orlistat and Hypertension

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

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

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

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

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

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

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

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

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

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

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

Topics: Age Factors; Androgens; Dyslipidemias; Humans; Hypertension; Hypolipidemic Agents; Insulin Resistance; Kidney Failure, Chronic; Lactones; Metabolic Syndrome; Orlistat; Progesterone-Binding Globulin; Testosterone; Tumor Necrosis Factor-alpha; Tunica Intima

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

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

The 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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Orlistat, a lipase inhibitor, reduces dietary fat absorption, and thus could potentially alter the absorption of some concomitantly administered drugs, such as the nifedipine gastrointestinal therapeutic system (GITS). To assess the effect of orlistat on the bioavailability of nifedipine GITS, a third party-blind, placebo-controlled, randomized, two-way crossover study was performed in 18 healthy volunteers. Each participant received single 60-mg oral doses of nifedipine GITS (Procardia XL; Pfizer Labs, New York, NY) on the fourth day of treatment with 120 mg of orlistat or placebo three times a day for 6 days. The two treatments were separated by a washout period of at least 1 week. Serial blood samples were collected before and at appropriate intervals after each nifedipine dose to determine plasma concentrations of nifedipine. The 90% confidence intervals for the ratio of geometric least-square means for maximum concentration (C(max)) and area under the concentration-time curve (AUCo-t) and for the difference of arithmetic least-square means for time to maximum concentration (t(max)) indicate that the bioavailability of nifedipine was not altered by treatment with orlistat. Therapeutic doses of 120 mg of orlistat three times daily do not significantly alter the bioavailability of a single 60-mg oral dose of nifedipine GITS in healthy volunteers.

Topics: Administration, Oral; Adult; Analysis of Variance; Biological Availability; Calcium Channel Blockers; Cross-Over Studies; Delayed-Action Preparations; Drug Interactions; Enzyme Inhibitors; Female; Humans; Hypertension; Lactones; Male; Middle Aged; Nifedipine; Orlistat

To study the influence of the lipase inhibitor orlistat on the pharmacokinetics of the antihypertensive drugs atenolol, furosemide, captopril and nifedipine.. Four open-label, crossover studies were performed on six to eight healthy male volunteers. Orlistat was given in doses of 50 mg 3 times daily mid-meal for 7 (nifedipine and captopril) or 8 days (atenolol and furosemide). The four antihypertensive drugs (atenolol 100-mg tablet, furosemide 40-mg tablet, captopril 50-mg tablet and nifedipine 20-mg slow-release tablet) were administered in single doses twice, once before and once together, with orlistat at the end of the orlistat treatment period.. The plasma concentration time profiles and the pharmacokinetic parameters estimated for these drugs were in the expected range, except for furosemide, whose bioavailability was lower than reported in the literature. This was probably due to the fact that furosemide was given during a meal. There were minor, but statistically significant, differences in one of the pharmacokinetic parameters of furosemide and nifedipine (no difference for captopril and atenolol) when these drugs were given alone and in combination with orlistat: the half-life of furosemide was slightly longer, the time to peak plasma concentrations of nifedipine was slightly longer. None of these are considered to be clinically significant changes.. The lipase inhibitor orlistat given 50 mg 3 times daily does not alter the pharmacokinetics of atenolol, furosemide, nifedipine and captopril to a clinically significant extent.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Captopril; Chromatography, High Pressure Liquid; Cross-Over Studies; Diuretics; Drug Therapy, Combination; Enzyme Inhibitors; Female; Furosemide; Humans; Hypertension; Lactones; Male; Nifedipine; Orlistat

Activation of G protein-coupled receptors (GPCRs) can induce vasoconstriction via calcium signal-mediated and Rho-dependent pathways. Earlier reports have shown that diacylglycerol produced during calcium signal generation can be converted to an endocannabinoid, 2-arachidonoylglycerol (2-AG). Our aim was to provide evidence that GPCR signaling-induced 2-AG production and activation of vascular type1 cannabinoid receptors (CB1R) is capable of reducing agonist-induced vasoconstriction and hypertension. Rat and mouse aortic rings were examined by myography. Vascular expression of CB1R was demonstrated with immunohistochemistry. Rat aortic vascular smooth muscle cells (VSMCs) were cultured for calcium measurements and 2-AG-determination. Inhibition or genetic loss of CB1Rs enhanced vasoconstriction induced by angiotensin II (AngII) or phenylephrine (Phe), but not by prostaglandin(PG)F2α. AngII-induced vasoconstriction was augmented by inhibition of diacylglycerol lipase (tetrahydrolipstatin) and was attenuated by inhibition of monoacylglycerol lipase (JZL184) suggesting a functionally relevant role for endogenously produced 2-AG. In Gαq/11-deficient mice vasoconstriction was absent to AngII or Phe, which activate Gq/11-coupled receptors, but was maintained in response to PGF2α. In VSMCs, AngII-stimulated 2-AG-formation was inhibited by tetrahydrolipstatin and potentiated by JZL184. CB1R inhibition increased the sustained phase of AngII-induced calcium signal. Pharmacological or genetic loss of CB1R function augmented AngII-induced blood pressure rise in mice. These data demonstrate that vasoconstrictor effect of GPCR agonists is attenuated via Gq/11-mediated vascular endocannabinoid formation. Agonist-induced endocannabinoid-mediated CB1R activation is a significant physiological modulator of vascular tone. Thus, the selective modulation of GPCR signaling-induced endocannabinoid release has a therapeutic potential in case of increased vascular tone and hypertension.

Topics: Angiotensin II; Animals; Aorta; Arachidonic Acids; Benzodioxoles; Calcium; Calcium Signaling; Dinoprost; Endocannabinoids; Gene Expression Regulation; Glycerides; GTP-Binding Protein alpha Subunits, Gq-G11; Hypertension; Lactones; Lipoprotein Lipase; Male; Mice; Mice, Knockout; Monoacylglycerol Lipases; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Orlistat; Phenylephrine; Piperidines; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Tissue Culture Techniques; Vasoconstriction

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

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

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

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

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

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

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

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

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

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

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

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

Obesity is 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

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

Topics: Anti-Obesity Agents; Blood Pressure; Humans; Hypertension; Lactones; Orlistat

Topics: Adult; Anti-Obesity Agents; Antihypertensive Agents; Blood Pressure; Drug Interactions; Female; Humans; Hypertension; Lactones; Male; Orlistat

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

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