orlistat and Body-Weight

Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight.. To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS.. We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021.. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020.. Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool.. Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.

Topics: Acarbose; Body Weight; Female; Humans; Hypoglycemic Agents; Metformin; Orlistat; Pioglitazone; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Rosiglitazone

This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.. Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction.. For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.. Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.. This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.. In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.

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

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

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

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

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

To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C-reactive protein (CRP).. Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size.. Meta-analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: -13.24%, 95% CI: -20.69, -5.78, p = 0.001) and CRP (WMD: -11.52%, 95% CI: -16.55, -6.49, p < 0.001) following treatment with orlistat. In meta-regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values.. Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.

Topics: Adiponectin; Anti-Obesity Agents; Body Weight; C-Reactive Protein; Ghrelin; Humans; Lactones; Leptin; Metabolic Syndrome; Orlistat; Randomized Controlled Trials as Topic

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

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

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

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

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

Organochlorine compounds enter the body primarily as components of the diet. Their removal from the body is via excretion into the feces. There is evidence that many people are in a positive balance, with the rate of intake of organochlorines exceeding that of their excretion. A desirable nutritional approach to this problem would both reduce dietary intake and increase fecal excretion. Nonabsorbable dietary lipids reduce the absorption of dietary organochlorines and also increase the rate of their fecal excretion. Organochlorine compounds that are stored in the body enter the intestine both in bile and through a poorly understood nonbiliary mechanism. Part of the amount that enters the intestine is excreted, and part is reabsorbed in an enterohepatic circulation. There is evidence that an increase in excretion can be achieved by interference with the enterohepatic circulation of organochlorine compounds and their metabolites. Data from animals and humans show that the presence of nonabsorbed lipid in the intestine can increase the rate of excretion in a clinically significant manner.

Topics: Adipose Tissue; Animals; Body Weight; Caloric Restriction; Defecation; Dietary Fats; Enterohepatic Circulation; Hexachlorobenzene; Humans; Hydrocarbons, Chlorinated; Intestinal Absorption; Intestine, Small; Lactones; Lipid Metabolism; Orlistat

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  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

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

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

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

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

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

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

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

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

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

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

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

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

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

To 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

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

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

The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.

Topics: Adult; Appetite; Body Weight; Cholecystokinin; Dietary Fats; Double-Blind Method; Eating; Energy Metabolism; Enzyme Inhibitors; Feces; Female; Humans; Lactones; Lipase; Male; Orlistat

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

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

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 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

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

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

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

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

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

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

The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol > or = 6.2 mmol.l-1 and triglycerides < or = 5.0 mmol.l-1) not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg or orlistat or placebo for 8 weeks. Total and low-density lipoprotein cholesterol levels were reduced by 4% and 5% with 30 mg orlistat, by 7% and 8% with 90 mg orlistat, by 7% and 7% with 180 mg orlistat and by 11% and 10% with 360 mg orlistat compared to placebo. High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group. Triglyceride levels significantly increased in the placebo group but not in the drug groups. Body weight decreased by 1.2 kg with 360 mg orlistat, despite a weight maintenance diet. Decreases in vitamin E and D levels occurred, although both vitamins remained within the normal range. Adverse effects from the gastrointestinal tract were frequent, but led to discontinuation of therapy in only seven patients. Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients. Its potential place in therapy will await long-term studies. Vitamin supplementation should be considered during treatment.

Topics: Adult; Aged; Apolipoproteins; Body Weight; Cholesterol, VLDL; Diet, Fat-Restricted; Digestive System; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperlipidemias; Lactones; Lipase; Lipids; Lipoproteins; Male; Middle Aged; Orlistat; Triglycerides; Vitamins

<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

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

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 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

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 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

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

The purpose of the present research work was to formulate, evaluate, and optimize self-emulsifying orlistat tablet to enhance drug release followed by in vivo antiobesity activity in Wistar rats. Initially, the solubility of orlistat was determined in different natural oils, surfactant, and co-surfactants. Self-emulsifying drug delivery system (SEDDS) was prepared by using castor oil, Tween 80, and Capryol PGMC as components. Liquid SEDDS evaluated for globule size and emulsification time. A 3(2) full factorial design was utilized for the optimization purpose. Formulation variables such as quantity of oil (X1) and ratio of surfactant to co-surfactant (X2) were investigated for their effect on globule size and emulsification time. Optimized formulation with minimum globule size was freeze-dried which further compressed into the tablet. Finally, optimized formulation evaluated for the in vitro drug release study followed by weight losing potential in Wistar rats. Globule size and emulsification time for the optimized formulation were found to be 96.4 ± 8.5 nm and 26 ± 4 s, respectively. Fourier transform infra red spectroscopy (FTIR) studies indicated that there was no interaction between drug and excipients. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study revealed that there was the conversion of crystalline orlistat to the amorphous form. Orlistat release from the self-emulsifying tablet formulation was faster with higher weight reduction potential in Wistar rats than the marketed formulation. Increased in vitro drug release with considerable in vivo weight loss by self-emulsifying tablet suggests that the SEDDS could serve as potential formulation strategy for orlistat.

Topics: Administration, Oral; Animals; Biological Availability; Body Weight; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Liberation; Emulsions; Lactones; Male; Orlistat; Rats; Solubility; Surface-Active Agents; Tablets

The present study investigated inhibition of pancreatic lipase and metabolic effects of high caloric diet in rats. The Passiflora nitida hydroethanol leaf extract (PNE) was used in in vitro assays or administered to rats to study dyslipidemia. Inhibition of lipase in vitro was studied by a spectrophotometric assay using orlistat as the positive control. The effects of PNE on reduction of postprandial triglyceride were studied by oral fat-overloading in rats. Metabolic alterations were induced using the cafeteria diet and 4 weeks post-treatment with PNE or orlistat and blood samples were collected and biochemical analyses were performed. Liver and retroperitoneal fat tissues were obtained to analyze weight and steatosis. IC50 (lg/mL) values for pancreatic lipase inhibition were 21.2 ± 0.8 and 0.1 ± 0.01 for PNE and orlistat, respectively. Oral administration of lipid emulsion resulted in postprandial hypertriglyceridemia at 3 h postadministration and when rats were then administered PNE and orlistat there was decreased of triglyceride levels by 15 % compared to control. Although the energy consumption by the cafeteria diet had been higher, there was no significant weight gain observed in the study groups. The cafeteria diet resulted in a significant increase of weight in the retroperitoneal fat and hypertriglyceridemia levels that could be significantly reduced by PNE and orlistat treatment. We hypothesized that PNE administration prevented the hypertriglyceridemia in rats with a high caloric diet, possibly owing to reduction of lipid absorption and pancreatic lipase inhibition.

Topics: Adipose Tissue; Animals; Body Weight; Diet; Energy Intake; Enzyme Inhibitors; Hypertriglyceridemia; Lactones; Lipase; Lipids; Liver; Male; Orlistat; Passiflora; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Triglycerides

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

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

Investigation was conducted to understand the mechanism of action of diacylglycerol acyltransferase 1 (DGAT1) using small molecules DGAT1 inhibitors, compounds K and L.. Biochemical and stable-label tracer approaches were applied to interrogate the functional activities of compounds K and L on TG synthesis and changes of carbon flow. Energy homeostasis and gut peptide release upon DGAT1 inhibition was conducted in mouse and dog models.. Compounds K and L, dose-dependently inhibits post-prandial TG excursion in mouse and dog models. Weight loss studies in WT and Dgat1(-/-) mice, confirmed that the effects of compound K on body weight loss is mechanism-based. Compounds K and L altered incretin peptide release following oral fat challenge. Immunohistochemical studies with intestinal tissues demonstrate lack of detectable DGAT1 immunoreactivity in enteroendocrine cells. Furthermore, (13) C-fatty acid tracing studies indicate that compound K inhibition of DGAT1 increased the production of phosphatidyl choline (PC).. Treatment with DGAT1 inhibitors improves lipid metabolism and body weight. DGAT1 inhibition leads to enhanced PC production via alternative carbon channeling. Immunohistological studies suggest that DGAT1 inhibitor's effects on plasma gut peptide levels are likely via an indirect mechanism. Overall these data indicate a translational potential towards the clinic.

Topics: Animals; Body Composition; Body Weight; Chromatography, Liquid; Diacylglycerol O-Acyltransferase; Disease Models, Animal; Dogs; Enteroendocrine Cells; Feces; Gastrointestinal Tract; Ginsenosides; Hormones; HT29 Cells; Humans; Immunohistochemistry; Lactones; Male; Mice; Mice, Inbred C57BL; Orlistat; Postprandial Period; Tandem Mass Spectrometry; 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

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

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

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

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

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; 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

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

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

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

Treatment with phototherapy or with the lipase inhibitor orlistat decreases plasma unconjugated bilirubin (UCB) concentrations in hyperbilirubinemic Gunn rats. We investigated the mechanism(s) underlying the effects of orlistat, phototherapy, and combined treatment, using steady-state 3H-UCB kinetics. After three weeks of treatment with orlistat (200 mg/kg chow), phototherapy (19 microW/cm2/nm) or combined treatment, tracer 3H-UCB was administered IV to treated and untreated (control) Gunn rats. Plasma samples and feces were collected every 12h for 60h, and bile for 30 min at 60h. The following results were obtained: 1) each treatment decreased plasma bilirubin levels compared with controls: orlistat- 19%, phototherapy-32%, combined treatment-53%; 2) plasma bilirubin concentrations were strongly, negatively correlated with fractional bilirubin turnover; 3) orlistat treatment induced net transmucosal excretion of UCB into the intestinal lumen, whereas phototherapy increased biliary UCB excretion rate; 4) all treatments profoundly increased the enterohepatic circulation of UCB derivatives, indicating enhanced metabolism by intestinal bacteria. In conclusion, orlistat and phototherapy lower plasma bilirubin concentrations in Gunn rats by increasing (net) intestinal influx of UCB, either by transmucosal excretion (orlistat), or increased biliary secretion (phototherapy). The mechanism of phototherapy and orlistat treatment involves increasing the availability of UCB in the intestinal lumen for fecal excretion and for metabolism by intestinal bacteria.

Topics: Animals; Bile; Bilirubin; Body Weight; Combined Modality Therapy; Eating; Enzyme Inhibitors; Feces; Hyperbilirubinemia; Lactones; Lipase; Male; Orlistat; Phototherapy; Rats; Rats, Gunn; Tritium

The aim of this postmarketing surveillance (PMS) study was to investigate the effect of an orlistat therapy under the everyday conditions of our health care system.. 11 131 women and 4418 men from Germany [mean age 48 years, mean body mass index (BMI) 34.7 kg/m(2) and mean duration of obesity 13.7 years] were included. The patients were predominantly cared for by general practitioners. Four fifths of the patients reported having obesity-associated co-morbidities. All patients were advised to take orlistat 120 mg three times daily.. After a mean treatment duration of 7.1 months, both women and men lost 10.7% of their baseline weight (87% lost > 5% weight and 51% lost > 10% weight). All cardiovascular risk factors improved markedly, and the intake of concomitant medications was either reduced or discontinued. Compared with baseline, 65% of the patients assessed their general state of health to have improved. For more than 90% of their patients, physicians described the success of the treatment as satisfactory, and most patients (62%) were willing to continue with the treatment.. The results obtained in this naturalistic PMS study were comparable with the results of randomised and placebo-controlled studies, which were performed predominantly in special care centres. Therefore, without any risk of adversely affecting the quality of treatment provided, the treatment of obese patients with orlistat may be transferred to general practitioners.

Topics: Adult; Anti-Obesity Agents; Body Weight; Family Practice; Female; Humans; Lactones; Male; Middle Aged; Obesity, Morbid; Orlistat; Product Surveillance, Postmarketing

Unabsorbed fat and bile acids may react with calcium in the intestinal lumen, limiting the amount of free calcium binding with oxalate and thereby raising intestinal oxalate absorption leading to hyperoxaluria. The aim of the present study was to determine whether orlistat (Xenical), a gastrointestinal lipase inhibitor, might increase urinary oxalate in an experimental rat model.. Thirty-nine male adult Wistar rats were fed a standard diet alone (controls) or supplemented with either 2% sodium oxalate (NaOx) or 3.2 mL of soy oil, or with both (NaOx + soy oil) for 4 weeks (diet period). Orlistat (16 mg/day) was added to the diet from the 5th to the 8th week (diet + orlistat period). Urinary oxalate (uOx), calcium (uCa), magnesium (uMg), and citrate (uCit) were determined and the ion-activity product of calcium oxalate [AP (CaOx) index(rat)] was estimated.. Compared to baseline uOx significantly increased after diet + orlistat in controls (0.64 +/- 0.1 mg/24 hours vs. 0.56 +/-0.1 mg/24 hours), soy oil (0.80 +/- 0.3 mg/24 hours vs. 0.49 +/-0.2 mg/24 hours), and NaOx (2.48 +/- 0.8 mg/24 hours vs. 0.57 +/- 0.2 mg/24 hours), but the most marked increase occurred in NaOx + soy oil (3.87 +/- 0.7 mg/24 hours vs. 0.47 +/- 0.1 mg/24 hours). All groups except controls presented a significant reduction in uCa and uMg. Orlistat induced a significant increase in AP (CaOx) index(rat) compared, respectively, to baseline and to the diet period in NaOx (4.52 +/- 2.34 mg/24 hours vs. 0.94 +/- 0.86 and 1.53 +/- 0.93 mg/24 hours) and NaOx + soy oil (6.49 +/- 4.03 mg/24 hours vs. 0.54 +/- 0.17 and 1.76 +/- 1.32 mg/24 hours).. These data suggest that the use of lipase inhibitors, especially under a diet rich in oxalate alone or associated with fat, leads to a significant and marked increase in urinary oxalate and a slight reduction in uCa and uMg that, taken together, resulted in an increase in AP (CaOx) index(rat), elevating the risk of stone formation.

Topics: Animals; Body Weight; Calcium Oxalate; Dietary Fats; Enzyme Inhibitors; Feces; Kidney Calculi; Lactones; Lipase; Malabsorption Syndromes; Male; Orlistat; Rats; Rats, Wistar; Risk Factors

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

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

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

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

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

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.

Topics: Animals; Body Weight; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Eating; Energy Intake; Enzyme Inhibitors; Female; Food Preferences; Lactones; Lipase; Orlistat; Rats; Rats, Sprague-Dawley; Self Administration