inhibitor orlistat reduces fat absorption by 30% and is used for the treatment of overweight and obesity. We evaluated the effect of orlistat on postprandial lipemia and lipoprotein particle distribution after moderate-and high-fat meals in healthy volunteers. In this double-blind, randomized, cross-over study, 10 healthy young men received orlistat 120 mg plus a high-fat meal (HFO), orlistat plus a moderate-fat meal (MFO) or placebo plus a high-fat meal (HFP). Plasma triacylglycerol, glucose, insulin, and free fatty acids were measured at baseline (fasting) and postprandially for 8h. Lipoprotein subclass profile was assessed by nuclear magnetic resonance spectroscopy. The 8h postprandial mean triacylglycerol area under the curve (AUC) was significantly lower with MFO and HFO (0.79 versus 1.33 mmol/lh) versus HFP (4.33 mmol/lh; p=0.02). Mean change in large VLDL subclass concentration during the 4-8h and mean VLDL size after 8h was significantly lower with HFO and MFO versus HFP (p<0.001). Small HDL particle concentration decreased significantly with HFP versus MFO or HFO (p<0.001). There was no significant difference in postprandial concentrations of glucose, insulin or free fatty acids on the different regimens. The lowering of postprandial triacylglycerol AUC, shorter postprandial lipemia, lower concentration of large triacylglycerol-rich particles and decrease of VLDL particle size supports the hypothesis of a less atherogenic postprandial lipoprotein profile following orlistat ingestion.

Topics: Adult; Anti-Obesity Agents; Dietary Fats; Humans; Hyperlipidemias; Lactones; Lipase; Lipoproteins; Male; Nuclear Magnetic Resonance, Biomolecular; Obesity; Orlistat; Particle Size; Postprandial Period

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

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

Continence problems during treatment with orlistat (a lipase inhibitor) are caused when susceptible patients are exposed to increased volumes of loose, fatty stool.. To investigate the dose-response effects of loperamide on continence and anorectal function in subjects susceptible to continence problems on orlistat.. Ten obese subjects enterred a randomized controlled, double-blind study of loperamide at placebo, 2, 4, and 6 mg/day in a factorial design. Continence problems during orlistat treatment were self-assessed by patient diary. Anorectal function and continence were assessed by barostat, manometry, and retention testing.. Loperamide increased stool consistency with dose (p = 0.07) and this effect reduced continence problems during orlistat treatment (p < 0.05). A bell-shaped dose-response relationship was present with anal sphincter function (p < 0.01) and anorectal sensitivity (p < 0.01).. Loperamide has beneficial effects on stool consistency and continence in obese subjects taking orlistat. The effect on stool consistency appeared more important than effects on anorectal function.

Topics: Adult; Anal Canal; Anti-Obesity Agents; Antidiarrheals; Double-Blind Method; Fecal Incontinence; Female; Humans; Lactones; Loperamide; Male; Middle Aged; Obesity; Orlistat; Placebos; Rectum

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

Obesity is becoming increasingly common worldwide and is strongly associated with the metabolic syndrome (MetS). MetS is considered to be a cluster of risk factors that increase the risk of vascular events.. In an open-label randomised study (the FenOrli study) we assessed the effect of orlistat and fenofibrate treatment, alone or in combination on reversing the diagnosis of the MetS (primary end-point) as well as on anthropometric and metabolic parameters (secondary end-points) in overweight and obese patients with MetS but no diabetes.. Overweight and obese patients (N = 89, body mass index (BMI) > 28 kg/m2) with MetS [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria] participated in the study. Patients were prescribed a low-calorie low-fat diet and were randomly allocated to receive orlistat 120 mg three times a day (tid) (O group), micronised fenofibrate 200 mg/day (F group), or orlistat 120 mg tid plus micronised fenofibrate 200 mg/day (OF group). Body weight, BMI, waist circumference, blood pressure, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglyceride, creatinine (SCr) and uric acid (SUA) levels, as well as homeostasis model assessment (HOMA) index and liver enzyme activities were measured at baseline and after 3 months of treatment.. Of the 89 patients enrolled, three (one in each group) dropped out during the study due to side effects. After the 3-month treatment period, 43.5% of patients in the O group, 47.6% in the F group and 50% in the OF group no longer met the MetS diagnostic criteria (primary end-point, p < 0.0001 vs. baseline in all treatment groups). No significant difference in the primary end-point was observed between the three treatment groups. Significant reductions in body weight, BMI, waist circumference, blood pressure, TC, LDL-C, non-HDL-C, triglyceride and SUA levels, as well as gamma-glutamyl transpeptidase activity and HOMA index were observed in all treatment groups. In the OF group a greater decrease in TC (-26%) and LDL-C (-30%) was observed compared with that in the O and F groups (p < 0.01) and a more pronounced reduction of triglycerides (-37%) compared with that in the O group (p < 0.05). SUA levels and alkaline phosphatase activity decreased more in the F and OF groups compared with the O group (p < 0.05). Moreover, SCr significantly increased and estimated creatinine clearance decreased in the F and OF groups but they were not significantly altered in the O group (p < 0.01 for the comparison between O and either F or OF groups). Glucose (in groups O and OF), as well as insulin levels and HOMA index (in all groups), were significantly reduced after treatment (p < 0.05 vs. baseline).. The combination of orlistat and micronised fenofibrate appears to be safe and may further improve metabolic parameters in overweight and obese patients with MetS compared with each monotherapy.

Topics: Adult; Aged; Cholesterol, HDL; Cholesterol, LDL; Drug Therapy, Combination; Female; Fenofibrate; Humans; Lactones; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Overweight

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

It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients.. In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat.. Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).. Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].

Topics: Adult; Body Mass Index; Diabetes Mellitus; Double-Blind Method; Energy Intake; Female; Glucose Tolerance Test; Humans; Lactones; Life Style; Lipase; Male; Middle Aged; Obesity; Orlistat; Placebos; Prospective Studies

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

The intermittent loss of oil or liquid faeces ('spotting') is an adverse effect that occurs in obese patients during treatment with the lipase inhibitor orlistat; the pathophysiology is unknown.. To investigate the effects of orlistat on anorectal sensorimotor function and continence.. Obese subjects susceptible to spotting were identified by an unblind trial of orlistat. Obese spotters (n = 15) and non-spotters (n = 16) completed a randomized, double-blind, cross-over trial of orlistat and placebo. Anorectal function was assessed by rectal barostat and anal manometry, together with a novel stool substitute retention test, a quantitative measurement of faecal continence.. Orlistat increased stool volume and raised faecal fat and water. Treatment had no effect on anorectal motor function, but rectal sensation was reduced; on retention testing, the volume retained was increased. Subjects susceptible to spotting had lower rectal compliance, heightened rectal sensitivity and weaker resting sphincter pressure than non-spotters. On retention testing, gross continence was maintained; however, spotters lost small volumes of rectal contents during rectal filling.. Treatment with orlistat has no direct adverse effects on anorectal function or continence. Spotting occurs during treatment with orlistat when patients with sub-clinical anorectal dysfunction are exposed to increased stool volume and altered stool composition.

Topics: Adult; Anti-Obesity Agents; Cross-Over Studies; Double-Blind Method; Fecal Incontinence; Feces; Female; Humans; Lactones; Male; Manometry; Medical Records; Middle Aged; Obesity; Orlistat; Prospective Studies; Reproducibility of Results

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

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

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

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

This pilot study compared the efficacy of orlistat as an adjunctive treatment for obesity between African American and Caucasian adolescents. Twenty obese adolescents with obesity-related co-morbid conditions underwent measurements of body composition, glucose homeostasis by frequently sampled intravenous glucose tolerance test (FSIGT), and fasting lipids before and after 6 months treatment with orlistat 120 mg tid in conjunction with a comprehensive behavioral program. Weight (p < 0.05), BMI (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), fasting insulin (p < 0.02) and fasting glucose (p < 0.003) were lower after treatment. Insulin sensitivity, measured during the FSIGT, improved significantly (p < 0.02), as did fasting indices such as the homeostasis model assessment for insulin resistance (p < 0.01). African American subjects exhibited significantly less improvement in weight (p < 0.05), BMI (p < 0.01), waist circumference (p = 0.03), and insulin sensitivity (p = 0.05). Improvements in cholesterol were not significantly different between African Americans and Caucasians. We conclude that Caucasians lost more weight and had greater improvements in insulin sensitivity than African Americans, but both exhibited improvements in plasma lipids. The true benefit of orlistat treatment over a comprehensive behavioral program remains to be determined in placebo-controlled trials.

Topics: Administration, Oral; Adolescent; Behavior Therapy; Black or African American; Blood Glucose; Body Weight; Capsules; Cholesterol, LDL; Clinical Trials as Topic; Comorbidity; Drug Administration Schedule; Energy Metabolism; Female; Humans; Insulin Resistance; Lactones; Leptin; Male; Obesity; Orlistat; Pilot Projects; Treatment Outcome; White People

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

Orlistat and metformin are the currently used drugs for weight loss. We aimed to compare the effect of orlistat and orlistat plus metformin combination therapy on weight loss and insulin resistance in obese women.. In all, 57 obese women (body mass index >/=30 kg/m(2) and normal glucose tolerance) were included. All subjects took the same content and caloric diet therapy during the study. After a month of diet period, each individual was randomly assigned to receive 360 mg orlistat per day (group 1; n=30) or 360 mg orlistat plus 1700 mg metformin per day (group 2; n=27) during the next 3 months. Body weight and insulin resistance by the homeostasis model assessment model (HOMA-IR) was measured at baseline, first month and fourth month.. The mean weight loss in groups 1 and 2 was 1.36+/-0.8 kg (1.4+/-0.7%) and 1.11+/-0.7 kg (1.1+/-0.7%) from baseline to first month; 4.8+/-2.9 kg (5.28+/-3.0%) and 5.77+/-2.5 kg (6.17+/-2.9%) from first month to fourth month. Body weight was decreased in groups 1 (P< 0.001) and 2 (P< 0.001), but there was no statistically significant difference between groups. Change of HOMA-IR in groups 1 and 2 was 0.41+/-0.4 (14.9+/-10.1%) and 0.23+/-0.7 (8.16+/-12.3%) from baseline to first month; 0.49+/-0.77 (22.0+/-26%) and 0.95+/-0.88 (34.8+/-29.1%) from first month to fourth month. HOMA-IR value was decreased in groups 1 (P< 0.001) and 2 (P< 0.001) but was not different between groups during the study period.. Combination of orlistat with metformin did not result in an additional effect on weight loss and insulin resistance when compared to orlistat alone in our study. However, new studies which have more sample sizes and the longer study period are necessary for this purpose.

Topics: Adult; Dietary Fats; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Intestinal Absorption; Lactones; Lipase; Metformin; Middle Aged; Obesity; Orlistat; Prospective Studies; Statistics, Nonparametric

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

Co-existence of obesity and type 2 DM exacerbates metabolic and other remediable health consequences further. Various pharmacological therapies have been adopted when changing of lifestyle fail to achieve target glycaemic control. Our objective is to find out whether Orlistat can reduce both weight and need for oral hypoglycaemic agent (OHA) and improves glycaemic status,lipid disorders, blood pressure in Bangladesh type 2 DM with obesity. In this center, open-label, randomized, controlled pilot trial 36 type 2 patients with obesity were enrolled. All patients aged 40-65 years had BMI >25 kg/m2 taking sulfonylureas and hypocalorie diet. Twenty one randomly cases were treated with orlistat 120 mg three times daily for 6 months and 15 without orlistat as control. Body weight, waist circumferances, fasting blood sugar, HbAlc,serum lipids, blood pressure and dose of drugs were monitored at 0,12, 24 weeks. After 6 months, orlistat group showed non-significant weight loss than control group (3.95% vs 1.42% from base lines), but showed significant reduction of waist circumference (6 % vs 0.63 %, p<0.01 vs p>0.05 from base line). Orlistat group had significant improvement in glycaemic status (HbA1c changes: 22.37% vs 13.38%, p<0.001 vs p>0.05 and FBS changes: 21.76% vs 22.95%, p<0.01vs p<0.05). Lipid profile had reduced significantly from base lines (Chol: 19.31% vs 9.12%,p<0.001vs >0.05; LDL Chol: 24.99% vs 19.09%, p<0.001 vs p<0.01; Triglyceride: 34.48% vs 12.61%, p<0.001 vs p>0.05). Diastolic pressure had improved significantly in orlistat group (6.73% vs 3.70%, p<0.01 vs >0.05). Reduction of OHA doses were found in both groups. Thus orlistat can be used as an adjuvant therapy with other OHA in managing glycaemic control, lipid profiles and blood pressure.

Topics: Adult; Aged; Bangladesh; Case-Control Studies; Chemotherapy, Adjuvant; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Lactones; Lipase; Middle Aged; Obesity; Orlistat; Sulfonylurea Compounds; Treatment Outcome

To investigate the efficacy and tolerability of orlistat in obese adolescents, a prospective, open-label, randomised, controlled pilot trial was performed. A total of 22 adolescents with exogeneous obesity were started on orlistat (120 mg tid) and a daily multivitamin preparation in addition to conventional treatment which included nutritional and lifestyle modification programmes. The control group consisted of 20 obese adolescents who had similar duration of follow-up under conventional treatment alone. Of the 22 patients, 7 dropped out within the 1st month of the trial due to side-effects attributable to orlistat. The remaining 15 patients on orlistat were followed for 5-15 months (average duration of treatment 11.7 +/- 3.7 months). The control group was similar in age, sex, and duration of follow-up (10.2 +/- 3.7 months, range 6-17 months) to the orlistat group. Compared to initial body weight, patients in the orlistat group lost -6.27 +/- 5.4 kg, whereas those in the control group gained 4.16 +/- 6.45 kg (P < 0.001) during the study period. Patients in the orlistat group lost -7.65% +/- 6.5% of their initial body weight, whereas, those of the control group gained 5.7% +/- 8.3% (P < 0.001). The body mass index decreased in the orlistat group by -4.09 +/- 2.9 kg/m2 while it increased by + 0.11 +/- 2.49 kg/m2 in the control group (P < 0.001). Mild gastrointestinal complaints (frequent stools) were experienced by all patients in the orlistat group.. Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents; however, gastrointestinal side-effects limit its usefulness in almost one in three adolescents.

Topics: Adolescent; Anti-Obesity Agents; Body Mass Index; Caloric Restriction; Child; Combined Modality Therapy; Exercise; Fecal Incontinence; Female; Humans; Lactones; Life Style; Lipase; Male; Obesity; Orlistat; Pilot Projects; Prospective Studies; Treatment Outcome; Vitamins

Metabolic syndrome (MetSyn) is associated with a marked increase in the risk of cardiovascular disease, especially in patients with type 2 diabetes mellitus (DM).. To investigate the effect of orlistat plus hypocaloric diet (HCD) vs HCD alone on the cardiovascular risk profile in patients with both MetSyn (National Cholesterol Educational Program--NCEP--Adult Treatment Panel III definition) and type 2 DM.. This was a prospective, multicentre, open-label, randomized, controlled study. One hundred and twenty-six patients, free of cardiovascular disease at baseline, were included in the final analysis. Ninety-four (73%) patients were treated with orlistat (360 mg/day) and HCD for a 6-month period, while 34 (27%) were on HCD alone. Analysis of covariance was used to assess differences between the treatment groups over time.. Components of the MetSyn criteria assessed were: waist circumference; systolic and diastolic blood pressure; fasting glucose, triglycerides; high-density lipoprotein cholesterol (HDL-C) plus body mass index; glycosylated haemoglobin (HbA1C); homeostasis model for assessment of insulin resistance (HOMA) index; and total and low-density lipoprotein cholesterol (LDL-C).. By protocol, all patients had MetSyn at baseline. After a 6 month treatment period there were significant differences between the orlistat plus HCD vs the HCD-alone groups in body weight (p = 0.0001), waist circumference (p < 0.0001), fasting glucose (p < 0.0001), HbA(1C) (p < 0.0001), systolic blood pressure (p = 0.024), total cholesterol (p < 0.0001), LDL-C (p = 0.034), and HOMA index (p = 0.022), while there were no significant differences in triglycerides and HDL-C. Orlistat was well tolerated. By the end of the study, 65% of the patients on orlistat plus HCD were still meeting the MetSyn criteria and 41% had four to five MetSyn components vs 91% (p < 0.0001) and 53% (p = 0.017), respectively, of those on HCD alone.. Orlistat plus HCD favourably modified several cardiovascular risk factors in patients with both MetSyn and type 2 DM. These effects might partly offset the excess cardiovascular risk and improve outcome in this patient population.

Topics: Anti-Obesity Agents; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Lactones; Lipase; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Risk Factors

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

The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a standardized diet, comparing the action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on anthropometric measurements, blood pressure (BP), and lipid profile.. This was a 1-year, randomized, double-blind, placebo-controlled trial. The patients were prescribed a controlled-energy diet and were randomly allocated to receive placebo, orlistat 120 mg TID (O group), fluvastatin 80 mg/d (F group), or olistat 120 mg TID with fluvastatin 80 mg/d (OF group). Clinical measurements (body weight, body mass index [BMI], waist circumference, and BP) and lipid profile assessment (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TGs]) were performed at baseline and after 6 months and 1 year of treatment.. The study included 99 obese patients with hypercholesterolemia (48 men and 51 women; mean [SD] age, 51 [9] years). There were no significant differences between groups in baseline demographic, BP, or plasma lipid values. Three patients dropped out (2 women in the O group and 1 man in the OF group) due to adverse events related to orlistat treatment, including gastrointestinal events (oily spotting and fecal urgency). Ninety-six patients completed the study. There were significant differences from baseline (mean [SD]) in BMI, waist circumference reduction (WCR), and body weight loss (BWL) at 6 months in the OF group (29.9 [1.1] kg/m(2), 2.7 [0.8] cm, and 7.4 [0.9] kg, respectively; all P < 0.05), and BMI, WCR, and BWL at 1 year in the O group (29.0 [1.0] kg/m(2), 3.0 [1.0] cm, and 8.6 [1.0] kg, respectively; all P < 0.02), the F group (29.3 [1.6] kg/m(2), 2.4 [1.0] cm, and 8/0 [1.0] kg, respectively; all P < 0.05), and the OF group (28.4 [0.6] kg/m(2), 4.0 [0.6] cm, and 11.4 [1.0] kg, respectively; all P < 0.01). Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups (all P < 0.05) and the OF group (both P < 0.01). At 6 months, there were significant reductions from baseline in TC and LDL-C in the F group (both P < 0.05) and in TC, LDL-C, and TGs in the OF group (P < 0.02, P < 0.02, and P < 0.05, respectively), as well as a significant increase in HDL-C in the OF group (P < 0.02). At 1 year, there were significant reduction from baseline in TC in the O, F, and OF groups (P < 0.05 and P < 0.01, respectively), LDL-C (P < 0.05, P < 0.02, and P < 0.01, respectively), and TGs (P < 0.02, P < 0.05, and P < 0.02, respectively). Also at 1 year, HDL-C was significantly higher than baseline in the F and OF groups (P < 0.02 and P < 0.01, respectively).. Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments.

Topics: Anthropometry; Anti-Obesity Agents; Blood Pressure; Diet, Reducing; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome

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

Orlistat is a gastrointestinal lipase inhibitor used to reduce dietary fat absorption and could be used to treat overweight and obesity in adolescents. The primary objective was to assess whether orlistat has an effect on the physiologic balance of three macrominerals (calcium, phosphorus and magnesium) and three microminerals (iron, zinc and copper).. This was a 21-day, double-blind, randomized, parallel-group, placebo-controlled mineral balance study conducted in adolescent obese volunteers (BMI >or=85th percentile, adjusted for age and gender). Subjects were maintained on a hypocaloric diet with a normal daily mineral content in both treatment groups and received oral treatment with orlistat 120 mg (n = 16) or placebo (n = 16) three times daily for 21 days. Following a 14-day equilibration period, balances for calcium, phosphorus, magnesium, iron, copper and zinc were measured for days 15-21. Serum and urine electrolytes were also measured at baseline and at the end of treatment.. On average, orlistat inhibited dietary fat absorption by approximately 27%. This degree of dietary fat inhibition caused no significant changes in mineral balance between orlistat and placebo groups. In addition, serum and urine electrolytes (sodium and potassium) as well as urinary creatinine excretion were not affected by orlistat treatment. Orlistat was well tolerated; adverse events occurred mainly in the gastrointestinal tract and were of mild or moderate intensities.. Administration of orlistat had no significant effect on the balance of six selected minerals in adolescent obese patients.

Topics: Adolescent; Anti-Obesity Agents; Child; Dietary Fats; Double-Blind Method; Electrolytes; Enzyme Inhibitors; Feces; Female; Gastrointestinal Diseases; Humans; Intestinal Absorption; Lactones; Male; Minerals; Obesity; Orlistat

Weight gain is a common side effect associated with antidepressant, anxiolytic, and antipsychotic drug use. Obesity is a risk factor for several other disorders, including hypertension, diabetes, and coronary artery disease. To date, there have been few safe, well-tolerated, and effective pharmacological agents available to alleviate weight gain in general, and virtually no studies specific to psychiatric drug-induced weight gain. This case series looks at the use of orlistat, a reversible inhibitor of lipases approved by the US Food and Drug Administration for obesity management, naturalistically in 13 patients with weight gain secondary to psychotropic drug use. The results showed that orlistat, administered in 3 daily doses with meals, was safe, well-tolerated, and effective, resulting in an average weight loss of 35% during an acute treatment period of about 3 months.

Topics: Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Psychotropic Drugs; Treatment Outcome; Weight Gain

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

Recent studies indicate that abdominal fat accumulation is related to impaired endothelial function in young healthy volunteers. The aim of this study was to determine the acute effect of gastrointestinal lipase inhibitor on brachial flow-mediated vasodilatation and hemodynamic parameters in young obese women. The study population was composed of 42 female obese patients (mean age 29 +/- 4 years, age range between 18 and 34 years). Flow-mediated endothelial-dependent vasodilatation was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Brachial artery diameter (3.46 +/- 0.72 mm to 3.82 +/- 0.84 mm) and flow-mediated vasodilation (7.6 +/- 0.8% to 9.8 +/- 1.6%) changed significantly after 12 weeks of therapy (p < 0.001). Brachial artery flow was not changed (124 +/- 92 ml/min to 148 +/- 14 ml/min, p > 0.05). The results of this study demonstrate that orlistat improved endothelial function, weight, body mass index and systolic and diastolic blood pressure in young women.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Brachial Artery; Cholesterol; Endothelium, Vascular; Female; Heart Rate; Humans; Lactones; Obesity; Orlistat; Triglycerides; Vasodilation

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

Orlistat, a lipase inhibitor, strongly inhibits the activities of all gastric/pancreatic lipases except pancreatic phospholipase A(2)in vitro. In clinical use, for obesity treatment, it induces a variable degree of weight loss and steatorrhoéa. The aim of this study was to examine the degree of in vivo inhibition of individual gastric/pancreatic lipases by Orlistat in man, when given as a capsule or mixed into a test meal in the form of an optimal substrate for the lipases.. Twelve male volunteers were intubated twice with a triple lumen nasal-gastric-duodenal tube and were given a balanced test meal with or without 60 mg Orlistat. Three conditions were compared: (a) Orlistat given as a capsule with the meal, (b) Orlistat mixed into the test meal before ingestion, and (c) test meal without Orlistat. Samples were collected at six 30 min intervals, from stomach, mid-duodenum, and ligament of TreitY. Activities and immune-reactive masses of gastric lipase, pancreatic lipase, carboxyl ester lipase, colipase, and mass of non-polar lipid classes were determined.. In vivo effects on the enzyme activities were more pronounced when Orlistat was mixed with the meal than when given as a capsule (7%, 10%, 1% vs 49%, 54%, 34% of normal activity), respectively. Despite efficient inhibition of the lipases, an extensive hydrolysis of the emulsified lipids of the test meal occurred. Orlistat did not affect the immune-reactive amounts of lipases.. Orlistat causes a pronounced in vivo inhibition of gastric and pancreatic lipases in humans. The mixing with the substrate and the fact that little residual lipase activity is necessary to hydrolyse optimally emulsified lipids are likely to be limiting factors for the effect of the drug in clinical practice.

Topics: Adult; Anti-Obesity Agents; Area Under Curve; Enzyme-Linked Immunosorbent Assay; Gastric Juice; Humans; Intestine, Small; Lactones; Lipase; Lipid Metabolism; Male; Middle Aged; Obesity; Orlistat; Pancreatic Juice; Radioimmunoassay; Stomach

To assess the long-term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes.. This was a multicentre, randomized, placebo-controlled study with a 4-week placebo plus diet lead-in period and a 48-week, double-blind treatment period. Overweight or obese adults [body mass index (BMI) >or= 28 kg/m2] with HbA1c of 6.5-11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low-calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug-naïve).. After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (-5.4% vs. -3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of >or= 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo-treated patients in HbA1c (-0.9% vs. -0.4%; p < 0.001), fasting glucose (-1.6 vs.-0.7 mmol/l; p = 0.004) and post-prandial glucose (-1.8 vs. -0.5 mmol/l; p = 0.003). In addition, orlistat-treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat.. Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Risk Factors

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

Post-prandial lipaemia is prolonged and exaggerated in patients with Type 2 diabetes mellitus, with an accumulation of atherogenic triglyceride-rich lipoprotein remnants. We postulate that orlistat, a gastrointestinal lipase inhibitor, may cause changes in post-prandial lipoprotein metabolism by reducing dietary triglyceride absorption.. The acute effect of a single dose of 120 mg orlistat on post-prandial glucose, lipids, remnant lipoproteins and free fatty acids (FFA) was evaluated in a randomized, double-blind, placebo-controlled cross-over study of 63 overweight patients with Type 2 diabetes mellitus (body mass index 30.4 +/- 3.8 kg/m2). Either a single dose of orlistat or placebo was given before a standard mixed meal containing 70 g of fat and plasma triglyceride (TG), remnant-like particles cholesterol (RLP-C) and FFA were sampled at 2-h intervals for 8 h. RLP-C was measured by an immunoseparation assay and FFA by an enzymatic colorimetric method.. The concentrations of plasma TG (P < 0.0001), RLP-C (P = 0.003), and FFA (P < 0.0001) were significantly lower at 2 h after orlistat compared with placebo. Both plasma RLP-C (P = 0.04) and FFA (P < 0.0001) remained lower after orlistat than placebo at 4 h. The incremental area under the curve (iAUC) above baseline fasting level for both TG and RLP-C was significantly more reduced after orlistat than placebo (iAUC-TG 5.8 (3.7-8.2) mmol/l x h-1 vs. 5.7 (4.1-10.9), respectively, P = 0.04; iAUC-RLP-C: 0.53 (0.23-1.04) mmol/l x h-1 vs. 0.56 (0.35-1.40), respectively, P = 0.02). The test meal was well tolerated by all subjects, with only three subjects reporting faecal urgency after orlistat.. Orlistat has a beneficial effect on post-prandial lipaemia in overweight Type 2 diabetic patients and lowers plasma TG, RLP-C and FFA in the early post-prandial period.

Topics: Adult; Anti-Obesity Agents; Cholesterol; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats; Double-Blind Method; Enzyme Inhibitors; Fatty Acids, Nonesterified; Female; Humans; Hyperlipidemias; Lactones; Lipase; Lipoproteins; Male; Middle Aged; Obesity; Orlistat; Postprandial Period; Triglycerides

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

Topics: Adult; Anti-Obesity Agents; Body Constitution; Body Mass Index; Cardiovascular Diseases; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Risk Factors

In the present study, we investigated the effects of a 6-month treatment with orlistat on body weight and lipid profile in 27 overweight women (mean body mass index [BMI]: 27.5 kg/m2; median age: 38.4 years) with mild hypercholesterolemia (total cholesterol: 225 mg/dl; low-density lipoprotein cholesterol [LDL-C]: 162 mg/dl). Orlistat was administered three times per day in conjunction with a hypocaloric diet After 6 months of treatment, body weight decreased by 17.71% and BMI decreased by 18.54%, whereas there was a significant (p < 0.01) improvement in serum lipid levels (total cholesterol: -25.33% LDL-C: -30.86%, high-density lipoprotein cholesterol: +9.37%, triglycerides: -35.97%). In conclusion, orlistat in combination with a low-energy diet seems to have a beneficial effect on body weight and lipid profile in overweight women with mild hypercholesterolemia.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Cholesterol, LDL; Diet, Reducing; Female; Humans; Hypercholesterolemia; Lactones; Lipoproteins, HDL; Middle Aged; Obesity; Orlistat; Treatment Outcome; Triglycerides

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 efficiency of 6-month therapy with xenical (gastrointestinal lipase inhibitor) in combination with diet in patients with stable angina pectoris associated with obesity and hyperlipemia.. An open comparative randomized study of the efficiency of xenical in combination with diet was carried out in patients with stable angina pectoris concomitant with obesity and hyperlipemia. Thirty coronary patients aged 45-65 years with stable angina of effort (functional class I-II) with body weight index 28.1-45.6 kg/m2 (mean 33.5 kg/m2) were examined. All patients presented with dyslipemia (low density lipoprotein (LDL) cholesterol more than 4.14 mmol/liter, triglycerides (TG) more than 2.2 mmol/liter). Controls (n = 15) were treated with diets alone for 6 months. In the main group diets were supplemented by xenical in a dose of 360 mg/day.. Body weight index decreased in both groups (by 9.9% in the main group and by 4.2% in the control). Body weight stabilization during 6 months of treatment and the fact that it was slow and gradual were essential. In patients treated with xenical total cholesterol level decreased by 10.9% and of LDL cholesterol by 12.2% after 6 months (p < 0.05). Changes in the levels of high density lipoprotein cholesterol and TG were insignificant. The drug did not affect the incidence of angina attacks and improved exercise tolerance after 6-month therapy. Blood biochemistry (transaminases, alkaline phosphatase, glucose, and creatinine) changed negligibly. No side effects were observed; all patients received a complete 6-month course.. The results confirm that xenical (orlistat) can be used for long therapy of patients with stable angina of effort concomitant with obesity and hyperlipemia.

Topics: Aged; Angina Pectoris; Anti-Obesity Agents; Anticholesteremic Agents; Exercise Test; Female; Humans; Hyperlipidemias; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat

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

The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients.. A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes.. After 1 year of treatment, mean (+/-SE) weight loss was greater in the orlistat than in the placebo group (-4.6 +/- 0.3% vs. -1.7 +/- 0.3% of baseline wt, P < 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA(1c), adjusted for changes in metformin and sulfonylurea therapy (-0.90 +/- 0.08 vs. -0.61 +/- 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA(1c) of > or = 0.5 and > or = 1.0% (both P < 0.01); and a greater reduction in fasting serum glucose (-2.0 +/- 0.2 vs. -0.7 +/- 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P < 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P < 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P < 0.05).. Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Humans; Hypoglycemic Agents; Lactones; Lipoproteins; Metformin; Middle Aged; Missouri; Obesity; Orlistat; Placebos; Racial Groups

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 is a gastrointestinal lipase inhibitor that is used to reduce dietary fat absorption and to enhance weight loss in subjects consuming a hypocaloric diet. To assess whether orlistat has an effect on the metabolism of six minerals, a 21-d, double-blind, randomized, parallel-group, placebo-controlled mineral balance study was conducted in obese (body mass index > 30 kg/m(2)) men. Subjects consumed a hypocaloric diet with a constant daily mineral content and received daily oral treatment with orlistat (120 mg three times daily) (n = 14) or placebo (three times daily) (n = 14) for 21 d. After a 14-d equilibration period, calcium, phosphorus, magnesium, iron, copper and zinc balances were assessed for d 15-21. In addition, the effect of diet and orlistat treatment on bone metabolism was estimated from measurement of biomarkers of bone formation and bone resorption. Serum and urine electrolytes were also measured at baseline and at the end of treatment. Orlistat inhibited fat absorption by approximately 33% (P < 0.05). There were no significant differences in mineral apparent absorption, urinary mineral loss or mineral balance between the orlistat and placebo groups. Markers of bone turnover and serum and urine electrolytes did not differ between the orlistat and placebo groups. Orlistat was well tolerated; adverse events were of mild or moderate intensity, and the majority of these events were unrelated or remotely related to study treatment. In obese men consuming a hypocaloric diet, the administration of orlistat had no significant effect on the balance of six selected minerals. In addition, biomarkers of bone turnover, as well as serum and urine electrolytes, were not affected by orlistat treatment.

Topics: Adult; Anti-Obesity Agents; Bone and Bones; Dietary Fats; Double-Blind Method; Electrolytes; Energy Intake; Enzyme Inhibitors; Feces; Gastrointestinal Diseases; Humans; Lactones; Male; Minerals; Obesity; Orlistat

The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal.

Topics: Adult; Anti-Obesity Agents; Dietary Fats; Duodenogastric Reflux; Duodenum; Female; Gastric Juice; Gastric Mucosa; Humans; In Vitro Techniques; Intubation, Gastrointestinal; Lactones; Lipase; Lipolysis; Male; Middle Aged; Obesity; Orlistat; Pancreas; Pancreatic Juice

To study the effect of weight loss and subsequent weight maintenance or weight regain on the activities of FVII and plasminogen activator inhibitor 1 (PAI-1) and the concentration of fibrinogen over 12 months in obese women consuming a hypoenergetic, low-fat diet with or without orlistat. In addition, the relation between the changes of the activities of PAI-1 and FVII with the changes of other cardiovascular risk factors were examined.. Design-a 12-month randomized double-blind weight reduction trial of placebo and orlistat. Subjects-51 healthy obese women (age 44+/-0.7 y, BMI 36.2+/-0.5 kg/m(2), mean+/-s.e.m.) Treatment-the participants were on a hypoenergetic diet (-600 kcal daily). The diet was adjusted for actual body weight (-300 kcal) at 6 months. Women were randomized to receive either orlistat 120 mg three times daily (n=25) or placebo three times daily (n=26) for 12 months according to a double-blind protocol after a 1 month run-in period. Measurements-changes of body weight, body composition, haemostatic and other cardiovascular risk factors were measured at 3-6 month intervals. The activity of plasma PAI-1 was measured by a chromogenic method, fibrinogen by the PT-derived method and the activity of FVII by the one-stage method.. The changes in body weight between orlistat and placebo groups were not statistically significantly different. Orlistat did not influence haemostatic factors beyond its effect on weight loss. Therefore, the results of the orlistat and placebo groups were pooled. The average weight loss at 3, 6 and 12 months was 7.6, 9.5 and 10.0 kg, respectively (P<0.001). Between 6 and 12 months, 35% of women regained weight, 24% had stable weight and 41% continued to lose weight. No changes in the mean plasma fibrinogen concentration were observed at any time point during the trial. During the first 3 months the activities of PAI-1 and FVII decreased. The decline depended on the magnitude of weight loss. Between months 6 and 12 the changes of PAI-1 and FVII activities paralleled the changes of body weight. The activities rose with weight rebound but remained below the 6-month values if weight loss was sustained or continued. The changes of serum insulin were significantly correlated with the changes of both PAI-1 and FVII at 6 months and with PAI-1 at 12 months.. The maintenance of modest weight loss is associated with long-term benefits in PAI-1 and FVII in obese women. The change of serum insulin is associated with the changes of PAI-1 activities. Fibrinogen is not affected by modest weight loss.

Topics: Adult; Anti-Obesity Agents; Antigens; Blood Coagulation; Body Weight; Diet, Reducing; Factor VII; Female; Fibrinogen; Fibrinolysis; Humans; Insulin; Lactones; Obesity; Orlistat; Plasminogen Activator Inhibitor 1

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

This placebo-controlled open study was designed to test the hypothesis that most of the gastrointestinal (GI) side events induced by treatment of obese patients with orlistat (a gastrointestinal lipase inhibitor) could be prevented or ameliorated by concomitant use of natural fibers (psyllium mucilloid).. Two groups of obese women (BMI>27 kg/m(2)) were treated with orlistat 120 mg three times a day. One group (A, n=30) was randomized to receive orlistat and, approximately 6.0 g of orange-flavored psyllium mucilloid dissolved in water and the other group (B, n=30) received orlistat and orange-flavored placebo. At the end of 30 days and 2 weeks of washout, group A switched to placebo and group B received psyllium while continuing orlistat three times a day.. Sixty professional women, more than 21-y-old with a body mass index (BMI) between 27.3 and 48.0 kg/m(2), who were not receiving any other medication.. Assessments included weekly visits to attending physician, filling a form in which GI events were recorded, monthly measurements of body weight, blood pressure and serum lipids. The frequency and severity of GI events were evaluated by a score system, based on information provided by the patients.. Both groups A and B significantly lost (P<0.01) weight after 60 days of orlistat (A=96.8 to 94.9 kg and B=98.7 to 96.5 kg). Similarly, BMI values declined significantly in both groups. While in the psyllium plus orlistat group (group A) the mean +/-s.e.m. of the scores reflecting GI events was 13.0+/-1.8, the placebo plus orlistat group (B) had a value of 35.9+/-2.7 (P<0.01). When the reverse situation was instituted the placebo and orlistat group presented a mean score of 36.1+/-3.6 and the psyllium plus orlistat a mean score of 8.9+/-1.5 (P<0.01).. Psyllium hydrophilic mucilloid concomitantly prescribed to obese patients receiving 120 mg of orlistat three times a day is an effective and safe adjunct therapy that is helpful in controlling the GI side effects of this pancreatic lipase inhibitor.

Topics: Adult; Anti-Obesity Agents; Cross-Over Studies; Digestive System; Female; Humans; Lactones; Obesity; Orlistat; Psyllium

Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration.. Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of intravenous ([(2)H(6)] cholesterol) and oral ([(2)H(5)] cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption.. In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01).. These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.

Topics: Adult; Anti-Obesity Agents; Cholesterol, Dietary; Cholesterol, LDL; Cross-Over Studies; Enzyme Inhibitors; Female; Humans; Intestinal Absorption; Intestines; Isotope Labeling; Lactones; Lipase; Male; Obesity; Orlistat; Prospective Studies; Reproducibility of Results

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

257 patients from 33 centres were involved in a six-month study, the aim of which was to assess the effect of orlistat together with a diet. The authors examined how the treatment effected the anthropometrical and lipid parameters, extending the study to the aspect of paraoxonase activity in case of 25 patients. 44 patients dropped out during the study period due to the lack of sufficient diet compliance, whereas 3 patients had to stop the therapy because of the adverse event of flatus with discharge. On the average, the body mass of the patients decreased from 100.8 +/- 18.9 to 91.3 +/- 18.6 kg, i.e. by 9.5 kgs, while their BMI was reduced from 36.1 +/- 5.6 to 32.5 +/- 5.2 kg/m2 and the circumference of the waist changing from 119.1 +/- 20 to 108.3 +/- 15.1 cm, i.e. by 10.8 cms. The blood sugar level significantly decreased from 5.7 to 5.4, while the cholesterol concentration significantly dropped from 5.9 to 5.5, the triglyceride level being reduced from 2.4 to 2.1 mmol/l and blood pressure falling significantly from 136.6/86.9 to 129.9/81.6. All the above changes showed a significant decrease. However, the HDL-cholesterol level did not change. The serum paraoxonase activity significantly increased (143 +/- 49 vs 166 +/- 43 UL) along with the standardised values for HDL (PON/HDL), even compared to the control diet group. From the above results it may be concluded that orlistat tends to have an antioxidant effect.

Topics: Abdomen; Adult; Aged; Anti-Obesity Agents; Aryldialkylphosphatase; Body Mass Index; Body Weight; Cholesterol; Diet, Reducing; Enzyme Inhibitors; Esterases; Female; Humans; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Time Factors; Treatment Outcome; Triglycerides

To assess the efficacy and tolerability of orlistat (Xenical) in producing and maintaining weight loss over a 12-month period.. Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months.. Five centres in the UK.. 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74-144 kg).. All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily.. Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and beta carotene.. Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P < 0.05), and 28% and 17%, respectively (P = 0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P < 0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein: high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and beta carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P < 0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks.. Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (> or = 5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.

Topics: Adult; Aged; Anthropometry; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Weight; Digestive System; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Insulin; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Placebos

To study the composition of fat intake and fat-rich meals consumed during a trial in which obese subjects were treated with a lipase-inhibitor or placebo, with emphasis on food choices and eating hours.. Patients were instructed to record all food and drink taken for four days prior to each dietician visit. The food diaries from all scheduled 15 treatment visits were analysed for nutritional content and composition and for temporal distribution. All meals containing 25 g of fat were defined as fat-rich.. Twenty-eight women and six men, mean age 45.2 +/- 10.9 (SD) years with a mean body mass index of 37.3 +/- 3.3 (SD) kg m-2 at the beginning of the study.. Fat intake, both as absolute weight and as energy % was generally higher in the placebo group but no significant trend over time could be seen. Fat rich meals were increased by 59% towards the end of the study. Most fat rich meals were eaten at lunch and dinner. Cooking fat, fatty sauces, meat dishes and cheese contributed to the major proportion of fat, both for placebo and drug treated subjects. No major changes were seen in food choice over time.. A lipase inhibitor may affect the amount of fat ingested but does not seem to change major sources of fat. The typical fat-rich meal consumed by these subjects was a meat dish, consumed in the evening.

Topics: Analysis of Variance; Anti-Obesity Agents; Behavior Therapy; Diet Records; Diet, Reducing; Dietary Fats; Double-Blind Method; Energy Intake; Female; Food Preferences; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Sweden; Treatment Outcome

To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk.. After screening, patients entered a two-week single-blind placebo lead-in period, during which they followed a mildly hypocaloric diet, before being randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years.. The study was conducted at 33 primary care centres in Sweden.. A total of 382 obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186).. Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c.. After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly more orlistat-treated patients than placebo recipients maintained weight loss of > or = 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with significantly greater improvements than placebo in total serum cholesterol (- 3.3% vs. -0.5%; P < 0.05), LDL-cholesterol (- 7.0% vs. -1.1%; P < 0.05), fasting glucose (5.1% vs. -0.1%; P < 0.01) and HbA1c (- 2.7% vs. -0.5%; P < 0.05). Similar results were reported for the subgroup of patients with type 2 diabetes. Orlistat was well tolerated.. Treatment with orlistat in conjunction with diet promotes significantly greater weight loss and cardiovascular risk factor reduction than diet alone amongst obese patients at high risk of future coronary events.

Topics: Adult; Aged; Analysis of Variance; Anti-Obesity Agents; Cardiovascular Diseases; Chi-Square Distribution; Diet, Reducing; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Statistics, Nonparametric; Sweden

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

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

We undertook a randomised controlled trial to assess the efficacy and tolerance 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: Adolescent; Anti-Obesity Agents; Biomarkers; Body Mass Index; Cholesterol; Cholesterol, LDL; Diet, Fat-Restricted; Double-Blind Method; Female; Humans; Lactones; Lipase; Male; Obesity; Orlistat; Secondary Prevention; Weight Gain

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

Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double-blind, placebo-controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (< 10 ng/mL or 0.02 microM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.

Topics: Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Enzyme Inhibitors; Gastrointestinal Diseases; Humans; Lactones; Lipase; Obesity; Orlistat; Time Factors; Treatment Outcome

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

To determine whether there are any changes in the fatty acid composition of serum triglycerides, cholesterol esters, and phospholipids induced by administration of orlistat three times a day compared with placebo as combined with a low-fat hypocaloric diet.. After 4 weeks of placebo administration, 75 obese subjects were randomized to receive either one capsule (120 mg) of orlistat or placebo three times a day with meals for 1 year in conjunction with a nutritionally balanced hypocaloric diet. Food records were kept to estimate the nutrient intake. The fatty acid composition of serum lipids were analyzed with gas chromatograph. The molar percentage proportions of fatty acids in serum lipid fractions were calculated.. Compared with placebo, there was a significant decrease in the proportion of linoleic acid in triglycerides, cholesterol esters, and phospholipids in the orlistat group, even after the effect of the decrease in the linoleic acid dietary intake (percent of energy), weight change, and gender were taken into account. However, the use of orlistat explained only 9% to 13% of the decrease in the proportion of linoleic acid in serum cholesterol esters, triglycerides, and phospholipids.. The long-term treatment with orlistat may result in a small decline in the proportion of diet-derived fatty acids in serum lipid fractions when used in conjunction with low-fat diet.

Topics: Adult; Anti-Obesity Agents; Fatty Acids; Female; Humans; Lactones; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat

To determine the weight-reducing efficacy of orlistat, a novel gastrointestinal lipase inhibitor, and to define the optimal dosage regimen and establish the tolerability of the drug when used for a 6-month treatment period.. The study was a multicentre randomised, double-blind, parallel group in design and involved 676 obese male and female subjects aged at least 18 years with a body mass index between 28 and 43 kg x m(-2) Following a 5-week placebo run-in period, subjects were randomised to receive orlistat 30 mg, 60 mg, 120 mg, 240 mg or matching placebo three times a day (tid) for 24 weeks during meals. Patients were maintained on a mildly hypocaloric diet throughout the study period. The primary efficacy parameter was body weight change over time.. Orlistat resulted in a significantly greater mean loss of body weight than observed in the placebo group. In absolute terms, mean weight loss was greatest in the 120 mg group (9.8%). More orlistat- than placebo-treated patients lost > 10% of initial body weight (37% of the 120 mg group vs 19% of the placebo group). Orlistat was well tolerated. Predictably, in view of its known pharmacological effects, more orlistat-treated patients experienced gastrointestinal events. Mean levels of vitamins A, D and E, and beta-carotene remained within the clinical reference ranges in all treatment groups and rarely required supplementation. After 24 weeks, plasma concentrations of orlistat were either non-measurable or detected at the assay's limit of quantitation.. Orlistat treatment results in a dose-dependent reduction in body weight in obese subjects and is well tolerated. Orlistat 120 mg tid represents the optimal dosage regimen.

Topics: Adult; Body Weight; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat

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

Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications.. In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured.. After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.. Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.

Topics: Adult; Apolipoproteins; Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Enzyme Inhibitors; Female; Glycated Hemoglobin; Humans; Lactones; Lipase; Lipoproteins; Male; Middle Aged; Obesity; Orlistat; Placebos; Triglycerides

Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.

Topics: Drug Tolerance; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat

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

This paper describes the methodology of a multicentre study designed to assess the efficacy and tolerability of orlistat 120 mg tid as therapy for inducing weight loss in excess of that achieved with a moderately calorie-restricted diet alone. The results from a single centre are presented to illustrate the nature of the response.. This was a double-blind, randomized, parallel-group, placebo-controlled multicentre study. A four-week, single-blind, placebo run-in period preceded a 52 week double-blind treatment period during which patients received either orlistat or placebo three times a day. At the start of the run-in period, all patients were placed on a diet containing approximately 30% of calories as fat and designed to cause an energy deficit of approximately 600 kcal/d.. Patients of either sex, more than 18 y of age, with a body mass index (BMI) between 30 and 43 kg/m2 were eligible for enrolment.. Efficacy assessments included: measurements of body weight; anthropometry; quality of life; blood pressure; serum lipids; fasting serum glucose and insulin. Safety assessments included: adverse events; vital signs; ECG; renal and gallbladder ultrasound; haematology; serum biochemistry.. In the single centre there was a reduction in body weight of 5.5 +/- 4.5 (s.d.) kg (5.7% reduction) in the placebo group and 8.6 +/- 5.4kg in the orlistat-treated group (8.4% reduction) by six months. Thereafter, the placebo group tended to relapse whereas the orlistat group maintained their loss (2.6% vs 8.4% reduction from initial value at 52 weeks). Total and LDL cholesterol fell by 0.05 mmol/l (1.6%) and 0.14 mmol/l (4.2%), respectively, in orlistat treated patients. The drop-out rate was 48% in the placebo group and 39% in the orlistat group. Intestinal symptoms related to orlistat were significantly increased compared to placebo but were well tolerated. Fat soluble vitamin levels remained within the normal range in the treatment group; the reduction seen in alpha-tocopherol levels in patients receiving orlistat was normalized by the decrease in plasma cholesterol concentrations. Beta-carotene and vitamin D concentrations also decreased in orlistat-treated patients.. This preliminary analysis suggests that orlistat, when used with a health-promoting low-fat and moderately energy-restricted diet, confers advantages in the long-term management of obesity.

Topics: Adult; Body Weight; Double-Blind Method; Energy Intake; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Risk Factors

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 determine the metabolic profile of minimally absorbed orlistat in obese/overweight patients, an open-label, single-dose study was performed in eight obese/overweight volunteers between 23 and 68 years of age. Each subject received a single oral dose of 360 mg orlistat containing approximately 400 muCi of 14C-labeled orlistat. Serial blood samples were collected at specified times over 10 hours after administration of orlistat for determination of total radioactivity, unchanged orlistat, and major metabolites in the plasma. Urine samples were collected over 24 hours and analyzed to evaluate the urinary recovery of total radioactivity and the profile of orlistat metabolites in the urine. In addition, all fecal samples were collected and analyzed for total radioactivity. Urinary and fecal recovery of the administered dose of total radioactivity were 1.13 +/- 0.50% (24-hour data only) and 96.4 +/- 18.1% (n = 7), respectively. Maximum observed concentration (Cmax) and time to Cmax (tmax) values of plasma total radioactivity were 150 +/- 51 ng.eq/mL and 6.8 +/- 1.5 hrs, respectively. All these parameters obtained in obese/ overweight subjects were similar to those reported previously in healthy subjects. On the basis of the area under the concentration-time curve from 0 to 10 hours (AUC0-10), two major metabolites comprise a total of approximately 42% of the total radioactivity in plasma. The primary metabolite (M1) has a short half-life (approximately 2 hours), whereas the secondary metabolite (M3) disappeared at a slower rate. No strikingly apparent difference in the urinary metabolic profile was observed between two gender groups. It is concluded that the disposition of orlistat appears to be similar between normal and obese/overweight subjects. Of the minimal fraction of the dose that was absorbed systemically, the presence of two major metabolites accounts for approximately 42%.

Topics: Absorption; Administration, Oral; Adult; Aged; Body Weight; Carbon Radioisotopes; Enzyme Inhibitors; Female; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat

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

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.

Topics: Body Composition; Catecholamines; Dietary Fats; Double-Blind Method; Energy Intake; Gastrointestinal Transit; Hormones; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lactones; Lipase; Obesity; Orlistat; Pancreatic Hormones; Thyroid Hormones; Treatment Outcome

Orlistat, an inhibitor of gastrointestinal lipases, limits the absorption of ingested fat and could become a potential treatment for obesity. This analysis was performed to elucidate the relationship between orlistat dose and intensity of inhibition of dietary fat absorption (assessed by measuring fecal fat excretion). In 11 phase I double-blind, placebo-controlled, parallel-group randomized studies, a total of 171 subjects received oral daily doses that ranged from 30 to 1200 mg orlistat or matching placebo three times a day for 9 to 10 days. The results of the daily mean fecal fat excretion percentage (relative to ingested fat) were correlated to the orlistat daily dose. A simple maximum-effect model that included a basal value was used to fit the dose-response relationship for all evaluable subjects. The mean maximum percentage of ingested fat excreted in the feces was approximately 32% during orlistat administration compared with 5% during placebo administration. The orlistat daily dose that produced 50% of the maximum effect was 98 mg/day. The model-fitting suggests the existence of a steep portion of the dose-response curve up to approximately 400 mg/day, with a subsequent tendency to plateau at higher doses. Such an analysis was instrumental in identifying appropriate doses to be used in therapeutic trials for weight loss in obese patients.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Feces; Female; Humans; Lactones; Lipase; Lipid Metabolism; Male; Middle Aged; Obesity; Orlistat; Reference Values; Retrospective Studies

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

Obesity is a multi-factorial metabolic syndrome that increases the risk of cardiovascular diseases, diabetes, and cancer. We recently demonstrated the antiadipogenic efficacy of lutein using a 3 T3-L1 cell culture model. This study aimed to examine the antiobesity efficacy of lutein on high-fat (60% kcal fat) diet-induced C57BL/6J obese mice model. Lutein (300 and 500 μM), Orlistat (30 mg/kg body weight - positive control), and its combination (orlistat, 15 mg/kg body weight+lutein, 300 μM) were administered in high-fat diet (HFD)-fed mice every other day for 24 weeks. The effect on serum and hepatic lipid parameters was estimated using biochemical assay kits. The adipose tissue expression of adipocyte differentiation markers at gene and protein levels was analyzed by RT-PCR and western blotting, respectively. The results showed that lutein administration and drug significantly reduced epididymal and abdominal adipose tissue weights. Further, lutein reduced the serum cholesterol and LDL-C concentration compared to the HFD group. The HFD-induced elevation in the hepatic triglycerides and cholesterol levels were significantly blocked by lutein and its combination with the drug. Similarly, lutein and its drug combination efficiently lowered the HFD-mediated elevated blood glucose levels. Lutein downregulated the expression of CEBP-α, PPAR-γ, and FAS in the epididymal adipose tissue. Thus, supplementation of lutein may control diet-induced obesity and associated complications in the human population.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Cholesterol; Diet, High-Fat; Fatty Liver; Glucose Intolerance; Humans; Liver; Lutein; Mice; Mice, Inbred C57BL; Obesity; Orlistat

Pancreatic lipase (PL) is a key lipolytic enzyme in humans for the digestion and absorption of dietary fats. Thereby, PL is a well-recognized target in the management of obesity and its inhibition attracts the interest of researchers globally. The screening of new natural PL inhibitors as alternative strategy to the synthesis of chemical ones represents nowadays a hot topic in research. The main challenge in this matter is the lack of a universal analytical method allowing the monitoring of PL activity and the reliable quantification of lipid digestion products.. The (normal phase)-high-performance liquid chromatography-evaporative light scattering detector [(NP)-HPLC-ELSD] method proposed in this work represents a direct and rapid strategy to simultaneously quantify the products obtained from in vitro PL digestion. As one of the main novelties, the triacylglycerol (TAG) fraction from extra-virgin olive oil was selected as natural substrate. The PL activity was measured by monitoring the levels of remaining TAGs and formed free fatty acids (FFAs), using Orlistat as known inhibitor. The method validation confirmed the adequacy of the analytical method for quantitative purposes, showing high recovery percentage values (between 99% and 103%) and low relative standard deviation (RSD%) values (between 2% and 7%) for triolein and oleic acid standard solutions, as well as appreciably low limit of detection (LOD) and limit of quantification (LOQ) values (respectively 58 and 177 ng mL. The proposed innovative method reveals highly sensitive and simple to follow the fate of PL digestion, thus opening the way to further investigations in the research of new potentially anti-obesity compounds. © 2022 Society of Chemical Industry.

Topics: Chromatography, High Pressure Liquid; Humans; Lipase; Obesity; Oleic Acids; Orlistat; Triolein

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

Obesity is one of the foremost public health concerns. Human pancreatic lipase (hPL), a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, has been validated as an important therapeutic target for preventing and treating obesity. The serial dilution technique is commonly used to generate solutions with different concentrations and can be easily modified for drug screening. Conventional serial gradient dilution is often performed with tedious multiple manual pipetting steps, where it is difficult to precisely control fluidic volumes at low microliter levels. Herein, we presented a microfluidic SlipChip that enabled formation and manipulation of serial dilution array in an instrument-free manner. With simple slipping steps, the compound solution could be diluted to seven gradients with the dilution ratio of 1:1 and co-incubated with the enzyme (hPL)-substrate system for screening the anti-hPL potentials. To ensure complete mixing of solution and diluent during continuous dilution, we established a numerical simulation model and conducted an ink mixing experiment to determine the mixing time. Furthermore, we also demonstrated the serial dilution ability of the proposed SlipChip using standard fluorescent dye. As a proof of concept, we tested this microfluidic SlipChip using one marketed anti-obesity drug (Orlistat) and two natural products (1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) and sciadopitysin) with anti-hPL potentials. The IC

Topics: Humans; Indicator Dilution Techniques; Lipase; Microfluidics; Obesity; Orlistat; Proteins

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

Artemisia annua L., known as "sweet wormwood," is widely used in Egyptian folk medicine. Egyptians implement the aerial parts in the treatment of respiratory, digestive and sexual dysfunctions. However, the mechanism by which Artemisia annua improves testicular function is still being discovered.. This study aimed to evaluate the modulatory effects of the crude leaf extract of Artemisia annua (AAE) on a high-fat diet induced testicular dysfunction in rats and compare it with the antilipolytic drug Orlistat.. Forty adult rats were randomly classified and assigned to four groups. The first group typically consumed a balanced diet and served as a negative control (GP1). A high-fat diet-induced obesity was applied to the other three groups for 12 weeks. A positive control remained on HFD for another 8 weeks, which is GP2. Other groups were administered for 8 consecutive weeks either with Orlistat (50 mg/kg body weight) or AAE (100 mg/kg body weight), which have been defined as GP3 and GP4, respectively. Testosterone (TST), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the sera of all groups. In addition, the oxidant/antioxidant biomarkers such as protein carbonyl, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) activities, lactate dehydrogenase (LDH) and creatine kinase isoenzyme-B (CK-MB) were determined. An immunohistochemical stain with the apoptotic marker caspase-3 and the proliferating cell nuclear antigen (PCNA) were also investigated.. In the testes of the obese group, the results showed hormonal imbalance, an increase in oxidative stress biomarkers and apoptosis. In the group treated with orlistat (GP3), noticeably more perturbations were noted. The obese rats that had been treated with AAE (GP4) showed a significantly reduced level of oxidative stress, hormonal balance restoration and reduced apoptosis.. The crude leaf extract of A. annua is a potential herbal therapeutic for the treatment of obesity-related testicular dysfunction and the restoration of hormonal imbalance in obese rats.

Topics: Animals; Antioxidants; Artemisia annua; Biomarkers; Diet, High-Fat; Humans; Male; Obesity; Orlistat; Oxidative Stress; Plant Extracts; Rats; Spermatogenesis; Testicular Diseases; Testis

Obesity is currently regarded as a global concern, and the key objectives of the global health strategy include its prevention and control. Probiotic supplementation can help achieve these objectives. This study aimed to assess whether a probiotic strain

Topics: Animals; Diet, High-Fat; Lactobacillus; Lipids; Mice; Obesity; Orlistat; Probiotics; Rats; Rats, Sprague-Dawley

Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown.. To quantify cost-effectiveness of different antiobesity drugs available for pediatric use.. This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature.. Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis.. Incremental cost-effectiveness ratio.. Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY.. In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Topics: Adolescent; Anti-Obesity Agents; Child; Cost-Benefit Analysis; Female; Humans; Liraglutide; Male; Obesity; Obesity, Morbid; Orlistat; Phentermine; Topiramate

<b>Background and Objective:</b> Obesity is a global health epidemic associated with various health complications. This study investigates the potential effects of ethanolic fig leaf extract and orlistat on obesity, as well as their impact on kidney and liver function in a rat model, aiming to contribute to the development of strategies for managing obesity-related health issues. <b>Materials and Methods:</b> Forty male albino rats with hypercholesterolemia were divided into four groups: Group one served as a control and received a normal diet, group two was a control group that was fed a high-fat diet, group three received a high-fat diet with a daily force-fed ration of 3 g kg¹ b.wt., of fig leaves and group four received a high-fat diet along with daily administration of orlistat at 4 mg kg¹ b.wt. Blood samples were collected from all groups at baseline and after 30 days of treatment. <b>Results:</b> Rats in the high-fat diet group showed a significant increase in body weight by 49%, while rats treated with fig leaf extract showed a significant decrease in body weight by 18% (p<0 .01) and treatment with orlistat resulted in 12% elevation in body weight. Renal function markers creatinine and urea were decreased in the group treated with fig leaves. Liver enzymes AST, ALT and ALP decreased significantly in the group treated with fig leaves and orlistat. Albumin and globulin concentrations decreased more with fig leaf extract than with orlistat. <b>Conclusion:</b> Fig leaves and orlistat reduce body weight and improve kidney and liver function in hypercholesterolemic rats.

Topics: Animals; Body Weight; Ficus; Kidney; Liver; Male; Obesity; Orlistat; Plant Extracts; Rats

A new coronavirus pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been on the rise. This virus is fatal for broad groups of populations, including elderly, men, and patients with comorbidities among which obesity is a possible risk factor. The pathophysiologic connections between obesity/metainflammation and COVID-19 may be directly related to increasing soluble ACE2 (angiotensin-converting enzyme 2) levels which potentiate the viral entrance into the host cells, or indirectly related to dysregulation of immune system, microvascular injury and hypercoagulability. The SARS-CoV-2 S-glycoprotein interacts mainly with ACE2 or possibly DPP4 receptors to enter into the host cells. The host proteases, especially TMPRSS2 (transmembrane protease serine 2), support the fusion process and virus entry. While membranous ACE2 is considered a port of entry to the cell for SARSCoV- 2, it seems that soluble ACE2 retains its virus binding capability and enhances its entry into the cells. Interestingly, ACE2 on cell membrane may have protective roles by diminishing cytokine storm-related injuries to the organs. Applying medications that can reduce soluble ACE2 levels, antagonizing TMPRSS2 or blocking DPP4 can improve the outcomes of COVID-19. Metformin and statins through immunomodulatory activities, Orlistat by reducing viral replication, and thiazolidinediones by upregulating ACE2 expression have potential beneficial effects against COVID-19. However, the combination of dipeptidyl peptidase-4 (DPP4) inhibitors and spironolactone/ eplerenone seems to be more effective by reducing soluble ACE2 level, antagonizing TMPRSS2, maintaining ACE2 on cell membrane and reducing risk of viral entry into the cells.

Topics: Aged; Angiotensin-Converting Enzyme 2; COVID-19; Dipeptidyl Peptidase 4; Eplerenone; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metformin; Obesity; Orlistat; Peptidyl-Dipeptidase A; SARS-CoV-2; Spironolactone; Thiazolidinediones

Twenty-nine overweight/obese patients undergoing IVF/ICSI for the first time were treated with orlistat intervention (orlistat group). Another 29 patients with matched age and body mass index (BMI) were included in the control group at a ratio of 1:1. Clinical data of both groups were collected, and the clinical baseline data, IVF/ICSI cycle information and embryo transfer outcome were compared between groups by Student's. The 29 patients in the orlistat group completed 37 embryo transfer cycles, and the 29 subjects in the control group completed 38 embryo transfer cycles. There was no significant difference in the clinical baseline data or IVF/ICSI cycle data between the two groups (. Orlistat intervention for overweight/obese infertile women receiving IVF/ICSI treatment will increase the clinical pregnancy rate, without affecting the total amount of gonadotropins, ovarian stimulation time or the follicular output rate (FORT).

Topics: Female; Fertilization in Vitro; Humans; Infertility, Female; Obesity; Orlistat; Overweight; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic

Genetically modified probiotics have potential for use as a novel approach to express bioactive molecules for the treatment of obesity. The objective of the present study was to investigate the beneficial effect of genetically modified Escherichia coli Nissle 1917 (EcN-GM) in obese C57BL/6J mice.. After supplementation for 8 weeks, EcN-GM was associated with decreases in body weight gain, food intake, fat pad and liver weight, and alleviation hepatocyte steatosis in obese mice. EcN-GM also increased the level of GLP-1 in serum and alleviated leptin and insulin resistance. Moreover, supplementation with EcN-GM increased the α-diversity of the intestinal microbiota but did not significantly influence the relative abundance of Firmicutes and Bacteroidetes.. These results indicated that EcN-GM, a genetically modified E. coli strain, may be a potential therapeutic approach to treat obesity. The beneficial effect of EcN-GM may be independent of the alteration of the diversity and composition of the intestinal microbiota in obese mice.

Topics: Animals; Escherichia coli; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Orlistat; Probiotics

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 currently a global issue and is a major cause of the metabolic disorder, including dyslipidemia. However, currently approved treatments have various limitations including serious side effects, numerous contraindications, and lack of acceptance. Caulerpa racemosa, also referred as Sea grapes, is a seaweed known for its various benefits. C. racemosa extract has the potential to improve lipid profile and role as an anti-obese agent. In order to maximize its health benefits, C. racemosa was made using kombucha drink as a carrier medium. This study aims to assess the effect of Sea grapes kombucha drink on lipase activity in vitro and lipid profile in vivo.. A lipase inhibition test was carried out by incubating Sea grapes kombucha drink compared with orlistat as the control in porcine pancreatic lipase and p-nitrophenyl butyrate in reaction buffer. A total of four groups were made, each containing 10 male swiss webster albino mice; group A received standard dry pellet diet as control, group B received cholesterol and fat-enriched diets (CFED), group C and D received CFED and 150 and 300 mg/kgBW of kombucha drink from Sea grapes respectively for 4 weeks.. Sea grapes kombucha drink improved lipid profiles in the way of reducing total cholesterol, triglyceride, LDL, and increasing HDL levels compared to CFED and normal groups. The effect was more robust following the incrementing dose of the Sea grapes excluding total cholesterol. The lipase inhibitory activity of Sea grapes kombucha drink was similar to orlistat at a dose of 250 μg/mL, otherwise, orlistat was superior in the lower doses.. Sea grapes kombucha drink treatment also induced weight loss and increased level of liver SOD. Kombucha drink from C. racemosa has good potential as a functional beverage with anti-obese and lipid improving activity.

Topics: Animals; Beverages; Caulerpa; Cholesterol; Humans; Kombucha Tea; Lipase; Male; Mice; Obesity; Orlistat; Swine; Triglycerides; Vitis

Innovations in drug therapy for obesity have had a limited impact on the body mass index, prevalence of medical complications, quality of life, and work potential of a substantial majority of affected persons.. What are the milestones of the changes in the expert approach to the pharmacological management of obesity in the past century?. To determine the changes in the experts' approach to the management of obesity, as presented in a widely used textbook in the United States.. The primary sources were chapters describing the management of obesity in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. Secondary sources were publications retrieved from Medline that clarified technical issues related to the development, regulatory approval, and use of the drugs mentioned in the Cecil Textbook of Medicine.. Pharmacological interventions aimed at increasing caloric expenditures through thermogenesis were recommended from 1927 through 1943. Thyroid extracts were prescribed even in the absence of demonstrated hypothyroidism or decreased basal metabolic rate throughout this period. Dinitrophenol was mentioned in 1937, but was banned soon thereafter. Appetite suppression with amphetamine was considered useful from 1943 through 1988, after which the drug was replaced with other centrally acting molecules, such as fenfluramine in 1988, sibutramine in 2000, and rimonabant in 2008, which were in turn withdrawn because of major adverse effects. In the past decade, obesity has been treated with the appetite suppressants phentermine-topiramate, bupropion-naltrexone, lorcaserin, and liraglutide, and with orlistat, a drug promoting fat malabsorption. The change in weight produced by these drugs is generally modest and transient.. The pharmacological management of obesity has remained frustratingly inefficient. The reasons for the relative lack of success may reside in the ever-growing access to dense, palatable, and relatively inexpensive food, coupled with the decrease in energy expenditure created by a sedentary lifestyle.

Topics: Anti-Obesity Agents; Expert Testimony; Humans; Obesity; Orlistat; Quality of Life; United States

Obesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (-10.96 kcal/mol against PPARα and -10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (-14.88 kcal/mol against PPARα and -13.64 kcal/mol against PPARγ), and its aglycone, quercetin (-10.08 kcal/mol in PPARα and -9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment.

Topics: Anti-Obesity Agents; Humans; Ligands; Lipids; Metabolic Syndrome; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phytochemicals; PPAR alpha; PPAR gamma; Quercetin; Rutin

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

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil-water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.

Topics: Animals; Biological Products; Dietary Fats; Digestion; Linoleic Acid; Lipase; Obesity; Oleic Acid; Orlistat; Rats; Sesamum; Swine; Triglycerides

Obesity is characterized by visceral fat accumulation and various metabolic disturbances that cause metabolic syndrome and obesity-related cardiovascular diseases (ORCVDs). Hence, treatments targeting obesity should also prevent ORCVDs. Nonetheless, lifestyle modification therapy alone is still insufficient to reduce the risk of ORCVDs, although most cardiovascular guidelines still list it as the only treatment for obesity. Additionally, conventional anti-obesity drugs, such as orlistat, phentermine-topiramate, and naltrexone-bupropion, can reduce body weight but have not demonstrated a clear reduction in the risk of ORCVDs. To overcome this unmet clinical need, newer anti-obesity drugs must exhibit not only sufficient and long-lasting weight loss but also obvious cardiovascular benefits. Given recent clinical findings and evidences, in this context glucagon-like peptide-1 receptor agonist is currently available as a candidate that is clinically positioned as a first-line anti-obesity agent for the effective prevention of ORCVDs in people with obesity.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Glucagon-Like Peptide-1 Receptor; Humans; Liraglutide; Obesity; Orlistat

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

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspase 8; Caspase 9; Diet, High-Fat; Inflammation; NF-E2-Related Factor 2; Obesity; Orlistat; Oxidative Stress; Rats; RNA, Messenger; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Water

Topics: Animals; Diet, High-Fat; Diet, Western; Glucose Intolerance; Lipase; Liver; Mice; Mice, Inbred C57BL; Obesity; Orlistat; Phalaris; Seeds; Weight Gain

Obesity is a global pandemic and is cause of serious concern in all regions of the world. It is important to raise the attention of health care professionals in order to provide early treatment of patients with obesity. Obesity management, however, varies greatly amongst endocrinologists with respect to attitudes to diagnosis and treatment. Aim of this study was to identify practices and needs of Italian endocrinologists with respect to people with obesity.. In this study, all members of the Italian Association of Clinical Endocrinologists (AME) were invited to participate in a web-based survey concerning the management of obesity.. The response rate was 24.1% (542/2248). Nutritional and obesity problems were reported as major areas of interest by 29.4% of the participants. A large proportion of patients seeking an endocrine consultation for other reasons are affected by obesity, but one in five respondents addressed the issue in 25% or less of the cases, while one in three always dealt with the problem. Obesity was managed personally/within a dedicated team by 42.6% of participants, while the remainders referred the patient to a dietician/nutritionist or a 2nd level center for obesity therapy. Metformin was used in a median of 30% of the patients (Interquartile range: 10-50) and liraglutide in 10% of the cases (IQR 0-30), while orlistat (median 0%; IQR 0-10) and naltrexone/bupropion (median 0%; IQR 0-5) were seldom prescribed. Cost of therapy was considered as the major limitation to the use of anti-obesity drugs, affecting adherence to long-term treatment. According to 41.9% of respondents, psychological support should be offered to all patients with obesity. Finally, 56% of participants believe that the availability of new drugs will increase the number of patients candidate to drug therapy.. In conclusion, it is of primary importance to raise the awareness of endocrinologists towards the problem of obesity and increase their confidence in managing this pathological condition.

Topics: Anti-Obesity Agents; Endocrinologists; Humans; Metformin; Obesity; Orlistat

Global prevalence of obesity is increasing.. To study the effect of bee bread (BB) on serum renal function parameters, oxidative stress, inflammatory and B-cell associated protein X (Bax) in the kidneys of high fat diet (HFD) obese rats.. Thirty-six male Sprague Dawley rats were used. Control: received rat diet and water (1 mL/kg); HFD group: received HFD and water (1 mL/kg): bee bread (BB) preventive or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg); BB or orlistat treatment: received BB (0.5 g/kg) or orlistat (10 mg/kg).. HFD group had increased body weight, Body Mass Index, Lee Obesity Indices, kidney weights, malondialdehyde, inflammatory markers, Bax; decreased glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, total antioxidant activity, no differences (. BB modulated most of these parameters, as corroborated by histology.

Topics: Animals; Antioxidants; bcl-2-Associated X Protein; Diet, High-Fat; Down-Regulation; Inflammation; Kidney; Male; NF-kappa B; Obesity; Orlistat; Oxidative Stress; Propolis; Rats; Rats, Sprague-Dawley; Water

The rising prevalence of obesity and its associated comorbidities represent a growing public health issue; in particular, obesity is known to be a major risk factor for cardiovascular disease. Despite the evidence behind the efficacy of orlistat in achieving weight loss in patients with obesity, no study thus far has quantified its long-term effect on cardiovascular outcomes. The purpose of this study is to explore long-term cardiovascular outcomes after orlistat therapy.. A propensity-score matched cohort study was conducted on the nation-wide electronic primary and integrated secondary healthcare records of the Clinical Practice Research Datalink (CPRD). The 36 876 patients with obesity in the CPRD database who had completed a course of orlistat during follow-up were matched on a 1:1 basis with equal numbers of controls who had not taken orlistat. Patients were followed up for a median of 6 years for the occurrence of the primary composite endpoint of major adverse cardiovascular events (fatal or non-fatal myocardial infarction or ischaemic stroke), and a number of secondary endpoints including primary endpoint components individually, the occurrence of new-onset heart failure, coronary revascularization, new chronic kidney disease stage III+ (CKD3+), and all-cause mortality. During the median study follow-up of 6 years, the occurrence of major adverse cardiovascular events was lower in the orlistat cohort [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.66-0.83, P < 0.001]. Patients who took orlistat experienced lower rates of myocardial infarction (HR 0.77; 95% CI 0.66-0.88, P < 0.001) and ischaemic stroke (HR 0.68; 95% CI 0.56 to -0.84, P < 0.001) as well as new-onset heart failure (HR 0.79; 95% CI 0.67-0.94, P = 0.007). There was no differences in revascularization rates (HR 1.12; 95% CI 0.91-1.38, P = 0.27), but a lower rate of both CKD3+ development (HR 0.78; 95% CI 0.73-0.83, P < 0.001) and mortality (HR 0.39, 95% CI 0.36 to -0.41, P < 0.001) was observed.. In this nation-wide, propensity-score matched study, orlistat was associated with lower rates of overall major adverse cardiovascular events, new-onset heart failure, renal failure, and mortality. This study adds to current evidence on the known improvements in cardiovascular risk factor profiles of orlistat treatment by suggesting a potential role in primary prevention.

Topics: Brain Ischemia; Cardiovascular Diseases; Cohort Studies; Humans; Obesity; Orlistat; Stroke

Obesity is an important risk factor for severe acute pancreatitis. The necrosis of epididymal adipose tissue occurs in severe acute pancreatitis. Adipose tissue macrophages play an important role in metabolic related inflammation. Therefore, we explored the potential mechanisms between adipose tissue macrophages and obesity-related severe acute pancreatitis.. Severe acute pancreatitis mice model was induced by caerulein with lipopolysaccharide. The severity of severe acute pancreatitis was evaluated according to the morphological, general, and biochemical change. We assessed the injury of epididymal white adipose tissue, pancreas, and adipose tissue macrophages in obese mice and lean mice with severe acute pancreatitis. Outcomes of caerulein-induced severe acute pancreatitis were studied in lean and obese mice with or without lipase inhibitor orlistat.. Fat necrosis and pancreatic injury increased in the SAP groups. High levels of serum free fatty acid and triglyceride were increased significantly in the SAP group. The NLRP3-caspase1 inflammasome signal pathway in adipose tissue macrophages markedly enhanced in the SAP groups compared with control group. Free fatty acid can trigger macrophages inflammation through NLRP3-caspase1. Lipase inhibited by orlistat remarkably decreased in adipose tissue necrosis, and the levels of serum lipase, amylase, and pancreatic tissue damage decreased in the orlistat group compared with the SAP group. The NLRP3-caspase1 inflammasome pathway in adipose tissue macrophages markedly decreased in the orlistat groups compared with SAP group. The levels of serum free fatty acid and triglyceride were decreased significantly in the orlistat group.. Inflammation increases in adipose tissue macrophages of obese mice with severe acute pancreatitis. Free fatty acid generated via adipocyte lipolysis worsens inflammation in adipose tissue macrophages and the outcome of severe acute pancreatitis in obese mice through the NLRP3-caspase1 inflammasome pathway.

Topics: Acute Disease; Adipose Tissue; Animals; Caspase 1; Ceruletide; Fatty Acids, Nonesterified; Inflammasomes; Inflammation; Lipase; Macrophages; Mice; Necrosis; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity; Orlistat; Pancreatitis; Triglycerides

Topics: Animals; Biomarkers; Diet, High-Fat; Disease Models, Animal; Gastrointestinal Microbiome; Lactobacillus plantarum; Mice; Mice, Inbred C57BL; Obesity; Orlistat; Peroxisome Proliferator-Activated Receptors; Probiotics

Chronic diseases, such as obesity, cause great harm to human health. Conventional drugs have promising therapeutic effects but also cause significant side effects. Functional foods are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, screening for active ingredients in natural foods is difficult. In this study, a novel pancreatic lipase inhibitor screening strategy, guided by the drug molecule orlistat, was combined with experimental verification. Twenty compounds from natural foods were evaluated based on the characteristics of orlistat interaction with pancreatic lipase. The characteristics of 13 molecules were comparable to those of orlistat. The pancreatic lipase inhibition rates of curcumin and sinensetin were 82.42 ± 0.50% and 81.07 ± 2.05%, respectively, and their IC

Topics: Animals; Anti-Obesity Agents; Cholesterol; Drug Evaluation, Preclinical; Enzyme Inhibitors; Flavonoids; Functional Food; Lipase; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Molecular Dynamics Simulation; Obesity; Orlistat; Pancreas; Triglycerides; Weight Gain

Topics: Animals; Cyclic GMP; Diet, High-Fat; Hyperlipidemias; Inflammation; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Nucleotides, Cyclic; Obesity; Orlistat; Propolis; Rats; Rats, Sprague-Dawley; Signal Transduction; Vasodilation

Pancreatic lipase (PNLIP) is a digestive enzyme that is a potential drug target for the treatment of obesity. A better understanding of its regulation mechanisms would facilitate the development of new therapeutics. Recent studies indicate that intestinal lipolysis by PNLIP is reduced by Angiopoietin-like protein 4 (ANGPTL4), whose N-terminal domain (nANGPTL4) is a known inactivator of lipoprotein lipase (LPL) in blood circulation and adipocytes. To elucidate the mechanism of PNLIP inhibition by ANGPTL4, we developed a novel approach, using isothermal titration calorimetry (ITC). The obtained results were compared with those of well-described inhibitors of PNLIP - ε-polylysine (EPL), (-)-epigallocatechin-3-gallate (EGCG) and tetrahydrolipstatin. We demonstrate that ITC allows to investigate PNLIP inhibition mechanisms in complex substrate emulsions and that the ITC-based assay is highly sensitive - the lowest concentration for quantification of PNLIP is 1.5 pM. Combining ITC with surface plasmon resonance and fluorescence measurements, we present evidence that ANGPTL4 is a lipid-binding protein that influences PNLIP activity through interactions with components of substrate emulsions (bile salts, phospholipids and triglycerides), and this promotes the aggregation of triglyceride emulsions similarly to the PNLIP inhibitors EPL and EGCG. In the absence of substrate emulsion, unlike in the case of LPL, ANGPTL4 did not induce the inactivation of PNLIP. Our data also prove that due to various interactions with components of substrate systems, the effect of a PNLIP inhibitor depends on whether its effect is measured in a complex substrate emulsion or in a simple substrate system.

Topics: Angiopoietin-Like Protein 4; Anti-Obesity Agents; Calorimetry; Catechin; Drug Evaluation, Preclinical; Enzyme Assays; Humans; Lipase; Obesity; Orlistat; Polylysine; Recombinant Proteins

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Hesperidin; Hyperlipidemias; Inflammation; Insulin Resistance; Leptin; Molecular Docking Simulation; Molecular Dynamics Simulation; Obesity; Orlistat; Rats, Wistar

Steroidogenesis decline is reported to be one of the mechanisms associated with obesity-induced male factor subfertility/infertility.. We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline.. Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12 weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.. Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group).. Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.

Topics: Animals; Anti-Obesity Agents; Gene Expression Regulation; Gonadal Steroid Hormones; Infertility, Male; Male; Obesity; Orlistat; Random Allocation; Rats; Rats, Sprague-Dawley; Spermatogenesis; Up-Regulation

Obesity has been reported to induce oxidative stress, inflammation and apoptosis in the testis. The objective of this study was to determine the effects of the anti-obesity drug orlistat, on testicular oxidative stress, inflammation and apoptosis in high-fat diet (HFD)-fed rats. Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control (NC), high-fat diet (HFD), HFD plus orlistat (10 mg/kg body weight/day administered concurrently for 12 weeks) (HFD + Opr) and HFD plus orlistat (10 mg/kg body weight/day administered 6 weeks after induction of obesity) (HFD + Ot) groups. Antioxidant enzymes activities were significantly decreased, while mRNA levels of pro-apoptotic markers (p53, Bax/BCl-2, caspase-9, caspase-8 and caspase-3) were significantly increased in the testis of HFD group relative to NC group. Furthermore, the mRNA levels of pro-inflammatory markers (nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis factor alpha and interleukin (IL)-1β increased significantly, while anti-inflammatory marker (IL-10) decreased significantly in the testis of the HFD group relative to NC group. However, in both models of orlistat intervention (protective and treatment models) up-regulated antioxidant enzymes, down-regulated inflammation and apoptosis were observed in the testis of HFD-fed rats. Orlistat ameliorated testicular dysfunction by attenuating oxidative stress, inflammation and apoptosis in HFD-fed rats, suggesting its potential protective and therapeutic effects in the testis compromised by obesity.

Topics: Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Antioxidants; Apoptosis; Body Weight; Diet, High-Fat; Male; Obesity; Orlistat; Oxidative Stress; Rats, Sprague-Dawley; Testis

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague-Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.

Topics: Animals; Anti-Obesity Agents; Diet, High-Fat; Infertility, Male; Ion Transport; Lactates; Male; Obesity; Orlistat; Oxidative Stress; Rats; Rats, Sprague-Dawley; Testis

The purpose of this study was to develop an oral dosage form of orlistat for the treatment of obesity with reduced adverse effects, for example, fatty and oily stool that have been reported to be associated with the mechanism of action of orlistat. Based on the in vitro results obtained in this study, xanthan gum was selected as an oil-entrapping agent. Thus, the co-administration of mini-tablets containing orlistat and mini-tablets containing xanthan gum was proposed as the optimized dosage form for orlistat. The prepared mini-tablets showed an equivalent drug release profile with a similarity factor value, f

Topics: Animals; Delayed-Action Preparations; Obesity; Orlistat; Polysaccharides, Bacterial; Rats; Rats, Sprague-Dawley; Solubility; Tablets

Topics: Adenylate Kinase; Animals; Anti-Obesity Agents; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Down-Regulation; Humans; Lipid Metabolism; Liver; Male; Mesocricetus; Obesity; Orlistat; Phosphorylation; Plant Extracts; Rhodophyta; Signal Transduction; Uncoupling Protein 2; Up-Regulation; Water

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (

Topics: 3T3-L1 Cells; Activating Transcription Factor 3; Adipocytes, Brown; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Anti-Obesity Agents; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Body Temperature Regulation; Diet, High-Fat; Disease Models, Animal; Humans; Insulin Resistance; Lipogenesis; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Orlistat; Plant Extracts; Plants, Medicinal; Salvia miltiorrhiza

The role of proinflammatory cytokines in adiposity is well established. The anti-inflammatory and antihyperglycemia effects of Boswellia serrata (B. Serrata) gum have been demonstrated by many investigators. The present study aimed to investigate the anti-obesity potential of B. serrata extract.. The effects of B. serrata extract on lipase activity and acute food intake were investigated. The present study aimed to investigate the anti-obesity potential of B. serrata extract. The effects on lipase activity and acute food intake were investigated. Body weight changes, biochemical and histopathological markers were demonstrated in rats fed a high-fat diet.. Boswellia serrata extract inhibited alterations in pancreatic lipase activity, but orlistat was more efficacious. B. serrata and ephidrene, but not orlistat, significantly suppressed cumulative food intake in mice. In obese rats, B. serrata or orlistat significantly decreased weight gain and weight of visceral white adipose tissue. B. serrata-treated animals exhibited a significant reduction in serum glucose, TC, TG, LDL-C, FFA, IL-1β, TNF-α, insulin and leptin levels of obese rat groups while HDL-C and adiponectin levels were significantly increased by orlistat or B. serrata extract. Histopathological examination of the liver revealed that B. serrata was more effective than orlistat in alleviating steatosis and adipocyte hypertrophy shown in obese control rats.. Boswellia serrata is as effective as orlistat in preventing obesity, hyperlipidemia, steatosis and insulin resistance. These actions may be mediated by suppression of food intake and decrease levels of TNF-α, IL-1β and leptin resistance along with increasing adiponectin.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adiposity; Animals; Anti-Obesity Agents; Biomarkers; Body Weight; Boswellia; Cytokines; Diet, High-Fat; Eating; Hyperlipidemias; Insulin Resistance; Lipase; Male; Mice; Obesity; Orlistat; Plant Extracts; Polyphenols; Rats; Rats, Wistar; Resins, Plant

Orlistat is an intestinal lipase inhibitor drug that is recommended in obese patients along with a hypocaloric diet. Although the most frequent secondary effect is steatorrhea, fulminant liver failure has also been associated with this drug, which has required liver transplantation in 3 patients. We present the case of a 42-year-old obese male.

Topics: Adult; Anti-Obesity Agents; Fatty Liver; Humans; Liver Failure, Acute; Male; Massive Hepatic Necrosis; Obesity; Orlistat

To determine the efficacy of Corchorus olitorius (C. olitorius) leaf extract in the prevention of metabolic syndrome induced in rats by high-fat diet (HFD) and compare it with that of orlistat.. Phytochemical analysis was performed. Effect of orlistat and C. olitorius extract on lipase activity and acute food intake were investigated. Body weight, biochemical parameters and histopathological examination were demonstrated.. Corchorus olitorius extract inhibited the pancreatic lipase activity, but orlistat was more potent. Cumulative food intake has not changed by the tested agents. In obese rats, C. olitorius or orlistat significantly decreased weight gain and visceral white adipose tissue. They exhibited a significant reduction in serum glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, IL-1β, tumour necrosis factor-α (TNF-α), insulin and leptin levels of obese rat groups while high density lipoprotein cholesterol and adiponectin levels were significantly increased by them. Histopathological examination of the liver revealed that C. olitorius was more effective than orlistat in the alleviating of steatosis and adipocyte hypertrophy shown in obese control rats.. Corchorus olitorius is effective as orlistat in preventing obesity, hyperlipidaemia, steatosis and insulin resistance. These actions may be mediated by inhibiting of lipase activity, TNF-α, IL-1β and leptin resistance along with increasing of adiponectin.

Topics: Adiponectin; Animals; Anti-Obesity Agents; Corchorus; Cytokines; Diet, High-Fat; Hyperlipidemias; Insulin; Insulin Resistance; Leptin; Lipase; Male; Metabolic Syndrome; Obesity; Orlistat; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Weight Gain

Orlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat (VF) accumulation in Japanese individuals. Therefore, this study aimed to analyze the efficacy and safety of 52 weeks of orlistat administration in Japanese individuals.. Orlistat 60 mg was administered orally three times daily for 52 weeks to Japanese participants with excessive VF accumulation and without dyslipidemia, diabetes mellitus, and hypertension (metabolic diseases). Participants were also counseled to improve their diet and to maintain exercise habits. We defined excessive VF accumulation as a waist circumference (WC) of ≥ 85 cm for males and ≥ 90 cm for females, which corresponds to a VF area of 100 cm. VF, WC, and BW were significantly reduced at week 52 from baseline; the mean ± standard error rate of change was - 21.52% ± 1.89%, - 4.89% ± 0.45%, and - 5.36% ± 0.56%, respectively, and continued to reduce throughout the 52 weeks; these significantly reduced at whole term compared with baseline. Most adverse reactions were defecation-related symptoms such as oily spotting and flatus with discharge (flatus with small amounts of stool or oil) due to the pharmacologic effects of the lipase inhibitor. These symptoms were mostly mild, reversible, and recognizable by the participants; none were serious or severe. No participants discontinued by medical judgment about adverse reactions, and the drug could be administered continuously.. VF, WC, and BW were reduced from week 4 to week 52, indicating the effect of long-term orlistat administration. Moreover, it was well tolerated with an acceptable safety profile. Long-term administration of orlistat may be efficacious in reducing VF accumulation with safety when used in combination with diet and exercise.. This study is registered with the Japan Pharmaceutical Information Center (identifier: JapicCTI-184004).. Funding for this study was provided by Taisho Pharmaceutical Co., Ltd.

Topics: Adult; Anthropometry; Anti-Obesity Agents; Body Weight; Female; Humans; Intra-Abdominal Fat; Japan; Lactones; Longitudinal Studies; Male; Middle Aged; Obesity; Orlistat

Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid) hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media) and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.

Topics: Aluminum Compounds; Anti-Obesity Agents; Clay; Dietary Supplements; Digestion; Fatty Acids; Humans; Hydrolysis; Intestinal Absorption; Lipase; Lipids; Lipolysis; Magnesium Compounds; Nanoparticles; Obesity; Orlistat; Particle Size; Silicates; Surface Properties

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

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p = .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p < .05). Side effects were less with orlistat than metformin. This study demonstrated that orlistat is more effective in reducing weight and lipid profile than metformin. Besides, orlistat has mild side-effects and is better tolerated compared with metformin.

Topics: Adult; Anti-Obesity Agents; Cyproterone Acetate; Drug Combinations; Drug Therapy, Combination; Ethinyl Estradiol; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Young Adult

Arq zeera is a distillate product that prepared from four different herbs namely Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to determine the antiobesity effect of arq zeera and its main components thymol and cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of action. In current study, orlistat was used as positive controls. Male Wistar rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and orlistat for 28 days. During the course of treatment, body weight and food intake frequently observed and after end of treatments, liver weight, visceral fat pad weight, plasma lipid proflie, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity were studied on all treated obese rats. The histopathology of liver was also studied. After the treatments of arq zeera and its main components, body weight, food intake, liver weight, visceral fat pad weight and the level of lipid profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin, and leptin were found to be decreased and pancreatic lipase inhibition were increased. Arq zeera showed more potential antiobesity effect than orlistat. According to our present findings, arq zeera and its main components possessed potent antiobesity effect on high fat diet -induced obese rats and excreted anti-obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic, hypoleptinemic and pancreatic lipase inhibition action.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Benzaldehydes; Blood Glucose; Cymenes; Diet, High-Fat; Disease Models, Animal; Humans; India; Leptin; Lipase; Lipid Metabolism; Lipids; Liver; Male; Medicine, Unani; Obesity; Orlistat; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Thymol; Treatment Outcome

Polycystic ovary syndrome is one of the most common endocrinopathies in young women, and it affects 6% to 8% of women in reproductive age. Hyperandrogenism is the hallmark of polycystic ovary syndrome. The aim of the present study was to evaluate the effects of orlistat on weight loss and serum androgen levels among Iranian women with polycystic ovary syndrome.. The present study was carried out in the clinic of Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Thirty-two patients with polycystic ovary syndrome were randomly enrolled. We measured serum androgens (Testosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone and sex hormone-binding globulin) before and after 12 weeks of treatment with orlistat. We used the Rotterdam Criteria for all patients and transvaginal sonography was performed.. The mean age of patients was 27.75±6.22 and the mean body mass index was 32.69±0.94 kg/m2. Comparing with baseline, treatment with orlistat resulted in a significant reduction in weight, BMI, and waist circumference (p=0.001). We also found a remarkable reduction in total testosterone levels (p>0.001). Treatment improved the sex hormone-binding globulin plasma levels, but the improvement was not statistically significant. There was no reduction in other androgen levels.. This study showed a significant reduction of weight and total testosterone level - the most important androgen in polycystic ovary syndrome - after 12 weeks of treatment with orlistat. Therefore, it seems that a short course of orlistat can be useful in the management of patients with polycystic ovary syndrome.

Topics: Adult; Androgens; Anti-Obesity Agents; Body Mass Index; Female; Humans; Iran; Obesity; Orlistat; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Treatment Outcome; Waist Circumference; Young Adult

Chronic diseases are on the rise and are associated with weight gain. Multidisciplinary strategies are required for its control.. The design was descriptive, observational and retrospective. The objectives of this communication were to describe the demographic and clinical characteristics and adverse reactions of overweight and obese people who were consumers of orlistat, attended by a call center during the period 2009 to 2017; and to identify the healthcare professional most consulted by them. The information was obtained from an existing database of a program of attention to people with overweight or obesity, interested in using orlistat (prospects) or users (patients). The study was carried out in Mexico and lasted seven years. The variables studied were demographic, clinical and adverse reactions.. A total of 311,913 requests were collected from 126 607 subjects (104 711 prospects interested in consuming orlistat and 21 896 patients who already took it). The main activities were phone calls to the subject (35.9%). There were 104 711 requests: 82 810 (79.1%) prospects and 21 896 (20.9%) patients. 79.9% of all were female. The predominant age interval was 32 to 45 years. 43 adverse reactions (0.02%) were detected; the most common were abdominal pain (0.05%) and headache (0.03%).. The population most interested in weight control in this study was the female population (79.9%) and the age group from 32 to 45 years. The most consulted healthcare professional was the nutritionist. Only the body mass index (29.2 kilograms per square meter) of the subjects who developed 43 adverse reactions was obtained. There were 43 adverse reactions, the most common being abdominal pain and headache.. Las enfermedades crónicas van en ascenso y están asociadas al incremento ponderal. Se requieren estrategias multidisciplinarias para su control.. El diseño es descriptivo, observacional y retrospectivo. Los objetivos de esta comunicación son describir las características demográficas, clínicas y reacciones adversas de personas con sobrepeso y obesidad consumidores de orlistat, atendidos por un centro de atención telefónica durante el periodo 2009 a 2017; e identificar al profesional de la salud más consultado por ellos. La información se obtuvo desde una base de datos existente de un programa de atención a personas con sobrepeso u obesidad, interesadas en usar orlistat (prospectos) o usuarios (pacientes). El estudio se llevó a cabo en México y duró siete años. Las variables estudiadas fueron demográficas, clínicas y reacciones adversas.. Se reunieron 311 913 solicitudes de 126 607 sujetos (104 711 prospectos interesados en consumir orlistat y 21 896 pacientes que ya lo tomaban). Las principales actividades fueron llamadas al sujeto (35,9%). Hubo 104 711 solicitudes: 82 810 (79,1%) prospectos y 21 896 (20,9%) pacientes. El 79,9% fue de sexo femenino. El intervalo de edad predominante fue de 32 a 45 años. Se detectaron 43 reacciones adversas (0,02%); las más comunes fueron dolor abdominal (0,05%) y cefalea (0,03%).. La población más interesada en el control ponderal en este estudio es la femenina (79,9%) y el grupo etario de 32 a 45 años. El profesional más consultado fue el nutriólogo. Solo se obtuvo el índice de masa corporal (29,2 kilogramos por metro cuadrado) de los sujetos que desarrollaron 43 reacciones adversas, las más comunes fueron dolor abdominal y cefalea.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Anti-Obesity Agents; Call Centers; Female; Headache; Health Personnel; Humans; Male; Mexico; Middle Aged; Obesity; Orlistat; Overweight; Retrospective Studies; Young Adult

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

The incidence of obesity is rising at an alarming rate throughout the world and is becoming a major public health concern with incalculable social and economic costs.

Topics: Adiposity; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Blood Glucose; Diet, High-Fat; Disease Models, Animal; DNA-Binding Proteins; Gene Expression Regulation; Glucose Tolerance Test; Insulin; Lactones; Male; Mice; Mice, Inbred ICR; Obesity; Organ Size; Orlistat; Plant Extracts; Rhodophyta; Signal Transduction; Transcription Factors; Uncoupling Protein 1; Weight Gain

This experimental study was carried out to evaluate the efficacy of orlistat (a pancreatic lipase inhibitor) therapy over lifestyle change on weight reduction and ovulation in overweight and obese subfertile women. It was carried out in Department of Gynecology and Obstetrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh from August 2015 to January 2016. Subfertile obese and overweight female patients attending the study centre during study period was considered as study population. Subfertile women with normozoospermic husband with BMI (25-40) Kg/M2, age (18-35) years with no history of taking medication or dietary modification for weight loss currently or for the preceding 3 months were included in this study but subfertile patients having laparoscopic ovarian drilling and metformin and those with structural abnormalities in reproductive tract and known hormonal and medical disorder were excluded from this study. Detailed history taking, physical examination including weight, Body Mass Index (BMI) and baseline relevant investigations were done. Transvaginal sonography (TVS) on day 12 and day 14 of menstrual cycle was done for evaluation of ovulatory status of the patients. Counseling was done about life style change by diet of low glycemic index and moderate exercise. Following written informed consent, 120 patients were enrolled into either of the two groups. Group I received capsule Orlistat 120 mg twice daily for 3 months period. Group II was counseled for life style modification only. Post treatment weight measurement and TVS on day 12 and 14 were done after completion of intervention. Then pre and post-treatment parameters were assessed between two groups. Mean age was (27.31±4.58) years in Group I and (26.20±4.71) years in Group II. Majority patients, (78.3%) in Group I and (76.7%) in Group II had oligomenorrhoea. Hirsuitism was observed in (25%) in Group I and (43.3%) in Group II. Mean weight (kg) at booking was (72.26±7.81) in Group I and (67.10±5.93) in Group II; after 3 months (67.77±7.82) and (63.55±6.07). Reduction of weight (%): (6.52±2.28) in Group I and (5.33±2.14) in Group II which was significantly higher in Group I than that of Group II in (25.0-29.9) BMI. Ovulation assessed by TVS at booking and after 3 months in Group I: 13(21.7%) and 37 (61.7%) and in Group II: 14 (23.3%) and 27 (45.0%). Ovulation was higher in Group I than that of Group II, but the difference was not statistically significant. Majority of t

Topics: Adult; Bangladesh; Diet, Reducing; Female; Humans; Infertility, Female; Lactones; Lipase; Obesity; Orlistat; Overweight; Young Adult

The increasing rate of obesity in the past years has become a worldwide concern and it causes many diseases. Even though, Orlistat, a synthetic anti-obesity drug approved by FDA, it causes severe side effects. DATS, a natural product from garlic have gained attention in many biological activities. The aim of the study is to determine the impact of Dially trisulpide (DATS) and its combination with Orlistat therapy on obese animals. 30 male Wistar rats (150-180g) were assigned into 5 groups (n=6). Group 1 rats received normal diet and Group 2 fed with high fat diet (HFD) for 14 weeks. Group 3-5 animals fed with HFD for 8 weeks, after that respective drugs were given simultaneously along with HFD for 6 weeks; Group 3: HFD+Orlistat; Group 4: HFD+DATS; Group 5: HFD+Orlistat+DATS. Before and after drug treatment, body weight was measured and blood was collected for assessment of lipid and liver function profiles. After end of the treatment 14 weeks, liver and adipose tissues were collected for antioxidants determination and histological observations. The significantly (p<0.05) increased body weight, serum glucose, total cholesterol, triglycerides, LDL-cholesterol were observed while significantly (p<0.05) decreased HDL-cholesterol and liver function parameters in HFD induced rats when compared to control group. The significantly (p<0.05) decreased activities of SOD, CAT, GPx and GSH levels were observed while significantly (p<0.05) increased LPO in both the tissues of HFD treated group when compared to control. Histopathological changes were observed in both the liver and adipose tissue of HFD treated group. The DATS and its combination with orlistat supplementation restored all the parameters significantly (p<0.05) especially liver function parameters and also retrieved histopathological changes when compared to orlistat alone. DATS and its combination with Orlistat had great effect than Orlistat alone.

Topics: Adipose Tissue; Allyl Compounds; Animals; Anti-Obesity Agents; Antioxidants; Body Mass Index; Body Weight; Cholesterol; Diet, High-Fat; Garlic; Lactones; Liver; Male; Obesity; Orlistat; Phytotherapy; Plant Extracts; Protective Agents; Rats; Rats, Wistar; Sulfides; Triglycerides; Weight Gain

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

Topics: Anti-Obesity Agents; Body Weight; Humans; Lactones; Lipids; Meta-Analysis as Topic; Obesity; Orlistat; Randomized Controlled Trials as Topic

Obesity is a serious, chronic, relapsing disease of energy regulation, with strong genetic and early-life environmental determinants. Pharmacotherapy can be a useful adjunct to lifestyle intervention in effecting and maintaining clinically meaningful weight loss.. The aim of this article is to discuss the role of pharmacotherapy in obesity management. The efficacy, side effects and contraindications of available weight-loss medications are reviewed.. Long-term pharmacotherapy options, which can be effective in providing moderate weight loss, are available to treat obesity. Pharma-cotherapy should be considered an adjunct to lifestyle intervention in those with a body mass index (BMI) >30 kg/m30 kg/m2, or in those with a BMI of 27-30 kg/m2 and obesity-related complications. Safety and efficacy should be monitored closely on commencement, and the medication should be discontinued if there are safety or tolerability issues, or if.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Drug Therapy; Drug Therapy, Combination; Fructose; Humans; Incretins; Lactones; Liraglutide; Obesity; Orlistat; Phentermine; Topiramate

Citrus fruit and olive leaves are a source of bioactive compounds such as biophenols which have been shown to ameliorate obesity-related conditions through their anti-hyperlipidemic and anti-inflammatory effect, and by regulating lipoproteins and cholesterol body levels. Citrolive™ is a commercial extract which is obtained from the combination of both citrus fruit and olive leaf extracts; hence, it is hypothesised that Citrolive™ may moderate metabolic disorders that are related to obesity and their complications. Initially, an in vitro study of the inhibition of pancreatic lipase activity was made, however, no effect was found. Both preliminary and long-term evaluations of Citrolive™ on lipid metabolism were conducted in an animal model using Wistar rats. In the preliminary in vivo screening, Citrolive™ was tested on postprandial plasma triglyceride level after the administration of an oil emulsion, and a significant reduction in postprandial triacylglycerol (TAG) levels was observed. In the long-term study, Citrolive™ was administered for 60 days on Wistar rats that were fed a high-fat diet. During the study, several associated lipid metabolism indicators were analysed in blood and faeces. At the end of the experiment, the livers were removed and weighed for group comparison. Citrolive™ treatment significantly reduced the liver-to-body-weight ratio, as supported by reduced plasma transaminases compared with control, but insignificantly reduced plasma low density lipoprotein (LDL) and postprandial TAG plasma levels. In addition, faecal analysis showed that the treatment significantly increased total cholesterol excretion. On the other hand, no effect was found on faecal TAG and pancreatic lipase in vitro. In conclusion, treatment ameliorates liver inflammation symptoms that are worsened by the effects of high fat diet.

Topics: Animals; Anti-Obesity Agents; Biomarkers; Cholesterol; Citrus; Diet, High-Fat; Disease Models, Animal; Feces; Fruit; Lactones; Lipase; Lipid Metabolism; Lipids; Lipoproteins, LDL; Male; Obesity; Olea; Orlistat; Plant Extracts; Plant Leaves; Postprandial Period; Rats, Wistar; Time Factors; Triglycerides

Two patients developed kidney failure due to oxalate deposition in the kidney while taking orlistat. Cessation of orlistat was followed by partial recovery of kidney function. The mechanism by which orlistat causes hyperoxaluria and the management of orlistat-induced oxalate nephropathy is reviewed. We suggest that all patients taking orlistat are at risk of this condition, which may develop insidiously and is easily overlooked. Monitoring of kidney function of patients taking orlistat is warranted.

Topics: Aged; Anti-Obesity Agents; Calcium Oxalate; Female; Humans; Hyperoxaluria; Kidney Tubular Necrosis, Acute; Lactones; Male; Microscopy; Obesity; Orlistat; Renal Insufficiency, Chronic

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

Topics: Anti-Obesity Agents; Body Mass Index; Family Practice; Humans; Lactones; Liraglutide; Obesity; Orlistat; Practice Guidelines as Topic; Practice Patterns, Physicians'

Topics: Anti-Obesity Agents; Body Mass Index; Family Practice; Humans; Lactones; Liraglutide; Male; Metformin; Obesity; Orlistat; Practice Guidelines as Topic; Practice Patterns, Physicians'

Pancreatic lipase (PL) is a primary lipase critical for triacylglyceride digestion in humans and is considered as a promising target for the treatment of obesity. Although the current synthetic drugs available for treating obesity have been demonstrated to be effective in inhibiting PL, their prolonged usage results in severe side effects. Based on this argument, in this study, we evaluated the structural and energetic features linked to molecular recognition between two well-known PL inhibitors, orlistat (ORL, synthetic inhibitor) and (-)-epigallocatechin gallate (EGCG, natural inhibitor) and PL through molecular dynamics simulations and free energy calculations of ORL and EGCG at the PL binding site when it is isolated (PL) from the heterodimer complex, forming the heterodimer complex with colipase (PLCL) and lacking structural calcium. Our study showed that the binding free energy of ORL and EGCG to the target correlates with their experimental affinity tendency. The presence of the heterodimer PLCL state, the presence of structural calcium and the type of inhibitor resulted in differences in structural stability and in the map of protein-ligand and protein-protein interactions. Overall, our results suggest that the heterodimer complex and structural calcium are linked to the binding properties of PL.

Topics: Catechin; Enzyme Inhibitors; Humans; Kinetics; Lactones; Ligands; Lipase; Molecular Dynamics Simulation; Obesity; Orlistat; Pancreas

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

To highlight the prevalence and impact of obesity in the United States and provide nurse practitioners (NPs) with an overview of pharmacotherapy options for treatment of overweight and obese individuals.. A comprehensive review of the literature was conducted using multiple databases, including PubMed, MEDLINE, and Ovid. Keywords used to obtain relevant articles included obesity and drug, or orlistat, topiramate/phentermine, lorcaserin, bupropion/naltrexone, and liraglutide.. Obesity is a prevalent disease with more than two thirds of Americans being considered overweight and one third being obese. Obesity places patients at an increased risk for many comorbidities that impact patient health as well as public health. There are currently five approved medications for the chronic management of obesity, two of which were approved in 2014. These pharmacological therapies are options to aid weight loss in patients that are obese or those who are overweight with additional risk factors.. NPs can assist patients struggling with their weight. With new pharmacotherapy options, there is an opportunity to add to diet and exercise in order to achieve increased weight loss. A decrease in obesity would potentially alleviate the burden on the healthcare system, both socially and economically, and improve patient quality of life.

Topics: Benzazepines; Bupropion; Disease Management; Fructose; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; United States

The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.

Topics: Adiposity; Animals; Anti-Obesity Agents; Biomarkers; Diet, High-Fat; Disease Models, Animal; Feces; Lactones; Male; Metabolomics; Morinda; Obesity; Orlistat; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Proton Magnetic Resonance Spectroscopy; Rats, Sprague-Dawley; Time Factors; Weight Gain

Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome.

Topics: Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Anti-Obesity Agents; Body Fat Distribution; Data Mining; Gene Expression Regulation; Gene Regulatory Networks; Humans; Insulin; Lactones; Leptin; Metabolic Networks and Pathways; Obesity; Orlistat; Protein Binding; Protein Interaction Maps; Proteins; Proteome; Risk Factors

This study aimed to evaluate the anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin (BA) in high-fat diet-induced obese male C57BL/6 mice. BA at doses of 50, 100, and 200 mg/kg was supplemented in the daily food of obese C57BL/6 mice during an 8-week experiment. Our findings indicate that consumption of BA at high doses reduced body weight by 19.4%, whereas both low and middle doses did not affect the body weight. Furthermore, BA supplementation at high dose could effectively decrease serum glucose, attenuate epididymal adipocytes, improve lipid profiles, and significantly down-regulate expression levels of TNFα, IL-6 PPARγ, and FAS genes. Therefour, BA might alter bodyweight by suppressing fatty acid synthesis and alleviating inflammation.

Topics: Animals; Anthocyanins; Blueberry Plants; Body Weight; Dietary Fats; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids; Gene Expression Regulation; Inflammation; Lactones; Male; Mice; Mice, Inbred C57BL; Obesity; Orlistat; Random Allocation

Orlistat is currently the only prescribed form of pharmacological management for obesity and functions by reducing the amount of fat absorbed from food eaten. Although frequently prescribed, there is marked variability in outcomes. A total of 10 participants' experiences of gaining weight after taking orlistat were analysed using thematic analysis. Participants attributed their failed weight loss to mechanisms of the medication, emphasised a medical model of obesity with barriers to their weight loss and other weight-loss methods which had also failed. Overall, their weight gain was considered an inevitable part of their self-identity, reflecting their self-fulfilling prophecy of being a perpetual dieter.

Topics: Adult; Aged; Anti-Obesity Agents; Diet; Female; Follow-Up Studies; Humans; Interviews as Topic; Lactones; Male; Medication Adherence; Middle Aged; Obesity; Orlistat; Qualitative Research; Self Concept; Treatment Failure; Weight Gain

Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials.. We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that "all adverse events were recorded." For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs.. In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles.

Topics: Anti-Obesity Agents; Bibliometrics; Clinical Protocols; Humans; Lactones; Obesity; Orlistat; Periodicals as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

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

A new benzylated and prenylated flavonone, cudracuspiflavanone A (17) were isolated from the roots of Cudrania tricuspidata (Moraceae), together with two chromones (1-2) and fourteen flavonoids (3-16). The structures of isolated compounds were determined on the basis of spectroscopic analysis. The absolute configuration was also defined by CD analysis. Among the isolated compounds, compounds 14 and 15 inhibited pancreatic lipase activity with an IC50 value of 9.0 and 6.5 μM, respectively.

Topics: Biological Products; Flavonoids; Lipase; Molecular Structure; Moraceae; Obesity; Pancreas; Plant Extracts

Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients.

Topics: 3T3-L1 Cells; Adipocytes; Adipokines; Animals; Cell Line, Tumor; Cell Proliferation; Diet; Diet, High-Fat; Disease Progression; Female; Humans; Lactones; Leptin; Male; Melanoma; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Obesity; Orlistat; Resistin; Skin Neoplasms

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

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

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

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

HT048 is a combination composed of Crataegus pinnatifida leaf and Citrus unshiu peel extracts. This study aimed to investigate potential anti-obesity effect of the combination. The 3T3-L1 adipocytes were treated with different doses of HT048 and triglyceride accumulation, glycerol release and adipogenesis-related genes were analyzed. For in vivo study, male Sprague Dawley rats were divided according to experimental diets: the chow diet group, the high-fat diet (HFD) group, the HFD supplemented with orlistat group, the HFD supplemented with HT048 group (0.2% or 0.4%) for 12 weeks. We measured the body weight, serum lipid levels and the expression of genes involved lipid metabolism. HT048 treatment dose-dependently suppressed adipocyte differentiation and stimulated glycerol release. The expressions of PPARγ and C/EBPα mRNA were decreased by HT048 treatment in adipocytes. HT048 supplementation significantly reduced the body and fat weights in vivo. Serum lipid levels were significantly lower in the HT048 supplemented groups than those of the HFD group. Expression of the hepatic lipogenesis-related genes were decreased and expression of the β-oxidation-related genes were increased in rats fed HT048 compared to that of animals fed HFD. These results suggest that HT048 has a potential benefit in preventing obesity through the inhibition of lipogenesis and adipogenesis.

Topics: 3T3-L1 Cells; Adipogenesis; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Citrus; Crataegus; Diet, High-Fat; Gene Expression Regulation; Glycerol; Lactones; Lipid Metabolism; Lipogenesis; Male; Mice; Obesity; Orlistat; Plant Extracts; PPAR gamma; Rats; Rats, Sprague-Dawley; Signal Transduction; Triglycerides

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

Currently, there is no therapy for severe acute pancreatitis (AP) except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor γ agonist rosiglitazone, and the chemokine receptor 2 antagonists attenuate the severity of AP in rodents if administered before or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis.. Male C57BL6 mice with diet-induced obesity received 2 injections of mrIL-12 (150 ng per mouse) and mrIL-18 (750 ng per mouse) intraperitoneally at 24-hour intervals. The mice were injected 2, 24, and 48 hours after the second injection of IL-12 + IL-18 with orlistat (2 mg per mouse), rosiglitazone (0.4 mg per mouse), RS102895 (0.3 mg per mouse), or vehicle (20 μL of DMSO and 80 μL of canola oil) and euthanized after 72 hours.. Orlistat decreased intra-abdominal fat necrosis compared with vehicle (P < 0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis.. Drugs previously shown to improve the severity of AP when given before or at the time of induction of pancreatitis failed to do so when administered therapeutically in the IL-12 + IL-18 model.

Topics: Acute Disease; Animals; Anti-Obesity Agents; Benzoxazines; Interleukin-12; Interleukin-18; Lactones; Male; Mice, Inbred C57BL; Obesity; Orlistat; Pancreatitis; Piperidines; Receptors, CCR2; Rosiglitazone; Severity of Illness Index; Thiazolidinediones; Treatment Failure; Vasodilator Agents

This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG) on fat accumulation and dyslipidemia in high fat diet- (HFD-) induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days+AqE-TFG (0.5 and 1.0 g/kg) or orlistat (10 mg/kg) from day 8 to 28), respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI), white adipose tissue (WAT) weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and lactate dehydrogenase (LDH) levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme (glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS) and glucose-6-phosphate dehydrogenase (G6PD)) activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.

Topics: Adipose Tissue, White; Amino Acids; Animals; Anthropometry; Antioxidants; Body Mass Index; Body Weight; Diet, High-Fat; Disease Models, Animal; Dyslipidemias; Female; Homeostasis; Lactones; Obesity; Orlistat; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Seeds; Trigonella; Weight Gain

This clinical practice guideline for treatment of DSM-5 feeding and eating disorders was conducted as part of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clinical Practice Guidelines (CPG) Project 2013-2014.. The CPG was developed in accordance with best practice according to the National Health and Medical Research Council of Australia. Literature of evidence for treatments of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified and unspecified eating disorders and avoidant restrictive food intake disorder (ARFID) was sourced from the previous RANZCP CPG reviews (dated to 2009) and updated with a systematic review (dated 2008-2013). A multidisciplinary working group wrote the draft CPG, which then underwent expert, community and stakeholder consultation, during which process additional evidence was identified.. In AN the CPG recommends treatment as an outpatient or day patient in most instances (i.e. in the least restrictive environment), with hospital admission for those at risk of medical and/or psychological compromise. A multi-axial and collaborative approach is recommended, including consideration of nutritional, medical and psychological aspects, the use of family based therapies in younger people and specialist therapist-led manualised based psychological therapies in all age groups and that include longer-term follow-up. A harm minimisation approach is recommended in chronic AN. In BN and BED the CPG recommends an individual psychological therapy for which the best evidence is for therapist-led cognitive behavioural therapy (CBT). There is also a role for CBT adapted for internet delivery, or CBT in a non-specialist guided self-help form. Medications that may be helpful either as an adjunctive or alternative treatment option include an antidepressant, topiramate, or orlistat (the last for people with comorbid obesity). No specific treatment is recommended for ARFID as there are no trials to guide practice.. Specific evidence based psychological and pharmacological treatments are recommended for most eating disorders but more trials are needed for specific therapies in AN, and research is urgently needed for all aspects of ARFID assessment and management.. Associate Professor Susan Byrne, Dr Angelica Claudino, Dr Anthea Fursland, Associate Professor Jennifer Gaudiani, Dr Susan Hart, Ms Gabriella Heruc, Associate Professor Michael Kohn, Dr Rick Kausman, Dr Sarah Maguire, Ms Peta Marks, Professor Janet Treasure and Mr Andrew Wallis.

Topics: Anti-Obesity Agents; Antidepressive Agents; Australia; Chronic Disease; Cognitive Behavioral Therapy; Feeding and Eating Disorders; Fructose; Harm Reduction; Humans; Lactones; New Zealand; Obesity; Orlistat; Psychiatry; Societies, Medical; Topiramate

Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction.

Topics: Anti-Obesity Agents; Female; Humans; Lactones; Liver Failure, Acute; Middle Aged; Obesity; Orlistat

To measure the association between orlistat and acute liver injury.. Self controlled case series study.. Population based primary care setting, United Kingdom.. 94,695 patients receiving orlistat and registered in the UK Clinical Practice Research Datalink and linked with Hospital Episode Statistics data between 1999 and 2011.. Relative incidence of acute liver injury comparing periods when patients were receiving orlistat with periods of non-usage.. Among 94,695 patients who received orlistat, 988 cases of acute liver injury were identified, with 335 confirmed as definite cases and 653 as probable cases. For all cases an increased incidence of liver injury was detected during the 90 day period before orlistat was first started, with an incidence rate ratio of 1.50 (95% confidence interval 1.10 to 2.06). The incidence remained raised during the first 30 days of treatment (2.21, 1.43 to 3.42), before returning to baseline levels with prolonged treatment. When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of liver injury was not increased (1.02, 0.67 to 1.56). An analysis restricted to definite cases showed no evidence of an increased risk of liver injury during treatment.. The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug.

Topics: Adult; Anti-Obesity Agents; Case-Control Studies; Causality; Chemical and Drug Induced Liver Injury; Databases, Factual; Female; Humans; Incidence; Lactones; Male; Middle Aged; Obesity; Orlistat; Time Factors; United Kingdom

Cutaneous leukocytoclastic vasculitis (LCV), also known as small-vessel vasculitis, is a process thought to be related to the presence of circulating immune complexes. Leukocytoclastic vasculitis is thought to be idiopathic in up to 50% of cases, but other common causes and associated disorders include certain medications, most frequently antibiotics; infections; collagen-vascular disease; paraproteinemias; and rarely neoplasia. We report a patient with cutaneous LCV induced by orlistat, a pancreatic lipase inhibitor that works as a weight-loss agent by decreasing the absorption of dietary fat.

Topics: Anti-Obesity Agents; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Skin Diseases, Vesiculobullous; Vasculitis, Leukocytoclastic, Cutaneous

To examine the risk of colorectal cancer after orlistat initiation in the UK population.. Retrospective matched cohort study.. Data from the UK Clinical Practice Research Datalink from September 1998 to December 2008.. 33,625 adults aged 18 years or over who started treatment with orlistat; each orlistat initiator was matched to up to five non-initiators (n=160,347) on age, sex, body mass index, and calendar time.. Associations between orlistat initiation and the risk of colorectal cancer, assessed by calculating hazard ratios with propensity score adjusted Cox proportional hazard models.. Of 193,972 patients with a median age of 47 (interquartile range 37-57) years, 77% were women and approximately 90% were obese (body mass index ≥ 30). Orlistat initiators were more likely to have a previous history of diabetes or hypertension and to receive prescriptions for anti-diabetes drugs, statins, and aspirin compared with non-initiators. In the intention to treat analysis, 57 colorectal cancer events were identified among orlistat initiators and 246 among non-initiators, with median follow-up times of 2.96 and 2.86 years, respectively. The calculated incidence rate of colorectal cancer per 100,000 person years was 53 (95% confidence interval 41 to 69) for orlistat initiators and 50 (44 to 57) for non-initiators. Orlistat initiation was not associated with a higher risk of colorectal cancer (adjusted hazard ratio 1.11, 95% confidence interval 0.84 to 1.47). Findings were robust in the as treated analyses and in patients who were aged 50 years or over, were morbidly obese, or had a history of diabetes.. This study found no evidence of an increased risk of colorectal cancer after the initiation of orlistat. It is limited by the relatively short follow-up time, and the possibility of adverse effects of long term orlistat use on risk of colorectal cancer cannot be excluded.

Topics: Adult; Anti-Obesity Agents; Colorectal Neoplasms; Epidemiologic Methods; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat

Obesity is an emerging risk factor for chronic kidney disease (CKD) in the developed world. Orlistat, an intestinal lipase inhibitor, used in the treatment of obesity is available as an over-the-counter medication across the European union and in many countries worldwide. It is associated with acute kidney injury (AKI). We present three adults, followed up from 1 to 6 years, who developed de novo or worsening renal impairment while on orlistat. Stopping the drug halted progression, but did not reverse the degree of renal impairment at presentation.

Topics: Acute Kidney Injury; Aged; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Disease Progression; Essential Hypertension; Female; Humans; Hypertension; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Prognosis; Risk Factors

Topics: Adult; Guideline Adherence; Humans; Lactones; Medical Audit; Obesity; Orlistat; Practice Guidelines as Topic; Practice Patterns, Physicians'; State Medicine; Surveys and Questionnaires; United Kingdom

Obesity is a disease involving body weight gain. Several synthetic drugs of better efficacy are being introduced in the modern system of medicine. Orlistat is a pharmacological agent promoting weight loss in obese subjects via inhibiting of gastric and pancreatic lipase. Ginger (Zingiber officinale Roscoe, Zingiberacae) is one of the most commonly used spices around the world; it has long been used in traditional medicine as a cure for some diseases.. To evaluate the effect of ginger and orlistat on rats fed high fat diet.. Forty male Albino rats were either not treated (control), or fed high fat diet, or fed high fat diet with dietary orlistat supplementation (200 mg/kg diet), or fed high fat diet supplemented with 5% ginger powder. After four weeks of treatment, final body weight and food intake were determined. Blood samples were collected, lipid parameters, total bilirubin, pancreatic lipase were determined. Liver peroxisomes were isolated from rat livers and peroxisomal catalase activity was determined.. Treatment with both ginger and orlistat had significant effect in reducing body weight, besides, supplementing diet with orlistat increase food intake. Both ginger and orlistat had the ability to reduce lipid profile, ginger had great effect in increasing HDL-cholesterol than orlistat. When compared to the control group, ginger treatment did not alter either total bilirubin or pancreatic lipase activity while orlistat clearly reduced their concentration. Orlistat supplementation induced a significant reduction in peroxisomal catalase level, while ginger has been reported to interfere with enzyme activity increasing its level.. Ginger has a great ability to reduce body weight without inhibiting pancreatic lipase level, or affecting bilirubin concentration, with positive effect on increasing peroxisomal catalase level and HDL-cholesterol.

Topics: Animals; Anti-Obesity Agents; Bilirubin; Catalase; Lactones; Lipase; Lipids; Liver; Male; Obesity; Orlistat; Pancreas; Peroxisomes; Rats; Rats, Wistar; Weight Gain; Zingiber officinale

Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu people in Japan, but its chemical constituents are not much studied. Pancreatic lipase inhibitors are a promising tool for the treatment of obesity. We searched for natural lipase inhibitors from F. kamtschatica and two new compounds were isolated along with the known flavonoid glycoside. The structure elucidation of new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-L-threonic acid and 3-O-caffeoyl-4-O-galloyl-L-threonic acid, which can be recognized as a pancreatic lipase's substrate-like structure. The isolated compounds all showed an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3-O-caffeoyl-4-O-galloyl-L-threonic acid, possessed the most potent activity with IC(50) value showing an order lower value compared to others. The substrate-like structure of the new compounds seemed to be important for their activity.

Topics: Animals; Butyrates; Enzyme Inhibitors; Filipendula; Glycosides; Lipase; Obesity; Pancreas; Plant Extracts; Swine

A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

Topics: Animals; Benzimidazoles; Diacylglycerol O-Acyltransferase; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors; Hep G2 Cells; Humans; Mice; Mice, Obese; Microsomes, Liver; Molecular Structure; Obesity; Rats; Structure-Activity Relationship; Triglycerides

This study evaluated the anti-obesity effects of HT048, a combination of C. pinnatifida fruit and C. unshiu peel extracts, in high-fat diet (HFD)-induced obese rats. 4-Week-old male Sprague Dawley (SD) rats were divided into normal and high fat diet (HFD) groups. The HFD groups were further divided into five groups treated with distilled water, orlistat (40 mg/kg, twice daily, p.o) and HT048 (30, 100 and 300 mg/kg, twice daily, p.o.) for 12 weeks. Orlistat, an anti-obesity drug, was used as positive control in the HFD-induced obese rats. We measured the food intake, body weight, epididymal adipose tissue and liver weights, and serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) levels. The body weight and epididymal adipose tissue and liver weights of the HT048 100 and 300 mg/kg treated groups were significantly lower than that of the HFD control group. Also, serum TC, TG, ALT, and AST levels in the HT048 100 and 300 mg/kg treated groups were significantly decreased. Moreover, the orlistat treated group showed significantly reduced body weight and improved serum lipoprotein, compared with the HFD control group. These results show that HT048 supplements improved obesity-related body weight and serum lipoprotein parameters in a HFD-induced obese rat model.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Cholesterol; Crataegus; Diet, High-Fat; Dietary Fats; Drug Synergism; Fruit; Lactones; Male; Obesity; Orlistat; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Triglycerides

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

There has been a steady increase in the epidemiology of obesity over the last 30 years with developed countries leading the way. Oxidative stress was believed to be the principle contributor to the development of cardiovascular disorders that linked with obesity.. To evaluate the enhancement of antioxidant defense mechanism by Pitavastatin (PTV) and Rosuvastatin (RSV) on obesity-induced oxidative stress in Wistar rats.. Fifty Wistar albino rats were divided into five groups. High fat diet (HFD, 20 g/day/rat) pellets were given for 28 days to produce obesity-induced oxidative stress in Wistar rats. Oral administration of HFD along with PTV, RSV and Orlistat [(HFD for 28 days + from 8th day PTV (1 mg/kg), RSV (5 mg/kg) and Orlistat (10 mg/kg) to 28th day] were given respectively.. Both PTV and RSV produced significant (p < 0.01) reduction in serum apolipoprotein-B (Apo-B), total cholesterol (TC), triglycerides (TGs), cardiac-lipid peroxides (TBARS) levels and elevation in serum high density lipoprotein (HDL-C), cardiac antioxidant enzymes [glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catase (CAT)] levels.. Results were comparable with Orlistat, a standard antiobesity drug and present initial evidence that Pitavastatin and Rosuvastatin are useful for the treatment of obesity by enhancing the antioxidant defense mechanism. However, the effects of PTV were more prominent than RSV. The present findings of Pitavastatin and Rosuvastatin raise the possibility of a new application as an antiobesity therapeutic modality.

Topics: Administration, Oral; Animals; Anti-Obesity Agents; Antioxidants; Apolipoproteins B; Cholesterol, HDL; Disease Models, Animal; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Lipid Peroxides; Myocardium; Obesity; Orlistat; Oxidative Stress; Pyrimidines; Quinolines; Rats; Rats, Wistar; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome; Triglycerides

Topics: Adenine; Adult; Anti-HIV Agents; Anti-Obesity Agents; Deoxycytidine; Drug Combinations; Drug Interactions; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV; HIV Seropositivity; Humans; Lactones; Male; Nonprescription Drugs; Obesity; Organophosphonates; Orlistat; Oxazines; Reverse Transcriptase Inhibitors; RNA, Viral; Viral Load

Topics: Anti-Obesity Agents; Canada; Chemical and Drug Induced Liver Injury; Databases, Factual; France; Humans; Kidney Diseases; Lactones; Obesity; Orlistat; Oxalates

A high-fat diet (HFD) results in hyperlipidemia and an increase in oxidative stress. The purpose of this study was to investigate the preventive effect of embelin against hyperlipidemia and oxidative stress in HFD-induced obesity in rats. Male Wistar rats aged 12 weeks (150-200 g) were fed with an HFD for a period of 28 days to induce experimental obesity. HFD-induced obese rats were treated with embelin (50 mg/kg) or orlistat (10 mg/kg) for 21 days. A range of parameters were tested including body weight gain, body mass index (BMI), blood pressure, visceral fat pad weights, serum levels of glucose, insulin, leptin, apolipoprotein B (ApoB), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Twenty-one days of embelin (50 mg/kg) treatment produced effects similar to orlistat in reducing body weight gain, blood pressure, visceral fat pad weight, serum lipid levels, as well as coronary artery risk and atherogenic indices of HFD-fed rats. Embelin treatment also lowered the serum levels of glucose by 24.77 %, insulin by 35.03 %, and leptin by 43.39 %. Furthermore, embelin treatment significantly (p < 0.01) decreased the hepatic TBARS levels, while increasing the SOD, CAT, and GSH levels in obese rats. The present study indicated the preventive effect of embelin in HFD-induced obesity and its related complications. Embelin could be valuable in the development of new drug therapies to prevent obesity, hyperlipidemia, and oxidative stress.

Topics: Animals; Anti-Obesity Agents; Antioxidants; Benzoquinones; Diet, High-Fat; Embelia; Fruit; Humans; Hyperlipidemias; Lactones; Lipase; Lipid Metabolism; Male; Obesity; Orlistat; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar

1. The aim of the present study was to determine whether the addition of a subeffective dose of rimonabant (1 mg/kg) to orlistat would be beneficial in the treatment of diet-induced obesity in rats compared with orlistat monotherapy. 2. Male rats were divided into five groups: (i) rats fed a low-fat diet for 4 months; (ii) rats fed a high-fat diet (HFD) for 4 months and treated daily with vehicle (0.2% Tween-80 solution); (iii) orlistat (10 mg/kg per day)-treated HFD-fed rats; (iv) rimonabant (1 mg/kg per day)-treated HFD-fed rats; and (v) HFD-fed rats treated with a combination of orlistat plus rimonabant. Fasting blood glucose, serum insulin, leptin and adiponectin levels were measured. Liver and adiposity indices were calculated and liver and adipose tissues were processed for histological examination. 3. Over the 4 months of the study, vehicle-treated HFD-fed rats exhibited increased cumulative food intake, bodyweight and liver and adiposity indices. Moreover, vehicle-treated HFD-fed rats exhibited a deterioration in liver function and an abnormal lipid profile. Insulin resistance and serum leptin were increased in this group, whereas serum adiponectin levels were decreased. Orlistat monotherapy or combination therapy with orlistat plus rimonabant improved all these parameters. 4. The addition of the low subeffective dose of rimonabant to orlistat therapy ameliorated HFD-induced obesity to a much greater extent than orlistat monotherapy. This combination showed better weight control and metabolic profile compared with orlistat alone. Therefore, the results of the present study encourage reassessment of the use of a low dose of rimonabant to potentiate the effect of orlistat in the clinical management of obesity if proper clinical safety data are available.

Topics: Adiposity; Animals; Anti-Obesity Agents; Body Weight; Diet, High-Fat; Dose-Response Relationship, Drug; Drug Therapy, Combination; Lactones; Male; Obesity; Orlistat; Piperidines; Pyrazoles; Rats; Rats, Wistar; Rimonabant; Weight Gain

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

Topics: Adult; Anti-Obesity Agents; Behavior Therapy; Body Mass Index; Counseling; Female; Humans; Lactones; Male; Mass Screening; Obesity; Orlistat; United States; United States Food and Drug Administration

This study evaluated the anti-obesity effects of Phellinus baumii extract (PBE) in high-fat diet (HFD)-fed mice. Male 8-week-old C57BL/6 mice were randomly divided into four groups: control, normal chow diet plus vehicle; HFD-control, high-fat plus vehicle; HFD plus orlistat (Xenical(®), Roche, Basel, Switzerland) (50 mg/kg); and HFD plus PBE (500 mg/kg). PBE was administered daily by oral gavage for 12 weeks. Oral administration of PBE (500 mg/kg) significantly reduced body weight gain, hepatic lipid concentrations, and fat accumulation in epididymal adipocytes compared with mice fed HFD alone (P < .05). mRNA expression of genes related to triglyceride (TG) synthesis was suppressed in the PBE groups, and fatty acid synthase activity was also significantly inhibited (P < .05). Furthermore, we evaluated the effect of PBE on TG absorption and detected marked reduction in TG absorption in Xenical- and PBE-treated mice compared with the control group (P < .05). To determine the active compound of PBE, fractionation was conducted, and interfungin A, davallialactone, and hypholomine B were identified as the main compounds. Among the three identified compounds, as a representative compound, davallialactone was also shown to suppress fat accumulation in an in vitro model system. These anti-obesity and hypolipidemic effects appear to be partly mediated by suppressing plasma and hepatic fat accumulation through the inhibition of enzymes associated with hepatic and intestinal lipid absorption and synthesis.

Topics: Adipocytes; Adipose Tissue; Animals; Anti-Obesity Agents; Basidiomycota; Biological Products; Dietary Fats; Epididymis; Fatty Acid Synthases; Intestinal Absorption; Lactones; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Orlistat; Phytotherapy; Random Allocation; RNA, Messenger; Triglycerides; Weight Gain

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

This study evaluated the hypolipidemic and antiobesity effects of phloroacetophenone (2',4',6'-trihydroxyacetophenone, THA) isolated from Myrcia multiflora and their relationship with triglyceride (TG) intestinal absorption and pancreatic lipase activity inhibition. The hypolipidemic effect of THA was evaluated by acute (Triton WR-1339 treatment) and chronic assay (high-fat diet treatment), the antiobesity effect was evaluated by chronic assay (high-fat diet treatment), while the inhibition of enzymatic activity of pancreatic lipase was measured in the intestinal tissue of mice treated with high olive oil concentration. In the acute assay, THA caused greater total cholesterol (37 %) and triglyceride (46 %) serum level reduction than lovastatin (32 and 1 %), a HMG-CoA reductase inhibitor or orlistat (26 and 34 %), a gastrointestinal lipase inhibitor. In addition, in the chronic assay with a high-fat diet, THA reduced cholesterol and triglyceride levels (32 and 61 %, respectively) while lovastatin showed a decrease of 35 and 49 %, respectively. THA also caused a reduction in weight gain very similar to orlistat (40 and 38 %, respectively) when the animals were submitted to a high-fat diet. Moreover, THA showed a stronger and continuous pancreatic lipase inhibitory activity when compared with orlistat, causing inhibition of this enzyme during 6 hours associated to a significant reduction of triglyceride serum levels. The IN VIVO antiobesity and hypolipidemic effects of THA may be partly mediated by delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.

Topics: Acetophenones; Animals; Anti-Obesity Agents; Cholesterol; Diet, High-Fat; Glucosides; Hypolipidemic Agents; Intestinal Absorption; Lactones; Lipase; Lipids; Lovastatin; Male; Mice; Myrica; Obesity; Orlistat; Pancreas; Plant Extracts; Rats; Rats, Wistar; Triglycerides; Weight Gain

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

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

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

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

Both diet and medications are useful in the treatment of the obese patient. Weight loss of about 10% below baseline can be achieved with both, and there is no evidence that the composition of the diet, by itself, has any influence on weight loss. Presently only 1 drug is approved for long-term treatment of overweight patients, and its effectiveness is limited to palliation of the chronic disease of obesity. Combinations of medications and antidiabetic drugs that produce weight loss are being evaluated.

Topics: Adolescent; Adult; Anti-Obesity Agents; Antidepressive Agents, Second-Generation; Body Weight; Bupropion; Child; Drug Approval; Drug Combinations; Energy Intake; Exenatide; Female; Fructose; Humans; Hypoglycemic Agents; Islet Amyloid Polypeptide; Lactones; Male; Metformin; Naltrexone; Narcotic Antagonists; Obesity; Orlistat; Patient Compliance; Peptides; Randomized Controlled Trials as Topic; Sympathomimetics; Topiramate; United States; United States Food and Drug Administration; Venoms

Orlistat is a pancreatic lipase inhibitor licensed for the treatment of obesity. As obesity rates increase and non-prescription dispensing of orlistat increases, an awareness of its adverse effects is of crucial importance as complications arise more frequently from increased use. Orlistat induced pancreatitis has been described only once previously, but without a diagnostic increase in serum amylase.. We report the case of two patients who developed severe acute abdominal pain and elevated pancreatic enzymes at 2 and 10 days after starting orlistat. In one case no alterative precipitant was identified. In the other, a predisposing history of pancreatic injury was present. In both cases all other contributory causes were excluded.. Our reports suggest orlistat can trigger drug induced acute pancreatitis in certain patients. For patients presenting with abdominal pain soon after commencing orlistat, a diagnosis of pancreatitis must be considered. We also recommend cautious use of orlistat in patients at risk of pancreatic injury.

Topics: Acute Disease; Aged; Anti-Obesity Agents; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Pancreatitis

Oxyntomodulin (OXM) is a gut hormone released from intestinal L cell. Synthetic OXM and its analog reduce food intake and body weight in both rodents and human beings by being administered intravenously. However, people find intravenous administration difficult because of its side effects and inconvenience. The aim of this study is to develop a novel oral delivery system for OXM and its analog using genetically engineered Bifidobacterium as the carrier.. An OXM gene expression vector pBBADs-OXM for the Bifidobacterium genus was constructed. Human OXM sequence was fused with extracellular exo-xylanase (XynF) signal peptide (Xs) from Bifidobacterium longum under the control of the pBAD promoter. B. longum NCC2705 was transformed with the recombinant plasmid pBBADs-OXM by electroporation, and the transformed B. longum was selected using MRS plates containing 60 microg ml(-1) ampicillin. The OXM expression in vitro was identified by western blot and enzyme-linked immunosorbent assay (ELISA) assay after L-arabinose induction. Overweight BALB/c mice were treated with B. longum transformed with OXM after 0.2% L-arabinose induction every day for 4 weeks to investigate the effects of OXM-transformed B. longum on food intake and body weight by oral administration. The B. longum transformed with the green fluorescent protein (GFP) gene was used as negative control; orlistat, a gastrointestinal lipase inhibitor, was used as positive control; Normal saline (NS, 0.9% saline) was used as blank control. The food intakes of each group were measured every day, and body weights were measured once a week. Normal BALB/c (2 months old) mice were treated with OXM-transformed B. longum after induction by intragastric administration every day for 6 days to reveal the mechanism of transformed B. longum, with OXM exerting its biological function by oral administration. Plasma OXM, plasma ghrelin and the OXM of intestinal contents were detected by the ELISA method. Plasma glucose and triglyceride levels were analyzed using the Automatic Biochemistry Analyzer.. Transformed B. longum with OXM was selected and identified without biological and morphological alteration. An approximately 4-5 kDa OXM peptide was detected in both the supernatant and the cell pellet of transformed B. longum after L-arabinose induction in vitro. The food intake, body weight and blood triglyceride level of overweight mice treated with OXM-transformed B. longum were all significantly reduced compared with that of the GFP negative control group and NS control group (P<0.01). Interestingly, the plasma triglyceride level of the GFP group was significantly decreased compared with that of the NS control group (P<0.01). The OXM level in the intestinal contents of the OXM group was significantly increased compared with that of the GFP negative control group and the NS group (P<0.05). The plasma ghrelin level of the OXM group was significantly decreased compared with that of the GFP and NS groups (P<0.01). Unexpectedly, the ghrelin level of the GFP group was significantly increased compared with that of the NS control group (P<0.01).. A novel oral delivery system of Bifidobacterium for human OXM has been successfully established. The expression of recombinant OXM can be detected in the supernatant and cell pellet of transformed B. longum. OXM-transformed B. longum reduces food intake, body weight and plasma lipid level in overweight mice by oral administration.

Topics: Administration, Oral; Animals; Appetite Depressants; Bifidobacterium; Body Weight; Drug Carriers; Eating; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Lactones; Mice; Mice, Inbred BALB C; Obesity; Orlistat; Oxyntomodulin; Recombinant Proteins; Triglycerides

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: Adipose Tissue, White; Anti-Obesity Agents; Carcinoma, Hepatocellular; Diabetes Mellitus, Type 2; Fatty Acids; Humans; KATP Channels; Lactones; Leukemia; Liver Neoplasms; Obesity; Orlistat; Periodontitis

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

Obesity has become a major public health problem worldwide.. To examine the effect of orlistat in promoting weight loss and its specific effect on visceral adipose tissue and subcutaneous adipose tissue as evaluated by computed tomography.. A prospective case series study of 10 obese subjects was conducted. The 6 women and 4 men, age 50-67 years (mean 59 +/- 8 years), had a mean body mass index of 34.1 +/- 3.2 kg/m2. All subjects were prescribed a mildly hypocaloric diet (600 kcal/day deficit). In addition, all subjects were treated with orlistat 120 mg 3 times a day for 20.1 +/- 7 weeks.. The subjects had lost approximately 8.2 kg each, or 8.4% of their initial body weight. Mean body weight decreased from 98 +/- 13 to 89.8 +/- 13.6 kg at the last followup visit (P = 0.0001); mean BMI decreased from 34.1 +/- 3.2 to 30.3 +/- 3.9 kg/m2 (P = 0.0001), and mean waist circumference from 113.8 +/- 11.4 to 107.6 +/- 10 cm (P = 0.0006). Mean total abdominal adipose tissue volume, evaluated by computed tomography, decreased from 426 +/- 104.3 to 369.8 +/- 99.6 mm3 (P = 0.0001). Mean abdominal SAT volume decreased from 251.1 +/- 78.8 to 224 +/- 81.1 mm3 (P = 0.006), and mean abdominal VAT volume decreased from 176 +/- 76.7 to 141.6 +/- 67 mm3 (P = 0.0001). Thus, the total abdominal adipose tissue volume for the whole group decreased by 15.4%, and most of this decrease was attributable to the reduction in VAT (24.8%) as opposed to SAT (only 12% reduction) (P = 0.03). The weight reduction that occurred during the study was accompanied by a statistically significant reduction in levels of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and fasting blood glucose.. Our results demonstrate the effect of orlistat in reducing human visceral adipose tissue as evaluated by CT. The benefit of the treatment is further supported by the statistically significant reduction in cardiovascular risk factors.

Topics: Aged; Anti-Obesity Agents; Female; Humans; Imaging, Three-Dimensional; Intra-Abdominal Fat; Lactones; Male; Middle Aged; Obesity; Orlistat; Prospective Studies; Subcutaneous Fat; Tomography, X-Ray Computed

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

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

Topics: Adolescent; Anti-Obesity Agents; Child; Health Promotion; Humans; Lactones; Neuropeptide Y; Obesity; Orlistat; Young Adult

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; Appetite; Appetite Depressants; Body Weight; Cannabinoids; Drug Approval; Drug Industry; Humans; Lactones; Obesity; Orlistat; United States; United States Food and Drug Administration

Orlistat is a gastrointestinal lipase inhibitor approved for use in obesity. So far, no evidence has been reported on the use of orlistat in obese patients with coronary artery disease (CAD).. To investigate the effect of orlistat on body weight and lipid profiles in obese patients with CAD and hypercholesterolemia.. Thirty non-diabetic patients with CAD, body mass index (BMI) > or = 25 kg/m(2) and low-density lipoprotein cholesterol (LDL-C) > or = 2.6 and < 4.1 mmol/L were put on diet for 12 weeks. Those still having a BMI > or = 25 kg/m(2) received orlistat 120 mg thrice daily for another 24 weeks.. BMI was significantly reduced by 1.7% after 12 weeks of dietary treatment. The 24-week orlistat treatment resulted in further significant reduction in BMI (-2.8%) and LDL-C (-7.0%).. Diet and orlistat treatment significantly reduced BMI and improved LDL-C in obese patients with CAD and hypercholesterolemia.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Obesity Agents; Body Mass Index; Body Weight; Cholesterol, LDL; Coronary Artery Disease; Diet; Female; Hong Kong; Humans; Hypercholesterolemia; Lactones; Lipids; Male; Middle Aged; Motor Activity; Nutritional Status; Obesity; Orlistat; Prospective Studies; Risk Assessment

We report an unusual complication of orlistat, a gastrointestinal and pancreatic lipase inhibitor used in the treatment of obesity. A 66-year-old man with history of Type 2 diabetes and obesity presented to our hospital with recurrent episodes of hypoglycemia over 2 weeks. His medications included twice daily biphasic insulin and 3 months previously he was prescribed orlistat as treatment for his obesity. On admission he was in acute renal failure with a creatinine concentration of 405 micromol/l. His renal function 4 months previously was normal. Urinalysis revealed neither blood nor protein, but microscopy of his urine revealed moderate amounts of crystals. A renal biopsy revealed normal glomeruli, but there were features of acute tubular necrosis associated with oxalate crystal deposition. Over the next few days his renal function declined and needed hemodialysis. 3 weeks after his admission he continued to require hemodialysis and he unexpectedly had a cardiac arrest and died. Our patient had acute tubular necrosis secondary to orlistat-induced acute oxalate nephropathy. The identification of high risk patients treated with orlistat and regular monitoring of their renal function might reduce the risk of renal failure due to acute oxalate nephropathy.

Topics: Acute Kidney Injury; Aged; Anti-Obesity Agents; Calcium Oxalate; Diabetes Mellitus, Type 2; Fatal Outcome; Humans; Lactones; Male; Necrosis; Obesity; Orlistat

Advanced glycation end products (AGEs) formation is implicated in diabetic complications. Exogenous AGEs, namely glycotoxins, are present in certain foods and are absorbed from the gastrointestinal tract. Experimental data suggest that lifestyle interventions reducing their content in diet have beneficial effect.. Fourteen healthy (age: 42.14 +/- 12.38 years; body mass index [BMI]: 27.85 +/- 7.06 kg/m2) and ten women with type 2 diabetes (T2DM) (age: 48.70 +/- 9.31 years; BMI: 32.55 +/- 7.14 kg/m2) were enrolled in the study. A meal rich in AGEs was provided in a two-day protocol and on day 2, 240 mg of Orlistat were administered post-meal.. On day 1, serum AGEs levels showed a rise at 3 hours post-meal compared to baseline values in both groups (controls: 12.2%; P<0.001), T2DM: 2.6%; P=0.013), but at 5 hours post-meal only in the controls (control: 12.2%; P<0.001); T2DM: 1.9%; P=0.075). On day 2 at 3 hours post-meal control values showed a rise of 3.1% (P=0.003); T2DM of 1.9% (P=0.013); at 5 hours post-meal rise for controls was 4.6% (P=0.012); and for T2DM was 1.8% (P=0.009). The corresponding rise was significantly lower on day 2 only in controls at 3 and 5 hours post-meal (P=0.003; P=0.05, respectively).. Orlistat reduced the absorption of glycotoxins acutely and improved the metabolic profile in the control group, without an apparent beneficial effect in the diabetic group. The clinical significance of this observation should be further investigated in normal population, while in diabetics long-term studies may be required to demonstrate possible clinically significant effects.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Diet; Enzyme Inhibitors; Female; Glycation End Products, Advanced; Humans; Lactones; Middle Aged; Obesity; Orlistat; Postprandial Period

Topics: Anti-Obesity Agents; Drug Approval; Enzyme Inhibitors; Europe; Gastrointestinal Diseases; Humans; Lactones; Lipase; Obesity; Orlistat

Many consumers join online communities focused on health. Online forums are a popular medium for the exchange of health information between consumers, so it is important to determine the accuracy and completeness of information posted to online forums.. We compared the accuracy and completeness of information regarding the FDA-approved over-the counter weight-loss drug Alli (Orlistat) from forums and from clinicians.. We identified Alli-related questions posted on online forums and then posed the questions to 11 primary care providers. We then compared the clinicians' answers to the answers given on the forums. A panel of blinded experts evaluated the accuracy and completeness of the answers on a scale of 0-4. Another panel of blinded experts categorized questions as being best answered based on clinical experience versus review of the literature.. The accuracy and completeness of clinician responses was slightly better than forum responses, but there was no significant difference (2.3 vs. 2.1, p=0.5). Only one forum answer contained information that could potentially cause harm if the advice was followed.. Forum answers were comparable to clinicians' answers with respect to accuracy and completeness, but answers from both sources were unsatisfactory.

Topics: Consumer Health Information; Drug Information Services; Evidence-Based Medicine; Health Knowledge, Attitudes, Practice; Humans; Lactones; Obesity; Online Systems; Orlistat

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 associated with increased risk of conditions such as hypertension, dyslipidaemia, diabetes mellitus, and obstructive sleep apnoea. Pharmacotherapy for obesity should be considered in combination with lifestyle changes in obese patients, or overweight patients with other conditions that put them at risk of developing heart disease. Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use. Sibutramine is a serotonergic and adrenergic drug that reduces food intake. Orlistat is a gastrointestinal lipase inhibitor that interferes with fat absorption. However, it commonly causes flatulence and diarrhoea. Rimonabant is the first of a series of endocannabinoid receptor antagonists. It was approved by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMEA) as an adjunct to diet and exercise in treating obesity in 2006. However, despite the extensive clinical trial data, EMEA announced in 2008 that it has recommended suspension of rimonabant because of its psychiatric side effects. Studies evaluating the long-term safety and efficacy of anti-obesity agents are needed.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Body Weight; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Lactones; Lipase; Meta-Analysis as Topic; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Time Factors

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

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

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

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

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

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

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

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

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

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

The XENDOS study showed that behavioural and pharmacological therapy can decrease the risk of metabolic disorders in obese patients.. A probabilistic Bayesian Markov model simulating the outcomes of orlistat treatment on the obese Italian population has been developed with the WinBUGS software. The model integrates an algorithm to estimate cardiovascular risk based on Framingham Heart Study equations. Analyses adopted the societal cost perspective, including direct medical costs borne by both the National Health Service and the patient, since orlistat is not included in the Italian reimbursement list.. The simulation on the Italian obese population estimated an average increase in quality-adjusted life expectancy, a reduction of cardiovascular events and new diabetes cases. The average incremental cost-utility ratio is euro75.3 (7.6-180.6) x 1000/QALY. The subgroup analysis showed that the benefits are relatively greater in older patients and in patients with impaired glucose tolerance (IGT). Two hypotheses have been explored to estimate the impact of a potential reimbursement decision by the Italian NHS: (1) orlistat is given to every obese patient; (2) orlistat is given only to obese IGT patients with a previous glucose tolerance general screening program to assess their eligibility. The cost utility of the strategies are euro42.3 (-22.16-108.7) and euro10.16 (-60.4-38.76) x 1000/QALY, respectively.. Orlistat shows a good pharmacoeconomic profile and, in particular, the strategy of a screening programme to identify and treat the IGT subgroup has a cost-utility value of about euro10000/QALY. This value is lower than that of several therapeutic strategies commonly accepted and reimbursed in developed countries.

Topics: Aged; Anti-Obesity Agents; Bayes Theorem; Computer Simulation; Female; Health Care Costs; Humans; Italy; Lactones; Male; Markov Chains; Middle Aged; Models, Biological; Obesity; Orlistat; Placebos; Prevalence; Quality of Life; Risk Reduction Behavior; Treatment Outcome

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

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

Topics: Adult; Anti-Obesity Agents; Child; Diet, Reducing; Humans; Lactones; Obesity; Orlistat

Topics: Acute Disease; Anti-Obesity Agents; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Pancreatitis

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

Our study estimated the cost-effectiveness of pharmacologic treatment of obesity in combination with a low-calorie diet in The Netherlands.. Costs and effects of a low-calorie diet-only intervention and of a low-calorie diet in combination with 1 year of orlistat were compared to no treatment. The RIVM Chronic Disease Model was used to project the differences in quality adjusted life years (QALYs) and lifetime health-care costs because of the effects of the interventions on body mass index (BMI) status. This was done by linking BMI status to the occurrence of obesity-related diseases and by relating quality of life to disease status. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. In univariate sensitivity analysis, we assessed how sensitive the results were to several key assumptions.. Incremental costs per QALY gained were Euro 17,900 for the low-calorie diet-only intervention compared to no intervention and Euro 58,800 for the low-calorie diet + orlistat compared to the low-calorie diet only. Assuming a direct relation between BMI and quality of life, these ratios decreased to Euro 6000 per QALY gained and Euro 24,100 per QALY gained. Costs per QALY gained were also sensitive to assumptions about long-term weight loss maintenance.. Cost-effectiveness ratios of interventions aiming at weight reduction depend strongly on assumptions regarding the relation between BMI and quality of life. We recommend that a low-calorie diet should be the first option for policymakers in combating obesity.

Topics: Adult; Aged; Anti-Obesity Agents; Caloric Restriction; Combined Modality Therapy; Cost-Benefit Analysis; Humans; Lactones; Middle Aged; Models, Economic; Obesity; Orlistat; Quality-Adjusted Life Years; Young Adult

Topics: Acute Kidney Injury; Anti-Obesity Agents; Biopsy; Disease Progression; Female; Follow-Up Studies; Glucocorticoids; Humans; Kidney; Lactones; Lipase; Middle Aged; Obesity; Orlistat; Ultrasonography

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

Nonalcoholic steatohepatitis (NASH) may cause progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment, thus far, has been restricted to diet and weight loss, but without compelling results. In this study we aimed to evaluate the efficacy of orlistat therapy in obese patients with NASH. Fourteen obese patients with NASH underwent liver biopsy prior to and subsequent to 6 months treatment with orlistat (120 mg tid). Hepatic fat extension was graded as normal, mild, moderate, or severe. Hepatic fibrosis was scored on a scale from 0 to 4, with 0 denoting no fibrosis and 4, cirrhosis. Portal inflammation was scored as 0-3, with 0 = normal, 1 = mild, 2 = moderate, and 3 = severe inflammation. Fourteen patients had NASH associated with diabetes, hyperlipidemia, or obesity. Orlistat reduced fatty infiltration in 10 patients (70%; P<0.01), 3 of whom had normal liver fat content after treatment. Orlistat improved inflammatory activity by 2 grades in 28% and by 1 grade in 50% of patients and effected no change in 22% of patients. Five patients (35%) returned to normal inflammatory activity. Orlistat improved hepatic fibrosis by 2 grades in three patients (21%) and by 1 grade in seven patients (50%). There was no change in four patients (28%). Orlistat lowered aminotransferases levels, total cholesterol, triglycerides and low-density lipoprotein, respectively. Insulin resistance index and malonyl dialdehyde levels improved significantly after orlistat therapy, whereas HbAic remained unchanged. In conclusion, in obese patients with NASH, liver fibrosis and inflammation improved after therapy with orlistat.

Topics: Adult; Biopsy; Body Mass Index; Enzyme Inhibitors; Fatty Liver; Female; Follow-Up Studies; Humans; Lactones; Lipase; Liver Cirrhosis; Male; Middle Aged; Obesity; Orlistat; Recovery of Function; Severity of Illness Index; Transaminases; Treatment Outcome

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

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

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

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

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

Topics: Acute Kidney Injury; Anti-Obesity Agents; Biopsy; Cohort Studies; Disease Progression; Follow-Up Studies; Glucocorticoids; Humans; Kidney; Lactones; Lipase; Obesity; Orlistat; Treatment Outcome; Ultrasonography

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

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

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

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

Topics: Anti-Obesity Agents; Humans; Lactones; Life Style; Nonprescription Drugs; Obesity; Orlistat

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

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

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

Our objective was to examine patients' experiences of taking orlistat as a means to explore adherence and behavior change.. We performed qualitative interviews with 12 participants who had taken orlistat in the past 2 years.. Their experiences were described in terms of beliefs about the causes of their obesity, their motivations for taking orlistat, and highly visual side effects. These themes have implications for understanding adherence and behavior change. For some, the side effects led to nonadherence and absence of behavior change. These individuals seemed to be motivated by routine effects of being overweight, such as lowered self-esteem. In contrast, those who were motivated by a life crisis seemed to tolerate the side effects of the drug, leading to adherence. In turn, these highly visual side effects enabled them to make an explicit link between food consumed and weight, creating a shift in their beliefs about the causes of obesity and making behavior change more likely.. Orlistat use illustrates how treatment and illness beliefs interact to create both adherence and behavior change, particularly in the context of a life crisis and particularly when symptoms can be visualized.

Topics: Adult; Anti-Obesity Agents; Culture; Feeding Behavior; Female; Humans; Interviews as Topic; Lactones; Male; Middle Aged; Motivation; Obesity; Orlistat; Patient Compliance; Self Concept; Surveys and Questionnaires

Obesity is a frequent complication following liver transplantation and is insufficiently responsive to dietary and life style advice. We studied the safety of orlistat treatment in obese and overweight liver transplant recipients (n = 15) on a stable tacrolimus-based immunosuppressive regimen. For safety reasons, the treatment period was restricted (6 months 120 mg t.i.d., 3 months 120 mg daily). Three patients dropped out, tacrolimus dose was adjusted in six of 12 remaining patients (dose reduction in 4, increase in 2, P = N.S.). All dose adjustments occurred during the 6 months of orlistat 120 mg t.i.d. therapy. No drug intolerance, adverse events or episodes of rejection occurred during the study. Efficacy of orlistat treatment in this population could not be shown, because a formal control population was not included in this safety trial. Moreover, only a significant decrease of waist circumference (P < 0.01 versus start of the study), but not of weight or body mass index, was achieved in the treated group. Orlistat treatment is well tolerated in liver transplant recipients and can be started safely, provided immunosuppressive drug levels and dietary adherence are closely monitored.

Topics: Adult; Aged; Anti-Obesity Agents; Drug Interactions; Female; Humans; Lactones; Lipids; Liver Transplantation; Male; Middle Aged; Obesity; Orlistat; Overweight; Pilot Projects; Prospective Studies; Tacrolimus

Topics: Adolescent; Anti-Obesity Agents; Anticonvulsants; Drug Interactions; Drug Monitoring; Epilepsy; Female; Humans; Intestinal Absorption; Lactones; Lamotrigine; Obesity; Orlistat; Triazines

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

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

Topics: Anti-Obesity Agents; Antineoplastic Agents; Base Sequence; Cell Cycle; Cells, Cultured; DNA; Enzyme Inhibitors; Fatty Acid Synthases; Gastrointestinal Neoplasms; Gene Expression; Genes, erbB-2; Humans; Lactones; Obesity; Orlistat; Receptor, ErbB-2

To assess the cost-effectiveness of orlistat plus a calorie-controlled diet compared with a calorie-controlled diet alone for the treatment of overweight and obese patients in Ireland.. Economic modelling techniques using published international efficacy data and Irish cost data were used to estimate the cost-effectiveness of orlistat in obese patients when only responders to treatment (ie achieve 5% weight loss after 3 months of treatment) continue orlistat after 3 months. The model incorporated known relationships between weight loss and quality of life (utility) gain, and weight loss and reduction in risk of type 2 diabetes (T2DM) to predict the impact of weight loss on quality-adjusted-life-years (QALYs) gained and on the onset of T2DM. The costs associated with each treatment arm included the acquisition cost of orlistat, cost of a calorie-controlled dietary programme and monitoring and treatment costs associated with T2DM. An Irish health-care perspective was taken for the analysis, based on 2003 costs.. Weight loss data on 1386 patients from five pivotal orlistat clinical trials with at least 12 months duration were pooled (two American and three primarily European studies). All the studies were randomized, placebo-controlled, multicentre trials with a similar design. The inclusion criteria were BMI > or =28 kg / m(2), age > or =18 y, no diagnosed T2DM and the ability to lose 2.5 kg in weight during the introductory period.. Cost effectiveness was modelled from these data and presented as incremental cost per QALY.. When orlistat treatment plus a calorie-controlled diet was compared with a calorie-controlled diet alone, the incremental cost per year was euro 478. The number needed to treat (NNT) to gain one QALY was estimated to be 35. The incremental cost per QALY gained was within the range considered cost-effective at euro 16,954. Sensitivity analysis demonstrated an incremental cost per QALY of euro 11,000-35,000 under a variety of assumptions.. Our model suggests that orlistat is effective and cost-effective in obese patients, if after 3 months of treatment, only treatment responders continue treatment.

Topics: Adult; Anti-Obesity Agents; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Humans; Ireland; Lactones; Models, Economic; Obesity; Orlistat; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Single-Blind Method; Treatment Outcome

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

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

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

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

This study aimed to assess the cost utility of orlistat treatment based on (i) criteria from recent guidance from the National Institute for Clinical Excellence (NICE) for England and Wales (treatment discontinued if weight loss < 5% at 3 months; and < 10% at 6 months); and (ii) alternative criteria from the European Agency for the Evaluation of Medicinal Products (EMEA) licence for orlistat prescription in the European Community (treatment discontinued if weight loss < 5% at 3 months). Subjects were 1398 obese individuals who participated in three large European Phase III trials of orlistat treatment for adults (BMI: 28-47 kg m(-2)). Measures were: response to treatment in orlistat and placebo treatment groups; health benefit expressed as quality adjusted life years (QALYs) gained associated with weight loss; costs associated with orlistat treatment. In the cost utility model with multiway sensitivity analysis, the cost/QALY gained using the NICE criteria was estimated to be 24,431 pounds (sensitivity analysis range: 10,856 to 77,197 pounds). The cost/QALY gained using the alternative EMEA criteria was estimated to be 19,005 pounds (range: 8,840 to 57,798 pounds). In conclusion, NICE guidance for the continued use of orlistat was supported in this updated cost utility model, comparing favourably with a previously published estimate of 45,881 pounds per QALY gained. Moreover, the value for money of orlistat treatment is improved further if EMEA treatment criteria for continued orlistat treatment are applied. The EMEA criteria should be considered in any future changes to the NICE guidance or in guidance issued by similar agencies.

Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Humans; Lactones; Obesity; Orlistat; Quality-Adjusted Life Years

Topics: Adult; Anti-Obesity Agents; Chronic Disease; Clozapine; Humans; Hyperglycemia; Lactones; Male; Obesity; Orlistat; Schizophrenia

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

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

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

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

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

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

To study effects of xenical combined with moderately hypocaloric diet on fat tissue mass, carbohydrate and lipid metabolism in patients with metabolic syndrome.. The study included 60 patients with body mass index (BMI) over 30 kg/m2, mild and moderate arterial hypertension, dyslipidemia, impaired glucose tolerance (IGT) and diabetes mellitus (DM) type 2. The patients were divided into two groups. 30 patients of group 1 received xenical in a dose 120 mg 3 times a day for 24 weeks. 30 patients of the control group received only the above diet for 24 weeks. The examination included 24-h monitoring of arterial pressure, anthropometric measurements, tests for glycemia, C-peptide, cholesterol, triglycerides (TG), LDLP, HDLP.. Group 1 patients reduced their weight by 10.8 +/- 7.5 kg and fat tissue mass by 9.4 +/- 9.2 kg. This was in correlation with improvement of fatty, carbohydrate metabolism, arterial pressure. After 24 weeks of therapy xenical lowered cholesterol by 15%, LDLP cholesterol by 20%, TG by 28%, systolic and diastolic pressure by 5 and 4%.. Combination of xenical with hypocaloric diet can be used in therapy of patients with metabolic syndrome.

Topics: Anti-Obesity Agents; Blood Pressure; Body Weights and Measures; Female; Humans; Insulin Resistance; Lactones; Lipids; Male; Obesity; Orlistat; Treatment Outcome

In eukaryotes, fatty acid synthase (FAS) is the enzyme responsible for synthesis of palmitate, the precursor of long-chain nonessential fatty acids. FAS is up-regulated in a wide range of cancers and has been suggested as a relevant drug target. Here, two independent approaches are taken toward knocking down FAS and then probing its connection to tumor cell proliferation. In one approach, Orlistat, a drug approved for treating obesity, is used as a potent inhibitor of the thioesterase function of FAS. In a separate strategy, the expression of FAS is suppressed by targeted knock-down with small interfering RNA. In both circumstances, the ablation of FAS activity causes a dramatic down-regulation of Skp2, a component of the E3 ubiquitin ligase that controls the turnover of p27Kip1. These effects ultimately tie into the retinoblastoma protein pathway and lead to a cell-cycle arrest at the G1/S boundary. Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins.

Topics: Avidin; Biotin; Blotting, Western; Cell Cycle; Cell Cycle Proteins; Cell Division; Cell Line; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p27; Dose-Response Relationship, Drug; Down-Regulation; Epithelial Cells; Fatty Acid Synthases; Fatty Acids; G1 Phase; Humans; Lactones; Lipase; Obesity; Orlistat; Palmitic Acid; Retinoblastoma Protein; RNA, Small Interfering; S Phase; S-Phase Kinase-Associated Proteins; Serine Endopeptidases; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors; Tumor Suppressor Proteins; Ubiquitin; Ubiquitin-Protein Ligases

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

The study was undertaken to examine the nature and degree of postprandial lipemia during routine food fat loading (FFL) in young obese patients and the possible ways of correcting excessive body mass (BM) and hormonally metabolic disturbances. Fifty obese patients aged 18 to 25 years were examined. Group 1 comprised 20 patients with the BM index (BMI) of 33.4 +/- 0.8 kg/m2; Group 2 included 30 patients with the BMI of 33.05 +/- 5.22 kg/m2. The conventional glucose tolerance test was performed in all the examinees, by determining the degree of glycemia, the levels of immunoreactive insulin, and the insulin-resistance index (IRI). With FFL, lipid profile trends were studied in Group 1 patients. Before and 6 months after xenical therapy, anthropometric, lipid and carbohydrate metabolic parameters were determined and BMI was calculated in Group 2 patients. Group 1 patients were found to have impaired tolerance to FFL as compared with the control group. Postalimentary lipemia was accompanied by atherogenic changes in hormonally metabolic parameters. During xenical therapy, Group 2 patients were found to have positive changes in all anthropometric parameters, including those characterizing abdominal obesity, as well as normalized basal hyperinsulinemia, diminished stimulated insulinemia, increased insulin sensitivity, improved blood lipid profile with decreased atherogenic changes. Thus, the study has revealed that young obese patients show impaired fat tolerance with normal glucose tolerance. For therapy of obesity in young individuals, xenical may be recommended as an agent that not only decreases BM, but also improves hormonally metabolic parameters.

Topics: Adolescent; Adult; Anti-Obesity Agents; Body Mass Index; Dietary Fats; Female; Humans; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Risk Factors

Topics: Anti-Obesity Agents; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Humans; Lactones; Obesity; Orlistat; Peptide Fragments; Postprandial Period; Protein Precursors

While the intentional modification of eating habits remains the most important measure for losing weight, pharmacological support, in particular with regard to the long-term outcome, can be helpful. Catacholaminergic substances, such as diethylpropion and phenylpropanolamine are restricted by their side effects to short-term application only, and their use makes little sense. The serotoninergic substance sibutramine, which acts on the central nervous system to curb the appetite or enhance the feeling of saturation, and orlistat, which inhibits the assimilation of fat from the bowel, are approved for longer-term treatment of obesity, and lead to an additional loss of 3-5% of the patient's initial weight after one year of use. Thereafter, however, this benefit decreases. Further substances involving new, possibly combinable, approaches are currently under development.

Topics: Appetite Depressants; Caloric Restriction; Clinical Trials as Topic; Combined Modality Therapy; Follow-Up Studies; Humans; Lactones; Lipase; Obesity; Orlistat; Treatment Outcome

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

An overweight 56-year-old type II diabetic on peritoneal dialysis (body mass index 35 kg/m(2)) was taking Orlistat for some months up until live-unrelated renal transplantation. Despite oral cyclosporin A (CyA) for 48 hours pretransplantation, it was very difficult to achieve adequate CyA blood levels for the first week postengraftment despite the use of much larger oral CyA doses. After opening his bowels on day 7, and the use of 3 days intravenous CyA, good CyA blood levels were achieved then maintained with conventional oral doses. The authors believe that this case shows important interactions between CyA and Orlistat.

Topics: Administration, Oral; Anti-Obesity Agents; Cyclosporine; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Immunosuppressive Agents; Injections, Intravenous; Kidney Failure, Chronic; Kidney Transplantation; Lactones; Male; Middle Aged; Obesity; Orlistat

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

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

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

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

To estimate the economic value of pharmacological treatment of type 2 diabetes mellitus in overweight and obese patients using orlistat in addition to standard diabetes therapy (i.e., a sulphonlyurea, metformin or insulin) and weight management strategies as compared with standard diabetes therapy and weight management strategies alone in a US-based healthcare setting. The perspective of the study was from the viewpoint of a US healthcare provider.. Markov state transition model simulating diabetes-related complications and mortality for a period of 11 years. Patients were modelled to continue orlistat therapy for a 52-week period, assuming a 3-year period of weight regain where after 3 years bodyweight would match that of the placebo group. The impact of orlistat on glycosylated haemoglobin (HbA(1c)) values was evaluated directly using data from four randomised, placebo-controlled, 1-year trials of orlistat in overweight or obese adults with type 2 diabetes who also received standard diabetes pharmacotherapy and intensive lifestyle modification. Incidence rates of micro- and macrovascular complications associated with type 2 diabetes and the estimated relative reduction in incidence rates associated with a decrease in mean updated HbA(1C) values were derived from the United Kingdom Prospective Diabetes Study (UKPDS) estimates for a reference population of male patients, 52 years of age. US cost estimates were derived from published sources and presented in 2001 US dollars. Discounting of 3% was applied. Probabilistic sensitivity analysis was applied to evaluate the robustness of the results of the persistence of the effect of orlistat after treatment.. Average costs and event-free life-years gained during the 11-year period expressed as the incremental costs divided by the incremental gain in life expectancy.. Treatment with orlistat, 120 mg three times daily, increased event-free life expectancy by 0.13 years over an 11-year period. Average treatment costs were estimated to be 19,987 US dollars in the orlistat group compared with 18,865 US dollars in the group that received diabetes medication and weight management alone. This translated into a cost-effectiveness ratio of 8327 US dollars per event-free life-year gained.. Adding orlistat as a pharmacological treatment to conventional diabetes and weight management approaches seems to be a cost-effective treatment option for overweight and obese patients with type 2 diabetes.

Topics: Anti-Obesity Agents; Body Weight; Cost-Benefit Analysis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Health Care Costs; Humans; Hypoglycemic Agents; Lactones; Male; Markov Chains; Models, Economic; Obesity; Orlistat; Randomized Controlled Trials as Topic; United States

Nonalcoholic steatohepatitis is now recognized as a common chronic liver disorder. Up to 16% of affected patients may progress to cirrhosis. The incidence and prevalence of this disease are noted to be increasing, in parallel with the nationwide increase in obesity and diabetes. Treatment options for these patients remain quite limited, however. Weight reduction has been advocated, but there are little data to support this practice, as most patients are unable to comply with the proper dietary modifications. We report three obese patients with biopsy-proven nonalcoholic steatohepatitis treated for 6-12 months with a weight reduction medication, orlistat, who lost between 22-42 lb, and had significant clinical and histopathological improvement on follow-up.

Topics: Adult; Anti-Obesity Agents; Fatty Liver; Female; Hepatitis; Humans; Lactones; Middle Aged; Obesity; Orlistat

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

This study investigated orlistat treatment in obese prepubertal children with regard to tolerance, safety and psychological well-being.. 11 healthy, severely obese prepubertal children (age 8.3-12.3 y, body mass index standard deviation score 5.3-9.2) were recruited for a 12 wk open treatment. Before, during and after treatment, the participants were investigated by psychological evaluation, blood chemistry, and parameters reflecting obesity and fat mass.. The participants were able to comply with the treatment, as indicated by pill counts and self reports, and expressed a desire to continue the treatment after the study period. Gastrointestinal side effects were mild and tolerable. No negative effects on psychological or physical well-being were detected, and the psychological evaluation demonstrated increased avoidance of fattening food, body shape preoccupation and oral control (p = 0.011). The median weight loss was 4.0 kg (range -12.7 to +2.5 kg, p = 0.016) and was highly correlated to decreased fat mass (regression coefficient 0.953, p < 0.01).. This pilot study indicates that obese prepubertal children were able to reduce their fat intake to avoid gastrointestinal side effects. Thus, orlistat may be suitable as a component in behaviour-modification programmes for obese children, and the results prompt a placebo-controlled investigation of its effectiveness in promoting weight loss.

Topics: Absorptiometry, Photon; Anthropometry; Anti-Obesity Agents; Child; Female; Gonadotropins; Humans; Lactones; Lipids; Liver; Male; Obesity; Orlistat; Patient Compliance; Pilot Projects

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

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

Pharmacists, especially those in community practice, should increase their level of intervention in dealing with the nationwide epidemic of obesity since they interact with large numbers of the public on a regular basis. We hypothesized that patients who receive medication for weight loss may have an improved therapeutic outcome if they received additional support from their community pharmacist.. To evaluate the impact of pharmacist support on patient persistence with orlistat.. Pharmacists were trained in basic obesity management skills. Patients who were prescribed orlistat and attending an outpatient nutrition program were invited to participate in the study. All patients agreed to receive pharmaceutical care. Those who lived where the service was available were assigned to the intervention (I) group and those who did not were assigned to the control (C) group. All patients received usual care provided by the outpatient clinic.. Thirty patients, 15 in the I group and 15 in the C group, were recruited. Both groups were predominantly women (87%) with a mean +/- SD age of 43.8 +/- 9.7 years. Patients in the I group had significantly greater persistence with orlistat therapy as assessed by duration of therapy (p = 0.006) and number of patients completing the 26-week study (7 I, 2 C; p = 0.046). There was no significant difference in percent of weight loss between groups (p > 0.05).. In this pilot study, patients receiving pharmaceutical care took orlistat longer than the controls and had improved outcome with orlistat therapy.

Topics: Adult; Anti-Obesity Agents; Community Pharmacy Services; Drug Administration Schedule; Female; Humans; Lactones; Male; Obesity; Orlistat; Patient Compliance

Numerous referrals to our Obesity Unit state that 'treatment with Orlistat did not work'. This surprised us, since Orlistat has been well documented to result in long-term sustained moderate weight loss. A simple questionnaire to 70 such patients, however, revealed that in many cases the referral physician had not observed basic rules and regulations, nor given appropriate information on Orlistat use.

Topics: Adult; Anti-Obesity Agents; Clinical Competence; Female; Health Surveys; Humans; Lactones; Male; Obesity; Orlistat; Primary Health Care; Treatment Failure

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

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Dietary Fats; Enzyme Inhibitors; Humans; Lactones; Life Style; Lipase; Obesity; Orlistat; Time Factors

To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents.. Prospective, open-label pilot study.. Warren Grant Magnuson Clinical Center of the National Institutes of Health.. Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition.. Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 microg.. During 3-6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation.. It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.

Topics: Adolescent; Analysis of Variance; Avitaminosis; Child; Female; Humans; Lactones; Male; Obesity; Orlistat; Pilot Projects; Prospective Studies; Vitamin A; Vitamin D; Vitamin E

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

Topics: Cost-Benefit Analysis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Lactones; Obesity; Orlistat

Topics: Adult; Anti-Obesity Agents; Humans; Lactones; Male; Obesity; Orlistat; Skin; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Adult; Anti-Obesity Agents; Evidence-Based Medicine; Humans; Lactones; Obesity; Orlistat; Prognosis; Risk Factors

Obesity is a common condition in type 2 diabetic patients. Treating obesity may enhance hypoglycemic treatment and contribute to the reduction of long-term microvascular and macrovascular complications. Orlistat reduces cardiovascular risk factors in obese type 2 diabetic patients. The objectives of this study were to estimate the long-term clinical consequences of this weight loss and the resulting cost-effectiveness of treating obese type 2 diabetic patients with orlistat.. A Markov model was developed to predict, over a 10-year period, the complication rates and mortality with and without a 2-year orlistat treatment, assuming a 5-year catch-up period after treatment. A stepwise approach was used to obtain the clinical data. First, the impact of weight loss with orlistat on HbA(1c), blood pressure, and cholesterol was assessed; then, the impact on mortality and micro- and macrovascular complications of decreasing these risk factors was applied. Four subgroups were studied based on the presence of risk factors.. Cost-effectiveness varies between 3,462 Euro/life-year gained (LYG) for obese diabetic patients with hypertension and hypercholesterolemia and 19,986 Euro/LYG for obese diabetic patients without other risk factors. The latter result is not robust according to sensitivity analyses.. Our results suggest that orlistat is cost-effective in the management of obese type 2 diabetic patients, especially in those with the presence of hypercholesterolemia and/or hypertension. Evidence on longer-term benefits of orlistat (>2 years) will be of importance for future decision-making.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Hypercholesterolemia; Hypertension; Lactones; Markov Chains; Models, Econometric; Obesity; Orlistat; Risk Factors; Time

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

The simultaneous launch of orlistat and sildenafil in 1998 provoked much media attention, particularly around the role of lifestyle drugs and their potential costs if controls were not established. Fears were also expressed that primary care would be overwhelmed by demand, and little information was available about the attitude of GPs to their new role as prescribers of lifestlye drugs. Partly in response to these concerns, tight prescribing guidelines and licensed indications, for sildenafil and orlistat, respectively, were issued.. Our aim was to describe levels of demand for orlistat and sildenafil in general practice, whether this demand was translated into a prescription, adherence to prescribing guidelines/licensed indications and the GP perception of appropriateness of an NHS prescription for either of these drugs.. We carried out an observational study in primary care conducted over a 6-week period during 1999. Twenty-seven GPs were recruited, each from a different practice. All GP consultations were recorded for the study period and the GP completed a structured questionnaire each time sildenafil or orlistat were discussed in a consultation.. Sildenafil was discussed in 0.5% (68/13 394) of consultations and orlistat in 0.3% (42/13 394). GPs thought that a corresponding NHS prescription would be highly appropriate in 57 and 74% of cases, respectively, although for both lifestyle drugs, nearly 20% of GPs thought such prescriptions were inappropriate. An NHS prescription was issued in 43% of consultations in which sildenafil had been discussed and 33% in which orlistat had been discussed. Five out of 29 NHS sildenafil prescriptions were issued to patients failing to fulfil the requirements of prescribing guidelines; similarly, one out of 14 orlistat prescriptions fell outside licensed indications. There were four examples of NHS prescriptions for sildenafil which were given even when the GP thought the drug to be inappropriate, whereas orlistat was never given when the GP thought it inappropriate.. Levels of demand for the two lifestyle drugs, sildenafil and orlistat, were modest when compared with earlier media predictions. Neither was there evidence that GP was pitted against patient in their negotiation concerning a lifestyle drug NHS prescription since most GPs agreed with their patients that such a prescription was appropriate. Prescribing guidelines and licensed indications were generally adhered to, but the modest level of demand raises questions about expanding the guidelines for sildenafil.

Topics: Anti-Obesity Agents; Attitude of Health Personnel; Drug Prescriptions; Drug Utilization; England; Erectile Dysfunction; Family Practice; Female; Health Services Needs and Demand; Humans; Lactones; Life Style; Male; Obesity; Orlistat; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

It can be tough getting patients to take their medicines as prescribed, particularly when there are side-effects or other barriers involved. To get around this problem, Roche decided to develop a DM approach to guide patients taking the organization's new weight-loss agent, XENICAL. In place now for 15 months, the telephonic program is boosting compliance and getting the intended results.

Topics: Anti-Obesity Agents; Counseling; Disease Management; Drug Industry; Humans; Lactones; Obesity; Orlistat; Patient Compliance; Patient Education as Topic; Reimbursement Mechanisms; Self Administration; Social Support; Telephone

Topics: Anti-Obesity Agents; Combined Modality Therapy; Contraindications; Diet, Reducing; Drug Monitoring; Humans; Lactones; Obesity; Orlistat; Patient Education as Topic; Patient Selection; Treatment Outcome

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; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat; Practice Guidelines as Topic; Technology Assessment, Biomedical

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

Topics: Adolescent; Anti-Obesity Agents; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diet, Reducing; Female; Humans; Lactones; Obesity; Orlistat; Weight Gain

Most antiobesity drugs act centrally to reduce appetite or increase satiety. Orlistat is the first in a new class of drugs targeted at a single dietary component, in this case dietary fat.. To review the clinical actions and efficacy of orlistat and to discuss its place in overall weight management.. Orlistat is best used in long term weight management as an adjunct to dietary modification and increased physical activity. The reduction in fat absorption results in a slow but sustained weight reduction and improved metabolic parameters such as reduced total, and LDL cholesterol. Side effects are minimised by maintaining a low fat diet.

Topics: Anti-Obesity Agents; Australia; Avitaminosis; Cholesterol; Humans; Lactones; Obesity; Orlistat

Topics: Alopecia; Anti-Obesity Agents; Enzyme Inhibitors; Erectile Dysfunction; Family Practice; Finasteride; Humans; Lactones; Male; Obesity; Orlistat; Piperazines; Purines; Sildenafil Citrate; Sulfones

In most clinical trials it is problematic to recruit enough patients within a reasonable time period. Prolonged or inefficient recruitment or both can have negative scientific and economic consequences. The XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study is an ongoing randomized, double-blind, placebo-controlled, prospective, multicenter trial investigating whether orlistat combined with hypocaloric diet and moderate physical exercise can reduce the incidence of diabetes in obese subjects. To implement the XENDOS protocol and recruit the study patients, we designed a system for centralized patient recruitment and centralized scheduling of patients and staff at the 22 collaborating centers. The recruitment and inclusion phase was divided into a series of different consecutive examinations of increasing complexity. Relatively simple initial examinations enabling a large throughput of patients were followed by more detailed examinations of fewer subjects, by then known to fulfil some of the study-specific requirements. With the aid of object-oriented techniques, the software was modularized to enable concurrent engineering. We also selected a structure where plug-in modules handling specific tasks could be added to the system as needed. The design was supported by a flow-oriented view of the progress of the patients through the study. With this overall solution we managed to include 3305 subjects (98.8% of the requested number) within less than 4 months. The sex distribution (44.8% men) and the number of patients with impaired glucose tolerance (IGT), (21.1%) were in close accordance with, or far better than, the requirements of the protocol (45% men, at least 10% IGT patients). The basic design of the XENDOS information system can be adapted to fulfil the requirements of other study protocols within the fields of obesity, diabetes, hypertension, coronary heart disease, etc. Shortening the recruitment and inclusion phase of large clinical trials is of great value both to be medical society and the pharmaceutical industry.

Topics: Adult; Anti-Obesity Agents; Diabetes Mellitus; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Orlistat; Patient Selection; Randomized Controlled Trials as Topic; Sweden

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

Topics: Adult; Anti-Obesity Agents; Drug Monitoring; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Patient Compliance

Topics: Adult; Anti-Obesity Agents; Depression; Female; Humans; Lactones; Obesity; Orlistat

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

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

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

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

Topics: Absorption; Cyclosporine; Humans; Lactones; Obesity; Organ Transplantation; Orlistat

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

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

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

Topics: Anti-Obesity Agents; Cardiology; Diabetes Mellitus; Humans; Lactones; New York City; Obesity; Orlistat

Topics: Anti-Obesity Agents; Body Weight; Double-Blind Method; Enzyme Inhibitors; Family Practice; Female; Humans; Lactones; Male; Multicenter Studies as Topic; Obesity; Orlistat; Prescription Fees; Randomized Controlled Trials as Topic; Reproducibility of Results

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

Topics: Animals; Anti-Obesity Agents; Body Weight; Clinical Trials as Topic; Humans; Lactones; Leptin; Obesity; Orlistat; Recombinant Proteins

Topics: Aged; Alopecia; Anti-Obesity Agents; Drug Prescriptions; Drug Therapy; Enzyme Inhibitors; Erectile Dysfunction; Female; Finasteride; Humans; Lactones; Male; Middle Aged; Nonprescription Drugs; Obesity; Orlistat; Phosphodiesterase Inhibitors; Piperazines; Psychotropic Drugs; Purines; Sildenafil Citrate; Sulfones

Topics: Anti-Obesity Agents; Body Mass Index; Female; Humans; Lactones; Male; Obesity; Orlistat; Patient Selection; Risk Assessment; Treatment Outcome

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

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

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

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

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Lactones; Obesity; Orlistat

Topics: Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat

Topics: Anti-Obesity Agents; Female; Humans; Lactones; Male; Obesity; Orlistat

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; Behavior Therapy; Dietary Fats; Enzyme Inhibitors; Humans; Lactones; Lipase; Obesity; Orlistat

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

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

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

Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Germany; Humans; Lactones; Obesity; Orlistat; Treatment Outcome

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

Treatments for obesity are disappointing. None has yet shown an effect on morbidity and mortality. Nondrug treatments are poorly assessed. Stable long-term weight loss necessitates long-term management. Orlistat (Xenical, Hoffman-La Roche), a gastrointestinal lipase inhibitor, is indicated, in combination with a low-calorie diet, for management of obesity. The assessment file is bulky and methodologically sound, at least in terms of the weight loss end point. During medium-term trials (12 to 24 months), orlistat administered at a dose of 120 mg three times daily and combined with dietary intervention had a moderate positive effect on body weight (-3.5 kg on average). No longer-term trials have been done. It is unknown whether this drug affects morbidity and mortality linked to obesity. In clinical trials, patients treated with orlistat had an increased frequency of breast cancer. This potential risk is currently being assessed in a specific trial. Gastrointestinal adverse effects are frequent. Treatment is costly.

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Decision Making; Humans; Lactones; Obesity; Orlistat; Research Design; Treatment Outcome

Orlistat (Xenical), whose original mechanism of action consists of the selective inhibition of gastrointestinal lipases, has been recently commercialized for the treatment of obesity. Despite its recent launch and when compared to common anorectic agents, it has been much better evaluated in long-term trials carried out according to the rules of Good Clinical Practice. We will summarize the four recently published randomized, placebo-controlled, double-blind clinical trials lasting up to 1 to 2 years and evaluating the effects of orlistat 3 x 120 mg/day in obese patients (BMI > or = 28 kg/m2).

Topics: Clinical Trials as Topic; Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Research Design; Treatment Outcome

Topics: Anti-Obesity Agents; Bias; Breast Neoplasms; Dietary Fats; Female; Humans; Lactones; Obesity; Orlistat; Treatment Outcome

We detected markedly decreased cyclosporin blood levels in a heart-transplanted patient after the gastrointestinal lipase inhibitor orlistat was accidentally added to the treatment program to control for his obesity. Therefore, we determined cyclosporin plasma concentration time kinetics with and without orlistat reexposition in this patient.. Plasma concentration time kinetics of whole blood cyclosporin levels in an obese heart-transplant patient were measured using a standard monoclonal fluorescence polarisation immunoassay. Results were obtained in hourly intervals up to 12 h without and with co-therapy of 3 x 120 mg orlistat (Xenical, Roche Ltd., Switzerland). The orlistat re-exposition was started the day before taking blood samples.. Cyclosporin trough levels (98 ng/ml vs 52 ng/ml), maximum concentrations (532 ng/ml vs 74 ng/ml) and the area under the blood drug concentration-time curve (2832 ng h ml-1 vs 700 ng h ml-1) were greatly reduced with orlistat.. Orlistat markedly decreased blood cyclosporin concentrations, possibly due to an interference with its absorption in the small intestine. To avoid potential dangerous under-immunosuppression, orlistat should not be used in patients taking cyclosporin.

Topics: Anti-Obesity Agents; Area Under Curve; Cyclosporine; Drug Interactions; Enzyme Inhibitors; Heart Transplantation; Humans; Immunosuppressive Agents; Lactones; Lipase; Male; Obesity; Orlistat

Topics: Anti-Obesity Agents; Clinical Medicine; Enzyme Inhibitors; Humans; Lactones; Obesity; Orlistat; Periodicals as Topic; Publishing; Spain; Time Factors

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

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

Topics: Anti-Obesity Agents; Humans; Lactones; Magnoliopsida; Obesity; Orlistat; Phytotherapy

Topics: Anti-Obesity Agents; Female; Humans; Lactones; Male; Obesity; Orlistat

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

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

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: Humans; Lactones; Legislation, Drug; Lipase; Obesity; Orlistat; United Kingdom

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

Topics: Body Mass Index; Clinical Trials as Topic; Disease Management; Enzyme Inhibitors; Female; Humans; Lactones; Life Style; Lipase; Male; Obesity; Orlistat; Practice Guidelines as Topic; State Medicine; United Kingdom

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

In summary, THL is a potent inhibitor of pancreatic lipase, which is both selective and irreversible in its action in vitro. It is also likely that THL inhibits pancreatic lipase in vivo, since its acute administration to mice and squirrel monkeys suppresses absorption of dietary triglycerides, without an apparent alteration in the absorption of fatty acids. The marked loss in body weight and carcass fat of DIO rats with subchronic administration of THL strongly suggests that inhibition of pancreatic lipase is a feasible strategy for the treatment of obesity. Whether obese humans will overeat in response to a reduction in body energy stores is not known. However, it is probable that compliance to a therapy which maintains the present level of food intake while inducing excretion of dietary fat, will be greater than a reducing diet alone or conjunction with the currently available antiobesity drugs.

Topics: Animals; Dietary Fats; Eating; Intestinal Absorption; Lactones; Lipase; Macaca mulatta; Mice; Obesity; Orlistat; Pancreas; Rats; Rats, Inbred Strains