title: Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. Weight loss in obese Mexican Americans treated for 1-year with orlistat and lifestyle modification Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Effect of orlistat added to diet (30% of calories from fat) on plasma lipids, glucose, and insulin in obese patients with hypercholesterolemia. Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients Cholesterol lowering effect of dietary weight loss and orlistat treatment – efficacy and limitations Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both an anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet. Lipoprotein(a) as a cardiovascular risk factor: current status Retrospective population‐based analysis of the dose‐response (fecal fat excretion) relationship of orlistat in normal and obese volunteers Effect of Orlistat on Weight Regain and Cardiovascular Risk Factors Following a Very-Low-Energy Diet in Abdominally Obese Patients Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilatation in obese women with previous gestational diabetes. Comparison of the effects of sibutramine and orlistat on obese, poorly-controlled type 2 diabetic patients. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss. The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial. Effect of Orlistat in obese patients with heart failure: a pilot study. Orlistat increases serum paraoxonase activity in obese patients. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Long-term persistence with orlistat and sibutramine in a population-based cohort Effect of orlistat on cardiovascular disease risk in obese adults Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1. Effects of orlistat on obesity-related diseases - a six-month randomized trial. Orlistat for obesity: benefits beyond weight loss. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor Orlistat as an adjunct therapy in type 2 obese diabetic patients treated with sulphonylurea: a Bangladesh experience. The effects of ezetimibe and orlistat, alone or in combination, on high-density lipoprotein (HDL) subclasses and HDL-associated enzyme activities in overweight and obese patients with hyperlipidaemia. Orlistat inhibits dietary cholesterol absorption. Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients. A randomized double-blind study comparing the efficacy and safety of orlistat versus placebo in obese patients with mild to moderate hypercholesterolemia. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome.
abstract: Objective 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 . Design A pragmatic r and omized , controlled trial . Setting Hypertension clinic of a university hospital . Patients Hypertensive patients aged 18–75 years with a body mass index greater than 25 kg/m2 . Interventions Orlistat 360 mg/day combined with a hypocaloric diet ( treatment group ) , or a calorie-restricted diet alone ( control group ) . Main outcome measures 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 . Results 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 . Conclusion 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 CONTEXT The prevalence of overweight and obesity in children and adolescents is increasing rapidly . In this population , behavioral therapy alone has had limited success in providing meaningful , sustained weight reduction , and pharmacological treatment has not been extensively studied . OBJECTIVE To determine the efficacy and safety of orlistat in weight management of adolescents . DESIGN , SETTING , AND PATIENTS Multicenter , 54-week ( August 2000-October 2002 ) , r and omized , double-blind study of 539 obese adolescents ( aged 12 - 16 years ; body mass index [ BMI ] > or=2 units above the 95th percentile ) at 32 centers in the United States and Canada . INTERVENTIONS A 120-mg dose of orlistat ( n = 357 ) or placebo ( n = 182 ) 3 times daily for 1 year , plus a mildly hypocaloric diet ( 30 % fat calories ) , exercise , and behavioral therapy . MAIN OUTCOME MEASURES Change in BMI ; secondary measures included changes in waist and hip circumference , weight loss , lipid measurements , and glucose and insulin responses to oral glucose challenge . RESULTS There was a decrease in BMI in both treatment groups up to week 12 , thereafter stabilizing with orlistat but increasing beyond baseline with placebo . At the end of the study , BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo ( P = .001 ) . Compared with 15.7 % of the placebo group , 26.5 % of participants taking orlistat had a 5 % or higher decrease in BMI ( P = .005 ) ; 4.5 % and 13.3 % , respectively , had a 10 % or higher decrease in BMI ( P = .002 ) . At study end , weight had increased 0.53 kg with orlistat and 3.14 kg with placebo ( P<.001 ) . Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass . Waist circumference decreased in the orlistat group but increased in the placebo group ( -1.33 cm vs + 0.12 cm ; P<.05 ) . Generally mild to moderate gastrointestinal tract adverse events occurred in 9 % to 50 % of the orlistat group and in 1 % to 13 % of the placebo group . CONCLUSIONS In combination with diet , exercise , and behavioral modification , orlistat statistically significantly improved weight management in obese adolescents compared with placebo . The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group OBJECTIVE : To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women . SUBJECTS : Mexican-American women ( N=108 ) , aged 21–65 y , with a body mass index ( BMI ) ≥27 kg/m2 were r and omized 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 ) . DESIGN : A r and omized , 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 ( ≤30 % of total daily calories ) diet , and moderate physical activity ( ≥150 min/week).MEASUREMENT : Primary outcomes included changes in body weight ( kg ) , BMI , waist circumference , blood pressure , glucose , and lipids . RESULTS : 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 × treatment interaction ( Wilks ' λ=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 . CONCLUSIONS : This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women , a population with substantial risk for obesity BACKGROUND Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment . OBJECTIVE This multicenter , double-blind , placebo-controlled study was design ed to test the hypothesis that orlistat , a gastrointestinal lipase inhibitor , is significantly more effective than a placebo in preventing weight regain . DESIGN 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 r and omly 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 . RESULTS 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 ) . CONCLUSION The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors The objective of this study was to quantify the effectiveness of orlistat plus a reduced calorie diet on decreasing cardiovascular disease risk in obese individuals with elevated low-density lipoprotein ( LDL ) cholesterol concentrations , and to compare the beneficial effects in patients with hypercholesterolemia only ( type IIA ) with those in subjects with combined dyslipidemia ( type IIB ) . Hypercholesterolemic patients treated with orlistat lost more weight ( mean + /- SEM 9.9 + /- 0.4 vs 6.1 + /- 0.5 kg , p = 0.0001 ) and had greater decreases in plasma cholesterol ( p = 0.0001 ) , LDL cholesterol ( p = 0.0001 ) , triglycerides ( p = 0.06 ) , glucose ( p = 0.07 ) , and insulin ( p = 0.02 ) concentrations compared with the diet-only treated patients . The greater degree of weight loss in orlistat-treated subjects was similar irrespective of the form of dyslipidemia , and plasma total and LDL cholesterol and insulin levels decreased to a significantly greater degree ( p < 0.05 ) in those patients who received orlistat and who had either type IIA and IIB dyslipidemia . However , triglyceride and insulin concentrations decreased and high-density lipoprotein ( HDL ) cholesterol increased to a significantly greater degree following orlistat-assisted weight loss in patients with type IIB compared with type IIA subjects , which was associated with a significantly greater decrease in the ratio of LDL/HDL cholesterol . Thus , weight loss in response to a reduced calorie diet in obese hypercholesterolemic patients was associated with a significant decrease in plasma LDL cholesterol levels . The beneficial metabolic effects of weight loss were accentuated in response to orlistat administration , and the improvement was greatest in patients with combined dyslipidemia ( type IIB ) Aim : 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 Background : Orlistat reduces energy uptake by the impairment of fat digestion and some evidence indicates it also lowers plasma cholesterol OBJECTIVE The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a st and ardized diet , comparing the action of orlistat , fluvastatin , orlistat with fluvastatin , and placebo on anthropometric measurements , blood pressure ( BP ) , and lipid profile . METHODS This was a 1-year , r and omized , double-blind , placebo-controlled trial . The patients were prescribed a controlled-energy diet and were r and omly allocated to receive placebo , orlistat 120 mg TID ( O group ) , fluvastatin 80 mg/d ( F group ) , or olistat 120 mg TID with fluvastatin 80 mg/d ( OF group ) . Clinical measurements ( body weight , body mass index [ BMI ] , waist circumference , and BP ) and lipid profile assessment ( total cholesterol [ TC ] , low-density lipoprotein cholesterol [ LDL-C ] , high-density lipoprotein cholesterol [ HDL-C ] , and triglycerides [ TGs ] ) were performed at baseline and after 6 months and 1 year of treatment . RESULTS The study included 99 obese patients with hypercholesterolemia ( 48 men and 51 women ; mean [ SD ] age , 51 [ 9 ] years ) . There were no significant differences between groups in baseline demographic , BP , or plasma lipid values . Three patients dropped out ( 2 women in the O group and 1 man in the OF group ) due to adverse events related to orlistat treatment , including gastrointestinal events ( oily spotting and fecal urgency ) .  Ninety-six patients completed the study . There were significant differences from baseline ( mean [ SD ] ) in BMI , waist circumference reduction ( WCR ) , and body weight loss ( BWL ) at 6 months in the OF group ( 29.9 [ 1.1 ] kg/m(2 ) , 2.7 [ 0.8 ] cm , and 7.4 [ 0.9 ] kg , respectively ; all P < 0.05 ) , and BMI , WCR , and BWL at 1 year in the O group ( 29.0 [ 1.0 ] kg/m(2 ) , 3.0 [ 1.0 ] cm , and 8.6 [ 1.0 ] kg , respectively ; all P < 0.02 ) , the F group ( 29.3 [ 1.6 ] kg/m(2 ) , 2.4 [ 1.0 ] cm , and 8/0 [ 1.0 ] kg , respectively ; all P < 0.05 ) , and the OF group ( 28.4 [ 0.6 ] kg/m(2 ) , 4.0 [ 0.6 ] cm , and 11.4 [ 1.0 ] kg , respectively ; all P < 0.01 ) . Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups ( all P < 0.05 ) and the OF group ( both P < 0.01 ) . At 6 months , there were significant reductions from baseline in TC and LDL-C in the F group ( both P < 0.05 ) and in TC , LDL-C , and TGs in the OF group ( P < 0.02 , P < 0.02 , and P < 0.05 , respectively ) , as well as a significant increase in HDL-C in the OF group ( P < 0.02 ) . At 1 year , there were significant reduction from baseline in TC in the O , F , and OF groups ( P < 0.05 and P < 0.01 , respectively ) , LDL-C ( P < 0.05 , P < 0.02 , and P < 0.01 , respectively ) , and TGs ( P < 0.02 , P < 0.05 , and P < 0.02 , respectively ) . Also at 1 year , HDL-C was significantly higher than baseline in the F and OF groups ( P < 0.02 and P < 0.01 , respectively ) . CONCLUSION Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD  by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction Orlistat , an inhibitor of gastrointestinal lipases , limits the absorption of ingested fat and could become a potential treatment for obesity . This analysis was performed to eluci date the relationship between orlistat dose and intensity of inhibition of dietary fat absorption ( assessed by measuring fecal fat excretion ) . In 11 phase I double‐blind , placebo‐controlled , parallel‐group r and omized studies , a total of 171 subjects received oral daily doses that ranged from 30 to 1200 mg orlistat or matching placebo three times a day for 9 to 10 days . The results of the daily mean fecal fat excretion percentage ( relative to ingested fat ) were correlated to the orlistat daily dose . A simple maximum‐effect model that included a basal value was used to fit the dose‐response relationship for all evaluable subjects . The mean maximum percentage of ingested fat excreted in the feces was approximately 32 % during orlistat administration compared with 5 % during placebo administration . The orlistat daily dose that produced 50 % of the maximum effect was 98 mg/day . The model‐fitting suggests the existence of a steep portion of the dose‐response curve up to approximately 400 mg/day , with a subsequent tendency to plateau at higher doses . Such an analysis was instrumental in identifying appropriate doses to be used in therapeutic trials for weight loss in obese patients OBJECTIVE —To investigate the efficacy of orlistat on the maintenance of weight loss over 3 years following a major weight loss induced by very-low-energy diet ( VLED ) in obese patients with metabolic risk factors such as dyslipidemia , impaired fasting glucose , and diet-treated type 2 diabetes . RESEARCH DESIGN AND METHODS —Initially , weight loss was induced by an 8-week VLED ( 600–800 kcal/day ) in 383 patients with a mean BMI of 37.5 kg/m2 ( range 30.0–45.2 ) . Those who lost ≥5 % of their body weight ( 309 of 383 patients ) were then r and omized to receive lifestyle counseling for 3 years together with either orlistat 120 mg t.i.d . or matching placebo capsules . Primary end points were the maintenance of ≥5 % weight loss after 3 years . Additionally , differences in the development of type 2 diabetes between orlistat and placebo were analyzed . RESULTS —The VLED induced a mean weight loss of 14.4 ± 2 .. 0 kg among the subsequently r and omized patients . The mean weight gain after 3 years was lower with orlistat than with placebo ( 4.6 ± 8.6 vs. 7.0 ± 7.1 kg ; P < 0.02 ) . The number of participants who achieved ≥5 % weight loss also favored orlistat ( 67 vs. 56 % ; P = 0.037 ) . Waist circumference was significantly more reduced in the orlistat group ( P < 0.05 ) , but no other differences in the risk factors were observed between the two groups . The incidences of new cases of type 2 diabetes were significantly reduced in the orlistat group ( 8 cases out of 153 subjects ) versus placebo ( 17 cases out of 156 subjects ) ( P = 0.041 ) . CONCLUSIONS —The addition of orlistat to lifestyle intervention was associated with maintenance of an extra 2.4 kg weight loss after VLED for up to 3 years in obese subjects . The combination of orlistat and lifestyle intervention was associated with a reduced occurrence of type 2 diabetes OBJECTIVE The purpose of this study was to assess the effect of orlistat , a gastrointestinal lipase inhibitor , on body weight , glycemic control , and cardiovascular risk factors in metformin-treated type 2 diabetic patients . RESEARCH DESIGN AND METHODS A 1-year multicenter , r and omized , double-blind , placebo-controlled trial of 120 mg  orlistat t.i.d . ( n = 249 ) or placebo ( n = 254 )  combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes . RESULTS After 1 year of treatment , mean ( + /-SE ) weight loss was greater in the orlistat than in the placebo group ( -4.6 + /- 0.3 % vs. -1.7 + /- 0.3 % of baseline wt , P < 0.001 ) . Orlistat treatment caused a greater improvement in glycemic control than placebo , as evidence d by a greater reduction in serum HbA(1c ) , adjusted for changes in metformin and sulfonylurea therapy ( -0.90 + /- 0.08 vs. -0.61 + /- 0.08 , P = 0.014 ) ; a greater proportion of patients achieving decreases in HbA(1c ) of > or = 0.5 and > or = 1.0 % ( both P < 0.01 ) ; and a greater reduction in fasting serum glucose ( -2.0 + /- 0.2 vs. -0.7 + /- 0.2 mmol/l , P = 0.001 ) . Compared with the placebo group , patients treated with orlistat also had greater decreases in total cholesterol , LDL cholesterol , and systolic blood pressure ( all P < 0.05 ) . Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo ( 83 vs. 62 % , P < 0.05 ) , more subjects in the placebo group withdrew prematurely from the study than in the orlistat group ( 44 vs. 35 % , P < 0.05 ) . CONCLUSIONS Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control , serum lipid levels , and blood pressure in obese patients with type 2 diabetes who are being treated with metformin OBJECTIVE Effects of weight loss on vascular function are unknown . We compared , in the face of similar weight loss over 3 - 6 months , effects of orlistat ( 120 mg t.i.d . , n = 23 ) and placebo ( n = 24 ) on in vivo endothelial function in a high-risk group of obese ( BMI 32.1 + /- 0.4 kg/m(2 ) ) premenopausal nondiabetic women with a history of gestational diabetes . RESEARCH DESIGN AND METHODS Forearm blood flow responses to intra-arterial infusions of acetylcholine ( ACh ) and sodium nitroprusside ( SNP ) , body composition , and serum lipids were determined before and after weight loss . RESULTS Weight loss averaged 7.3 + /- 0.2 kg ( 8.3 + /- 0.1 % ) and 7.4 + /- 0.2 kg ( 8.2 + /- 0.1 % ) of initial body weight in the orlistat and placebo groups , respectively . Forearm and body compositions changed similarly in both groups . Responses to ACh increased by 41 % to the low dose ( 5.9 + /- 0.6 vs. 8.3 + /- 0.3 for flow in the experimental/control arm , P < 0.01 ) and by 33 % to the high dose ( 7.6 + /- 0.8 vs. 10.1 + /- 0.6 , P < 0.001 ) in the orlistat group , but they remained unchanged in the placebo group . The blood flow responses to SNP did not differ significantly between the groups . LDL cholesterol decreased significantly in the orlistat group from 3.5 + /- 0.2 to 3.0 + /- 0.1 mmol/l ( P < 0.01 ) but remained unchanged in the placebo group . Within the orlistat group , the decrease in LDL cholesterol correlated significantly with the improvement in the blood flow response to ACh ( r = -0.44 , P < 0.05 ) . CONCLUSIONS Orlistat but not moderate ( 8 % ) weight loss per se improves endothelial function in women with previous gestational diabetes . This improvement is associated with a lowering of LDL cholesterol by orlistat BACKGROUND We assessed and directly compared weight loss effects of sibutramine and orlistat treatment in a group of obese , poorly-controlled type 2 diabetic patients . METHODS This study recruited 34 diabetic subjects [ glycohemoglobin ( HbA1c ) > 8 % ] with a body mass index of at least 27 kg/m2 . A 36-week , three-phase , prospect i ve , r and omized , cross-over comparative study was conducted . In phase 1 , 34 patients were r and omly divided into two groups . One group received sibutramine for 3 months , then completed a 3 month wash-out period and , finally , shifted to orlistat for another 3 months . The second group followed the same procedure but received orlistat first and then sibutramine . The efficacy measures were rate of weight reduction , glycemic control , insulin sensitivity and cardiovascular risk factors , including waist circumference , lipid profiles and blood pressure . RESULTS The sibutramine-treated group achieved 2.0 kg ( 2.5 % ) weight loss with observable but not statistically significant changes in insulin sensitivity , glycemic control , and cardiovascular risk factors . There were no significant changes in systolic or diastolic blood pressure . The weight reduction in the orlistat-treated group was only 0.8 kg ( 0.9 % ) , which was significantly less than that of the sibutramine group . There were significant differences in total cholesterol , low density lipoprotein cholesterol and HbA1C . Direct comparative analysis revealed no significant differences between these two groups . CONCLUSION This study indicates that sibutramine treatment produced greater reduction in weight than orlistat in obese , poorly-controlled type 2 diabetic patients . However , no significant differences in waist circumference , and lipid or glucose levels were found between the two groups BACKGROUND Two potent weight loss therapies , a low-carbohydrate , ketogenic diet ( LCKD ) and orlistat therapy combined with a low-fat diet ( O + LFD ) , are available to the public but , to our knowledge , have never been compared . METHODS Overweight or obese out patients ( n = 146 ) from the Department of Veterans Affairs primary care clinics in Durham , North Carolina , were r and omized to either LCKD instruction ( initially , < 20 g of carbohydrate daily ) or orlistat therapy , 120 mg orally 3 times daily , plus low-fat diet instruction ( < 30 % energy from fat , 500 - 1000 kcal/d deficit ) delivered at group meetings over 48 weeks . Main outcome measures were body weight , blood pressure , fasting serum lipid , and glycemic parameters . RESULTS The mean age was 52 years and mean body mass index was 39.3 ( calculated as weight in kilograms divided by height in meters squared ) ; 72 % were men , 55 % were black , and 32 % had type 2 diabetes mellitus . Of the study participants , 57 of the LCKD group ( 79 % ) and 65 of the O + LFD group ( 88 % ) completed measurements at 48 weeks . Weight loss was similar for the LCKD ( expected mean change , -9.5 % ) and the O + LFD ( -8.5 % ) ( P = .60 for comparison ) groups . The LCKD had a more beneficial impact than O + LFD on systolic ( -5.9 vs 1.5 mm Hg ) and diastolic ( -4.5 vs 0.4 mm Hg ) blood pressures ( P < .001 for both comparisons ) . High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups . Low-density lipoprotein cholesterol levels improved within the O + LFD group only , whereas glucose , insulin , and hemoglobin A(1c ) levels improved within the LCKD group only ; comparisons between groups , however , were not statistically significant . CONCLUSION In a sample of medical out patients , an LCKD led to similar improvements as O + LFD for weight , serum lipid , and glycemic parameters and was more effective for lowering blood pressure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108524 The effect of orlistat , a nonabsorbed inhibitor of gastric and pancreatic lipases , was examined in patients with primary hyperlipidaemia ( serum cholesterol ≥6.2 mmol·l−1 and triglycerides ≤5.0 mmol·l−1 ) not responsive to dietary change alone . In a multicentre , r and omised , double-blind study , 103 men and 70 women received 30 , 90 , 180 , or 360 mg of orlistat or placebo for 8 weeks . Total and low-density lipoprotein cholesterol levels were reduced by 4 % and 5 % with 30 mg orlistat , by 7 % and 8 % with 90 mg orlistat , by 7 % and 7 % with 180 mg orlistat and by 11 % and 10 % with 360 mg orlistat  compared to placebo . High density lipoprotein cholesterol levels significantly decreased in the 360 mg  orlistat group . Triglyceride levels significantly increased in the placebo group but not in the drug groups . Body weight decreased by 1.2 kg with 360 mg orlistat , despite a weight maintenance diet . Decreases in vitamin E and D levels occurred , although both vitamins remained within the normal range . Adverse effects from the gastrointestinal tract were frequent , but led to discontinuation of therapy in only seven patients . Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients . Its potential place in therapy will await long-term studies . Vitamin supplementation should be considered during treatment This study describes the changes in risk factors for coronary heart disease in obese persons with syndrome X after orlistat-assisted weight loss . Data were available for 1,700 patients who completed 52 weeks of weight loss ; 128 were defined as having syndrome X by being in the quintile with the highest plasma triglyceride levels ( > 2.2 mM/L ) and the lowest high-density lipoprotein cholesterol ( HDL , < 1.0 mM/L ) concentrations . Initial characteristics of those with syndrome X were similar to the 119 subjects ( non-syndrome X ) in the lowest quintile of plasma triglyceride ( < 0.975 mM/L ) and highest quintile of HDL cholesterol ( > 1.5 mM/L ) . Subjects were placed on a calorie-restricted diet , and r and omized to receive orlistat or placebo . Initial values were higher in those with syndrome X for diastolic blood pressure ( p = 0.03 ) , plasma insulin ( p = 0.0001 ) , triglyceride ( p = 0.0001 ) concentrations , and ratio of low-density lipoprotein cholesterol to HDL cholesterol ( p = 0.0001 ) , and were lower for HDL cholesterol ( p = 0.001 ) concentrations . Weight loss was greater in both groups of orlistat-treated patients ( p = 0.026 ) ; in those with syndrome X , it was associated with a significant reduction in plasma insulin ( p = 0.019 ) and triglyceride ( p = 0.0001 ) concentrations , an increase in HDL cholesterol concentration , and a decrease in low-density lipoprotein/HDL cholesterol ratio ( p = 0.0001 ) . There were no significant changes in plasma insulin , triglycerides , or HDL cholesterol concentration in the non-syndrome X group . In conclusion , weight loss attenuates coronary heart disease risk factors in obese persons with syndrome X , and the risk factor reduction is enhanced with administration of orlistat OBJECTIVE It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity . A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated . We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight , and thus the incidence of type 2 diabetes , in obese patients . RESEARCH DESIGN AND METHODS In a 4-year , double-blind , prospect i ve study , we r and omized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo , three times daily . Participants had a BMI > /=30 kg/m2 and normal ( 79 % ) or impaired ( 21 % ) glucose tolerance ( IGT ) . Primary endpoints were time to onset of type 2 diabetes and change in body weight . Analyses were by intention to treat . RESULTS Of orlistat-treated patients , 52 % completed treatment compared with 34 % of placebo recipients ( P < 0.0001 ) . After 4 years ' treatment , the cumulative incidence of diabetes was 9.0 % with placebo and 6.2 % with orlistat , corresponding to a risk reduction of 37.3 % ( P = 0.0032 ) . Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT . Mean weight loss after 4 years was significantly greater with orlistat ( 5.8 vs. 3.0 kg with placebo ; P < 0.001 ) and similar between orlistat recipients with impaired ( 5.7 kg ) or normal glucose tolerance ( NGT ) ( 5.8 kg ) at baseline . A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group ( 3.6 vs. 1.4 kg ; P < 0.001 ) . CONCLUSIONS Compared with lifestyle changes alone , orlistat plus lifestyle changes result ed in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinical ly representative obese population . Difference in diabetes incidence was detectable only in the IGT subgroup ; weight loss was similar in subjects with IGT or NGT [ correction ] OBJECTIVE To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk . DESIGN After screening , patients entered a two-week single-blind placebo lead-in period , during which they followed a mildly hypocaloric diet , before being r and omized to double-blind treatment with either orlistat 120 mg or placebo three times daily , in conjunction with dietary intervention for 1 years . SETTING The study was conducted at 33 primary care centres in Sweden . SUBJECTS 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 r and omized to orlistat ( n = 190 ) or placebo ( n = 186 ) . MAIN OUTCOME MEASURES Change in body weight , waist and hip circumferences , blood pressure , serum lipid profile , fasting glucose and HbA1c . RESULTS 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 . CONCLUSIONS 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 OBJECTIVE To determine the effect of orlistat , a new lipase inhibitor , on long-term weight loss , to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment , and to assess the effects of orlistat on obesity-related risk factors . RESEARCH METHODS AND PROCEDURES This was a 2-year , multicenter , r and omized , double-blind , placebo-controlled study . Obese patients ( body mass index 28 to 43 kg/m2 ) were r and omized to placebo or orlistat ( 60 or 120 mg ) three times a day , combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain . Changes in body weight , lipid profile , glycemic control , blood pressure , quality of life , safety , and tolerability were measured . RESULTS  Orlistat-treated patients  lost significantly more weight ( p<0.001 ) than placebo-treated patients after Year 1 ( 6.6 % , 8.6 % , and 9.7 % for the placebo , and orlistat 60 mg and 120 mg groups , respectively ) . During the second year , orlistat therapy produced less weight regain than placebo ( p = 0.005 for orlistat 60 mg ; p<0.001 for orlistat 120 mg ) . Several obesity-related risk factors improved significantly more with orlistat treatment than with placebo . Orlistat was generally well tolerated and only 6 % of  orlistat-treated patients withdrew because of adverse events . Orlistat leads to predictable gastrointestinal effects related to its mode of action , which were generally mild , transient , and self-limiting and usually occurred early during treatment . DISCUSSION Orlistat administered for 2 years promotes weight loss and minimizes weight regain . Additionally , orlistat therapy improves lipid profile , blood pressure , and quality of life UNLABELLED OBJECTIVE ; Weight loss improves glycemic control , lipid profiles , and blood pressure in patients with type 2 diabetes . However , successful long-term weight loss is difficult for these patients , particularly those treated with insulin . The aim of this study was to assess the effect of orlistat , a gastrointestinal lipase inhibitor , on weight loss , glycemic control , and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients . RESEARCH DESIGN AND METHODS This study was a 1-year multicenter , r and omized , double-blind , placebo-controlled trial of orlistat ( 120 mg three times a day ) or placebo combined with a reduced-calorie diet in overweight or obese adults ( BMI 28 - 40 kg/m(2 ) ) with type 2 diabetes treated with insulin alone or combined with oral agents , but with suboptimal metabolic control ( HbA(1c ) 7.5 - 12.0 % ) . Outcome measurements included changes in body weight , glycemic control , blood pressure , and serum lipids . RESULTS ; After 1 year , the orlistat group lost significantly more weight ( -3.89 + /- 0.3 % of baseline body weight , means + /- SE ) than the placebo group ( -1.27 + /- 0.3 % , P < 0.001 ) . Orlistat treatment , compared with placebo , produced greater decreases in HbA(1c ) ( -0.62 + /- 0.08 vs. -0.27 + /- 0.08 % , P = 0.002 ) , fasting serum glucose ( -1.63 + /- 0.3 vs. -1.08 + /- 0.3 mmol/l , P = 0.02 ) , and the required doses of insulin and other diabetic medications . Orlistat also produced greater improvements than placebo in serum total cholesterol ( P = 0.0002 ) and LDL cholesterol concentrations ( P = 0.001 ) and LDL/HDL ratio ( P = 0.01 ) . CONCLUSIONS ; Orlistat therapy produces clinical ly significant weight loss , with improvements in glycemic control and cardiovascular disease risk factors , in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy Heart failure is the leading cause of hospitalization . Obesity is increasingly common and is a major public health problem . The aim of this study is to assess whether obese patients with heart failure can benefit from losing weight via an orlistat-assisted diet . This r and omized clinical trial included obese patients with ejection fractions < or = 40 % .  Orlistat and diet counseling were compared with diet counseling alone .  Twenty-one consecutive obese patients with heart failure were recruited . Significant improvement in 6-minute walk test ( 45.8 m ; 95 % confidence interval , 5.2 - 86.4 m ; p=0.031 ) , functional class ( -0.6+/-0.5 , p=0.014 ) , weight loss ( -8.55 kg ; 95 % confidence interval , -13.0 to -4.1 kg ; p<0.001 ) and also significant decreases in total cholesterol ( p=0.017 ) , low-density lipoprotein cholesterol ( p=0.03 ) , and triglycerides ( p=0.036 ) were observed in the orlistat group . Orlistat can promote significant weight loss and symptoms of relief in obese patients with heart failure , as measured by 6-minute walk test and functional capacity . The lipid profile improved . Orlistat was safe and well tolerated BACKGROUND AND AIM Previous studies have demonstrated that oxidative stress is increased in obese patients . The high-density lipoprotein ( HDL ) associated human paraoxonase 1 ( PON1 ) can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect . Our objective was to assess the effects of orlistat therapy combined with diet on body mass index ( BMI ) , waist circumference , lipid parameters , blood pressure , serum glucose level and PON1 activity . METHODS AND RESULTS A longitudinal , multicenter , r and omized study with and without orlistat treatment was performed . One hundred thirty nine otherwise healthy , obese subjects were divided in to two groups : 78 persons received orlistat ( 120 mg three times a day ) combined with diet while 61 persons were kept on diet only .  Anthropometrical parameters , serum lipid levels and PON1 activity were measured at baseline and after 6 months of treatment . BMI and waist circumference were reduced more pronouncedly in the orlistat group than in the control group . Patients receiving orlistat also had significantly greater improvements in fasting blood glucose levels and blood pressure . The orlistat-treated group showed a greater reduction in total cholesterol and triglyceride levels . In addition , the serum PON1 activity in these patients was significantly increased compared to the diet-only group . CONCLUSIONS The 6-month treatment with orlistat had a beneficial effect on the lipid profile and improved the antioxidant status by increasing serum PON1 activity . However , because of the limited therapeutic effectiveness , obese patients with hypercholesterolemia should receive additional lipid lowering medications CONTEXT Orlistat , a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30 % , may promote weight loss and reduce cardiovascular risk factors . OBJECTIVE 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 . DESIGN R and omized , double-blind , placebo-controlled study conducted from October 1992 to October 1995 . SETTING AND PARTICIPANTS 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 . INTERVENTION 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 r and omized 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 rer and omized 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 . MAIN OUTCOME MEASURES Body weight change and changes in blood pressure and serum lipid , glucose , and insulin levels . RESULTS A total of 1187 subjects entered the protocol , and 892 were r and omly 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 . CONCLUSIONS Two-year treatment with orlistat plus diet significantly promotes weight loss , lessens weight regain , and improves some obesity-related disease risk factors Objective : Orlistat and sibutramine are widely prescribed antiobesity agents that are approved for 2 years of continuous use . Previous 1–4-year r and omized , placebo-controlled trials of these drugs have reported average weight losses of < 5 kg , significant adverse effects and attrition rates of up to 60 % . The objective of this study was to determine the long-term persistence with orlistat and sibutramine therapy outside a clinical trial setting . Design , setting and patients : Population -based administrative data from British Columbia , Canada , were used to create an inception cohort of  orlistat and sibutramine users and determine the 2-year persistence with therapy . Main outcome measure : Persistence with therapy at 2 years . Drug discontinuation was defined as the failure to refill a prescription within 120 days . Patients discontinuing therapy were censored at the 60-day mark . Results : Nearly 17 000 users of orlistat and 3500 users of sibutramine were identified . For both orlistat and sibutramine , 1-year persistence rates were < 10 % and 2-year persistence rates were 2 % . Conclusion : This population -based , retrospective cohort analysis demonstrated very poor long-term persistence rates with orlistat and sibutramine and discontinuation rates that were much higher than those reported in clinical trials Aim : 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 Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid ( SFA ) intake in premenopausal and postmenopausal women or in blacks . We conducted a multicenter , r and omized , crossover- design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old . There were 46 men and 57 women , of whom 26 were black , 18 were postmenopausal women , and 16 were men > or = 40 years old . All meals and snacks , except Saturday dinner , were prepared and served by the research centers . The study was design ed to compare three diets : an average American diet ( AAD ) , a Step 1 diet , and a low-SFA ( Low-Sat ) diet . Dietary cholesterol was constant . Diet composition was vali date d and monitored by a central laboratory . Each diet was consumed for 8 weeks , and blood sample s were obtained during weeks 5 through 8 . The compositions of the three diets were as follows : AAD , 34.3 % kcal fat and 15.0 % kcal SFA ; Step 1 , 28.6 % kcal fat and 9.0 % kcal SFA ; and Low-Sat , 25.3 % kcal fat and 6.1 % kcal SFA . Each diet provided approximately 275 mg cholesterol/d . Compared with AAD , plasma total cholesterol in the whole group fell 5 % on Step 1 and 9 % on Low-Sat . LDL cholesterol was 7 % lower on Step 1 and 11 % lower on Low-Sat than on the AAD ( both P<.01 ) . Similar responses were seen in each subgroup . HDL cholesterol fell 7 % on Step 1 and 11 % on Low-Sat ( both P<.01 ) . Reductions in HDL cholesterol were seen in all subgroups except blacks and older men .  Plasma triglyceride levels increased approximately 9 % between AAD and Step 1 but did not increase further from Step 1 to Low-Sat . Changes in triglyceride levels were not significant in most subgroups . Surprisingly , plasma Lp(a ) concentrations increased in a stepwise fashion as SFA was reduced . In a well-controlled feeding study , stepwise reductions in SFA result ed in parallel reductions in plasma total and LDL cholesterol levels . Diet effects were remarkably similar in several subgroups of men and women and in blacks . The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population AIM To assess the effect of orlistat on body weight and concomitant diseases in patients with body mass index ( BMI ) of > 28 kg/m2 and poorly controlled type 2 diabetes , hypertension or hypercholesterolaemia . METHODS This trial was a six-month , r and omized , double-blind , placebo-controlled study of orlistat 120 mg three times daily plus a mildly reduced-calorie diet .  1004 obese patients ( BMI 28 - 40 kg/m2 ) were included by 253 private endocrinologists and received orlistat ( n = 499 ) or placebo ( n = 505 ) . Patients were stratified by concomitant disorder ( type 2 diabetes , n = 193 ; hypertension , n = 614 ; hypercholesterolaemia , n = 197 ) . Body weight , anthropometry , lipid and glycaemic control parameters and blood pressure . RESULTS After six months , orlistat produced a significantly greater weight loss than placebo in type 2 diabetes ( -4.2 % vs. -1.4 % ) , hypertension ( -6.2 % vs. -1.9 % ) and hypercholesterolaemia ( -5.5 % vs. -2.3 % ) groups ( p < 0.0001 for all ) . There was a greater decrease in HbA(1c ) in the type 2 diabetes group ( -0.54 vs. -0.18 % ; p = 0.002 ) and low-density lipoprotein (LDL)-cholesterol in the hypercholesterolaemia group ( -11.7 % vs. -4.5 % ; p = 0.004 ) with orlistat vs. placebo .  Early weight loss ( > or = 5 % at 12 weeks ) was associated with the highest weight loss in each group , and the highest decreases in HbA1c , LDL-cholesterol and diastolic blood pressure in patients with type 2 diabetes , hypercholesterolaemia and hypertension , respectively , at six months . The incidence of adverse events was similar for orlistat and placebo , except for certain generally well-tolerated gastrointestinal events that were more common with orlistat . CONCLUSION Orlistat plus a mildly reduced-calorie diet produced clinical ly meaningful weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes , hypertension or hypercholesterolaemia Orlistat lowers lipids and improves insulin sensitivity , but its effect on other metabolic syndrome related parameters is not known . To assess its influence on adiponectin , high sensitive C-reactive protein ( hs-CRP ) and other metabolic syndrome related parameters , this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index ( BMI ) matched controls . The orlistat group had greater changes in BMI , % body fat ( % BF ) , waist circumference , and insulin resistance , hs-CRP , leptin and adiponectin levels after one year on the program than the controls . After adjusting for % BF and waist circumference , change of serum leptin and adiponectin levels remained significantly different . It was found that orlistat could effectively manage obesity related co-morbidities , especially insulin resistance and atherosclerosis risk . It decreases leptin and increases adiponectin independent of % BF and waist circumference . Therefore , orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people OBJECTIVE : Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients . DESIGN : A 24 week multicentre , double-blind , r and omized , placebo-controlled trial . After a 2-week single-blind run-in period ( placebo+diet ( −600 kcal/day ; ≤30 % of calories as fat ) ) , 294 patients were su bmi tted to the hypocaloric diet and r and omly assigned to either orlistat 120 mg or placebo three times daily . Patients who completed the double-blind study ( n=255 ) were eligible for participation in a subsequent 24 week open-label orlistat extension phase . SUBJECTS : Patients with body mass index ( BMI ) 27–40 kg/m2 and hypercholesterolemia ( low-density-lipoprotein cholesterol , LDL-C , 4.1–6.7 mmol/l ) . MEASUREMENTS : Efficacy assessment s included weight loss , lipid levels , other cardiovascular risk factors and anthropometric parameters . Safety assessment s. RESULTS : Weight loss during run-in was similar in both groups . After r and omization , orlistat-treated patients lost significantly more weight  than placebo recipients : mean percentage weight loss from start of run-in to week 24 was−6.8 % in the orlistat group and −3.8 % in the placebo group ( P<0.001 ) . Moreover , more patients in the orlistat group than in the placebo group achieved clinical ly meaningful weight loss of ≥5 % ( 64 vs 39 % ) or ≥10 % ( 23 vs 13 % ) at week 24 . Treatment with orlistat was associated with significantly greater changes in total cholesterol ( −11.9 % vs −4.0 % ; P<0.001 ) and LDL-C ( −17.6 vs −7.6 % ; P<0.001 ) . For any category of weight loss during the double-blind treatment period , change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients , indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction ( P<0.001 ) . Adjunction of orlistat during the extension phase in patients who initially received placebo  induced a further decrease in weight , total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo , with the exception of a higher incidence of gastrointestinal events ( ≥1 event in 64 vs 38 % of patients ) . CONCLUSION : Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia BACKGROUND We undertook a r and omised controlled trial to assess the efficacy and tolerance of orlistat , a gastrointestinal lipase inhibitor , in promoting weight loss and preventing weight regain in obese patients over a 2-year period . METHODS 743 patients ( body-mass index 28 - 47 kg/m2 ) , recruited at 15 European centres , entered a 4-week , single-blind , placebo lead-in period on a slightly hypocaloric diet ( 600 kcal/day deficit ) . 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg ( three times a day ) or placebo for 1 year in conjunction with the hypocaloric diet . In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance ( eucaloric ) diet . FINDINGS From the start of lead-in to the end of year 1 , the  orlistat  group lost , on average , more bodyweight than the placebo group ( 10.2 % [ 10.3 kg ] vs 6.1 % [ 6.1 kg ] ; LSM difference 3.9 kg [ p < 0.001 ] from r and omisation to the end of year 1 ) . During year 2 , patients who continued with orlistat  regained , on average , half as much weight as those patients switched to placebo ( p < 0.001 ) . Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2 , compared with a mean regain of 2.5 kg in patients who continued on placebo ( p < 0.001 ) . Total cholesterol , low-density lipoprotein ( LDL ) cholesterol , LDL/high-density lipoprotein ratio , and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group . Gastrointestinal adverse events were more common in the orlistat group . Other adverse symptoms occurred at a similar frequency during both treatments . INTERPRETATION Orlistat taken with an appropriate diet promotes clinical ly significant weight loss and reduces weight regain in obese patients over a 2-year period . The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events OBJECTIVE : To assess the efficacy and tolerability of orlistat ( Xenical ® ) in producing and maintaining weight loss over a 12-month period . DESIGN : Patients were r and omized to double-blind treatment with either orlistat 120 mg or placebo three times daily , in conjunction with a low-energy diet , for 12 months . SETTING : Five centres in the UK.SUBJECTS : 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg ( range 74–144 kg ) . INTERVENTIONS : All patients were prescribed a low-energy diet , providing 30 % of energy from fat , design ed to produce an individually tailored energy deficit of approximately 600 kcal/day , for a run-in period of 4 weeks and then 12 months , plus orlistat 120 mg or placebo three times daily . MAIN OUTCOME MEASURES : Change in body weight ( the primary efficacy parameter ) , waist circumference and adverse events were review ed regularly , together with serum lipids , insulin , glucose and plasma levels of fat-soluble vitamins and β carotene . RESULTS : Based on an intent-to-treat analysis , after 1 y of treatment patients receiving orlistat had lost an average of 8.5 % of their initial body weight compared with 5.4 % for placebo-treated patients ; 35 % of the orlistat group lost at least 5 % of body weight compared with 21 % of the placebo group ( P<0.05 ) , and 28 % and 17 % , respectively ( P=0.04 ) lost at least  10 %  of body weight . Orlistat-treated patients showed significant decreases ( P<0.05 ) in serum levels of total cholesterol , low density lipoprotein cholesterol , and in the low density lipoprotein : high density lipoprotein ratio in comparison with placebo . Both groups had similar adverse-event profiles , except for gastrointestinal events , which were 26 % more frequent in the orlistat group but were mostly mild and transient . To maintain normal plasma levels of fat-soluble vitamins , supplements of vitamins A , D and E were given to 1.8 % , 8.0 % and 3.6 % , respectively , of orlistat-treated patients , compared with 0.9 % of placebo-treated patients for each vitamin type . After 1 y , the decrease in vitamin E and β carotene was significantly greater in orlistat-treated patients compared with those receiving placebo ( P<0.001 ) . No significant change was found in the mean vitamin E : total cholesterol ratio in either group after 52 weeks . Conclusions : Orlistat , in conjunction with a low-energy diet , produced greater and more frequent significant weight loss  than placebo during 1 y of treatment . One-third of orlistat-treated patients achieved clinical ly relevant weight loss ( ≥5 % initial body weight ) . There was also an improvement in relevant serum lipid parameters . Fat-soluble vitamin supplements may be required during chronic therapy . Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity Co-existence of obesity and type 2 DM exacerbates metabolic and other remediable health consequences further . Various pharmacological therapies have been adopted when changing of lifestyle fail to achieve target glycaemic control . Our objective is to find out whether Orlistat can reduce both weight and need for oral hypoglycaemic agent ( OHA ) and improves glycaemic status , lipid disorders , blood pressure in Bangladesh type 2 DM with obesity . In this center , open-label , r and omized , controlled pilot trial 36 type 2 patients with obesity were enrolled . All patients aged 40 - 65 years had BMI > 25 kg/m2 taking sulfonylureas and hypocalorie diet . Twenty one r and omly cases were treated with orlistat 120 mg three times daily for 6 months and 15 without orlistat as control .  Body weight , waist circumferances , fasting blood sugar , HbAlc , serum lipids , blood pressure and dose of drugs were monitored at 0,12 , 24 weeks . After 6 months , orlistat group showed non-significant weight loss than control group ( 3.95 % vs 1.42 % from base lines ) , but showed significant reduction of waist circumference ( 6 % vs 0.63 % , p<0.01 vs p>0.05 from base line ) . Orlistat group had significant improvement in glycaemic status ( HbA1c changes : 22.37 % vs 13.38 % , p<0.001 vs p>0.05 and FBS changes : 21.76 % vs 22.95 % , p<0.01vs p<0.05 ) . Lipid profile had reduced significantly from base lines ( Chol : 19.31 % vs 9.12%,p<0.001vs > 0.05 ; LDL Chol : 24.99 % vs 19.09 % , p<0.001 vs p<0.01 ; Triglyceride : 34.48 % vs 12.61 % , p<0.001 vs p>0.05 ) . Diastolic pressure had improved significantly in orlistat group ( 6.73 % vs 3.70 % , p<0.01 vs > 0.05 ) . Reduction of OHA doses were found in both groups . Thus orlistat can be used as an adjuvant therapy with other OHA in managing glycaemic control , lipid profiles and blood pressure BACKGROUND High-density lipoprotein ( HDL ) includes discrete subfractions . HDL exhibits anti-atherogenic properties , which have been partly linked to the activity of HDL-associated enzymes , such as the lipoprotein associated phospholipase A(2 ) ( HDL-LpPLA(2 ) ) and paraoxonase-1 ( PON1 ) . OBJECTIVE We assessed in an open-label r and omised study the effect of orlistat and ezetimibe , alone or in combination , on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects ( body mass index > 28 kg/m(2 ) ) with hypercholesterolemia [ total cholesterol > 200 mg/100 ml ( 5.2 mmol/l ) ] . METHODS Eighty-six people were prescribed a low-fat low-calorie diet and were r and omly allocated to receive orlistat 120 mg , three times daily ( O group ) , ezetimibe 10 mg/day ( E group ) or both ( OE group ) for 6 months . HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method . RESULTS Levels of HDL cholesterol ( HDL-C ) and apolipoprotein AI did not change significantly in any group . In group O the cholesterol concentration of HDL-2 subclass increased significantly , while the cholesterol of HDL-3 subclass decreased significantly . In groups E and OE HDL-2 subclass did not significantly change , while the cholesterol concentration of HDL-3 subclass decreased significantly . We observed a non-significant decrease in the HDL-LpPLA(2 ) and PON1 activity in all groups . However , the ratios of both enzyme activities to low-density lipoprotein cholesterol ( LDL-C ) levels ( an index of atherogenicity ) significantly increased in all groups . CONCLUSION Although HDL-C levels did not change after treatment with orlistat and ezetimibe , alone or in combination , there were alterations of the HDL-2 and HDL-3 subclasses . The activity of HDL-LpPLA(2 ) and PON1 per mg LDL-C increased significantly in all groups OBJECTIVE Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases . Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone . Therefore , we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration . RESEARCH METHODS AND PROCEDURES Cholesterol absorption from a st and ardized meal , containing 72 mg of cholesterol , was determined in 18 subjects with class II abdominal obesity ( BMI , 35.0 to 39.9 kg/m(2 ) ) by simultaneous administration of intravenous ( [ (2)H(6 ) ] cholesterol ) and oral ( [ (2)H(5 ) ] cholesterol ) cholesterol tracers . In protocol 1 ( n = 9 ) , cholesterol absorption was determined on two different occasions , 10 to 20 days apart , to assess the reproducibility of the tracer method . In protocol 2 ( n = 9 ) , cholesterol absorption was determined with and without orlistat therapy in a prospect i ve , r and omized , crossover design to assess the effect of orlistat on cholesterol absorption . RESULTS In protocol 1 , cholesterol absorption from the test meal was the same on both occasions ( 53 + /- 5 % and 51 + /- 5 % ) . In protocol 2 , orlistat treatment caused a 25 % reduction in cholesterol absorption , from 59 + /- 6 % to 44 + /- 5 % ( p < 0.01 ) . DISCUSSION These data demonstrate that orlistat inhibits dietary cholesterol absorption , which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself Objective 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 , prospect i ve , r and omized , double-blind , placebo-controlled , multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives . Interventions Participants were r and omized 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 . Main outcome measures 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 ⩾ 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 ) . Conclusion A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction AIM To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks ( 6 months ) with orlistat ( 120 mg t.i.d . ) , in conjunction with a hypocaloric diet plus behavioural counselling , than when treated by placebo ( t.i.d . ) plus similar instructions . The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of  orlistat . DESIGN Double-blind , parallel , r and omized , placebo-controlled , multicentre study . SUBJECTS Obese , non-insulin-dependent diabetic patients , aged 18 - 70 years old , with BMI > 27 kg/m2 , evaluated at 10 Latin-American centres , in five countries .  EFFICACY AND TOLERABILITY MEASUREMENTS : After screened , eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet . On day 0 , patients were r and omized to orlistat or placebo for 24 weeks . At each visit , body weight , blood pressure and waist circumference were measured . At the screening visit , baseline visit ( week 0 ) , and at weeks 8 , 16 and 24 , a central laboratory was in charge of measuring fasting glucose and insulin , HbA1c , postpr and ial glucose and insulin , fasting total cholesterol , HDL-cholesterol , LDL-cholesterol , triglycerides , and postpr and ial triglycerides . Other safety laboratory assessment s were measured locally at the screening visit , baseline visit and at the end of the study . Adverse events were assessed at each visit from baseline . RESULTS After 24 weeks of treatment , the orlistat group lost an average of 4.7 % of initial body weight vs. 3.0 % in the placebo group ( p = 0.0003 ) . A greater weight loss was achieved in the orlistat compared with the placebo group ( 4.24 + /- 0.23 vs. 2.58 + /- 1.46 kg , p = 0.0003 ) . Almost twice as many patients receiving orlistat ( 30 % vs. 17 % ) lost > or = 5 % of initial body weight ( p = 0.003 ) . Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control , as reflected in decreases in HbA1c ( p = 0.04 ) , fasting plasma glucose ( p = 0.036 ) and postpr and ial glucose ( p = 0.05 ) . Orlistat-treated patients had a mean decrease in glucose levels of 1.00 + /- 0.34 mmol/l [ 3.7 % ] vs. 0.01 + /- 0.30 mmol/l for placebo group , at week 24 and an absolute decrease of HbA1c of 0.61 + /- 0.15 vs. a decrease of 0.22 + /- 0.14 % in the placebo group . Orlistat therapy also result ed in significantly greater improvements than placebo in lipid profile , with reductions in total cholesterol ( p = 0.0001 ) and LDL-cholesterol ( p = 0.002 ) . Mild to moderate transient gastrointestinal events were reported , mainly with orlistat treatment , but their association with withdrawal from the study was low . CONCLUSION Orlistat is a useful and an effective therapy in obese diabetic patients , promoting clinical ly significant weight loss and improved glycaemic control and lipid profile INTRODUCTION Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes , hypertension , dyslipidemia and gallbladder disease . OBJECTIVE To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia , treated over a period of 6 months . METHODOLOGY In a 6-month , multicenter ( 10 centers in Portugal ) , double-blind , parallel , placebo-controlled study , 166 patients , aged 18 - 65 years , body mass index ( BMI ) > or = 27 kg/m2 , LDL cholesterol > 155 mg/dl , were r and omized to a reduced calorie diet ( 600 kcal/day  deficit ) plus orlistat three times a day or placebo .  Exclusion criteria included triglycerides > 400 mg/dl , severe cardiovascular disease , uncontrolled hypertension , type 1 or 2 diabetes under pharmacological treatment , and gastrointestinal or pancreatic disease . RESULTS The mean difference in weight from baseline was 5.9 % ( 5.6 kg ) in the orlistat group vs. 2.3 % ( 2.2 kg ) in the placebo group . In the orlistat group 49 % of patients achieved 5 - 10 % weight loss and 8.8 % achieved > 10 % . The orlistat group showed a significant reduction in total and LDL cholesterol , with similar changes for HDL in both treatment groups . The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group , leading to discontinuation in 7 patients . CONCLUSION Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight , BMI and lipid parameters The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome ( PCOS ) . Twenty-one Caucasian women with PCOS [ mean ( + /-SEM ) age 27 + /- 0.9 yr and body mass index 36.7 + /- 3.3 kg/m(2 ) ] participated in this prospect i ve , r and omized , open-labeled study . All subjects had an 8-wk run-in period of dietary modification and then r and omized to receive either metformin ( 500 mg three times daily ) or orlistat ( 120 mg three times daily ) for 3 months . Weight , blood pressure , and fasting blood sample s were taken at screening , r and omization , and on completion . Insulin resistance ( IR ) was calculated using the homeostasis model of assessment (HOMA)-IR method [ HOMA-IR = ( insulin x glucose)/22.5 ] . The results are expressed as mean + /- SEM . When compared with baseline , treatment with both orlistat [ 93.5 + /- 11.5 ng/dl ( 3.24 + /- 0.4 nmol/liter ) vs. 114.5 + /- 11.5 ng/dl ( 3.97 + /- 0.4 nmol/liter ) , P = 0.039 ] and metformin [ 97.2 + /- 11.5 ng/dl ( 3.37 + /- 0.4 nmol/liter ) vs. 120.0 + /- 8.7 ng/dl ( 4.16 + /- 0.3 nmol/liter ) , P = 0.048 ] produced a significant reduction in total testosterone . Treatment with orlistat produced a 4.69 % reduction in weight ( 99.0 + /- 6.0 vs. 94.6 + /- 6.1 kg , P = 0.002 ) , and this reduction was more significant than the reduction produced by metformin ( 4.69 vs. 1.02 % , P = 0.006 ) . There was no significant reduction seen after either treatment group for fasting insulin , HOMA-IR , SHBG , or any of the lipid parameters studied . In this study , orlistat produced a significant reduction in weight and total testosterone . The reduction in total testosterone was similar to that seen after treatment with metformin . Therefore , orlistat may prove to be a useful adjunct in the treatment of PCOS
target: Orlistat  reduced body weight ( weighted mean difference : −2.12 , p < 0.001 ) , total‐cholesterol ( weighted mean difference : −0.30 mmol/L , p < 0.001 ) , low‐density lipoprotein cholesterol ( weighted mean difference : −0.27 mmol/L , p < 0.001 ) , high‐density lipoprotein cholesterol ( weighted mean difference : −0.034 mmol/L , p < 0.001 ) and triglyceride ( weighted mean difference : −0.09 mmol/L , p < 0.001 ) concentrations , while no effect on lipoprotein(a ) was observed .
  Total‐ and low‐density lipoprotein cholesterol‐lowering were associated negatively with duration of orlistat treatment and positively with body weight changes .
  In conclusion , Orlistat treatment slightly reduces cholesterol and triglyceride levels , but not lipoprotein(a ) levels .
  Total‐ and low‐density lipoprotein cholesterol levels reductions are more consistent in patients with greater body weight reduction and shorter duration of orlistat treatment .
  We investigated the efficacy of orlistat on plasma lipids and body weight in a meta‐ analysis of 33 studies including 9732  participants .Orlistat  was associated with a slight but significant decrease in body weight , plasma cholesterol and triglyceride concentrations , whereas plasma Lp(a ) levels were not affected by orlistat treatment .
  Greater body weight reduction and lower duration of orlistat treatment promoted more consistent plasma total‐ and LDL‐cholesterol lowering
background: & NA ; Orlistat , an inhibitor of intestinal lipase , promotes body weight reduction .
  The lipid‐lowering efficacy of orlistat is controversial and the effect of orlistat‐induced body weight reduction on lipid changes has not been explored in meta‐regression analyses .
  HighlightsOrlistat is an inhibitor of intestinal lipase promoting body weight reduction , but whose lipid‐lowering efficacy is controversial .