orlistat and Cardiovascular-Diseases

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

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

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

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

This review considers drug combinations and newer treatment strategies for patients with severe hypertriglyceridemia. Hypertriglyceridemia is associated with an atherogenic metabolic profile and in most studies with increased cardiovascular disease risk. Patients with severe hypertriglyceridemia also have increased incidence of pancreatitis. All types of severe hypertriglyceridemia are associated with a reduction in lipoprotein lipase activity. Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis. Fibrates are the first-line treatment in patients with severe hypertriglyceridemia. Omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia. Statins in high doses exhibit a significant hypotriglyceridemic activity. Drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients. In most patients with severe hypertriglyceridemia drug combinations are needed to maintain an acceptable triglyceride concentration. Gene therapy is under development for patients with known genetic abnormalities of triglyceride metabolism. Clinicians should be vigilant for the recognition and prompt treatment of patients with severe hypertriglyceridemia aimed to avoid the serious complication of pancreatitis and to reduce their cardiovascular risk.

Topics: Algorithms; Blood Component Removal; Cardiovascular Diseases; Diet, Fat-Restricted; Fatty Acids, Omega-3; Fibric Acids; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lactones; Life Style; Niacin; Orlistat; Practice Guidelines as Topic; Severity of Illness Index; Triglycerides

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Insulin resistance, and the compensatory hyperinsulinemia that results, has been linked to a host of defects including glucose intolerance, diabetes, hypertension, dyslipidemia, endothelial dysfunction, impaired fibrinolysis, and subclinical inflammation. Patients with this metabolic syndrome have a markedly increased risk for the development of atherothrombotic cardiovascular disease. The characteristic dyslipidemia of insulin resistance consists of elevated triglyceride and triglyceride-rich lipoprotein levels, low levels of high-density lipoprotein cholesterol, and increased concentrations of small, dense low-density lipoprotein cholesterol. Management of this dyslipidemia typically involves a dual approach. Lifestyle modification is an essential component of any successful treatment plan, but alone is usually insufficient to correct these lipoprotein abnormalities. Medications that diminish insulin resistance and directly alter lipoproteins are also necessary in the majority of cases. Combinations of therapeutic agents are often required to optimize attainment of treatment goals.

Topics: Cardiovascular Diseases; Enzyme Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Lactones; Life Style; Lipase; Metformin; Niacin; Orlistat; Risk Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Antihypertensive Agents; Atorvastatin; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Drug Therapy, Combination; Fenofibrate; Fibrinogen; Heptanoic Acids; Humans; Hypolipidemic Agents; Inflammation; Lactones; Leukocyte Count; Metabolic Syndrome; Metformin; Orlistat; Prospective Studies; Pyrroles; Treatment Outcome

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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