Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Orlistat, a gastrointestinal lipase inhibitor, in therapy of obesity with concomitant hyperlipidemia. The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat Dose-Ranging Study Group. Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients Orlistat in the long-term treatment of obesity in primary care settings. A randomized double-blind study comparing the efficacy and safety of orlistat versus placebo in obese patients with mild to moderate hypercholesterolemia. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Orlistat inhibits dietary cholesterol absorption. Role of Orlistat in the Treatment of Obese Patients With Type 2 Diabetes: A 1-year randomized double-blind study Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Treatment with orlistat reduces cardiovascular risk in obese patients One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor
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 Orlistat , a gastrointestinal lipase inhibitor , decreases fat absorption and thus it reduces caloric intake . The objectives of this placebo-controlled , double-blind , multicentre trial were to evaluate the efficacy of orlistat in terms of weight reduction , the effects on serum lipid levels and its tolerability profile .  119 obese patients ( body mass index , BMI > or = 30 kg/m2 ) with hyperlipidemia ( LDL-cholesterol > or = 4 , 2 mmol/l ) were r and omized to receive either orlistat capsules 120 mg ( n = 60 ) or placebo capsules ( n = 59 ) , three times daily , during 24 weeks . All patients were also on a mild hypocaloric diet .  Mean weight reduction was 10.75 kg ( 10.7 % ) in orlistat group and 7.34 kg ( 7.5 % ) in placebo group . All serum lipid parameters improved in the orlistat group . The only adverse event more frequently noted with orlistat was stool fat .  Orlistat in combination with diet provides increased weight loss than diet alone , improvements of serum lipids in subjects with hyperlipidemia and it has a good tolerability profile without systemic effects 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 OBJECTIVE To evaluate efficacy and tolerability of the lipase inhibitor Orlistat ( Ro 18 - 0647 ) in doses of 10 , 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30 % of calories as fat . DESIGN 4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind , placebo-controlled , r and omized treatment period . SETTING S Five European outpatient clinics specializing in endocrinology and /or the treatment of obesity , one central laboratory . SUBJECTS Of 237 healthy obese subjects meeting the inclusion criteria , 188 showed compliance to the diet during the run-in period and were r and omized for the treatment period . MAIN OUTCOME MEASURES Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group . Secondary efficacy criteria were changes in serum total , HDL- and LDL-cholesterol . RESULTS Compared to placebo a mean ( + /- s.e . ) additional weight loss of 0.63 + /- 0.54 kg with 30 mg a day ( P = 0.246 ) , 0.71 + /- 0.55 kg with 180 mg a day ( P = 0.190 ) and 1.75 + /- 0.54 kg with 360 mg a day was seen ( P = 0.001 ) or Orlistat was observed . Overall data indicated dose-dependency . Small decreases were seen in total and LDL-cholesterol ( significant in the 180 and 360 mg a day groups ) and LDL- to HDL-cholesterol ratio ( significant in the 360 mg a day group only ) . Mild , mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients . No marked laboratory abnormalities were shown , including the lipid-soluble vitamins A , D and E. CONCLUSION Orlistat , in an apparently dose-dependent manner , leads to additional weight loss compared to diet alone and overall , is well tolerated 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 OBJECTIVE To determine the weight-reducing efficacy of orlistat , a novel gastrointestinal lipase inhibitor , and to define the optimal dosage regimen and establish the tolerability of the drug when used for a 6-month treatment period . METHODS The study was a multicentre r and omised , double-blind , parallel group in design and involved 676 obese male and female subjects aged at least 18 years with a body mass index between 28 and 43 kg x m(-2 ) Following a 5-week placebo run-in period , subjects were r and omised to receive orlistat 30 mg , 60 mg , 120 mg , 240 mg or matching placebo three times a day ( tid ) for 24 weeks during meals . Patients were maintained on a mildly hypocaloric diet throughout the study period . The primary efficacy parameter was body weight change over time . RESULTS Orlistat result ed in a significantly greater mean loss of body weight than observed in the placebo group . In absolute terms , mean weight loss was greatest in the 120 mg group ( 9.8 % ) . More orlistat- than placebo-treated patients lost > 10 % of initial body weight ( 37 % of the 120 mg group vs 19 % of the placebo group ) . Orlistat was well tolerated . Predictably , in view of its known pharmacological effects , more orlistat-treated patients experienced gastrointestinal events . Mean levels of vitamins A , D and E , and beta-carotene remained within the clinical reference ranges in all treatment groups and rarely required supplementation . After 24 weeks , plasma concentrations of orlistat  were either non-measurable or detected at the assay 's limit of quantitation . CONCLUSION Orlistat treatment results in a dose-dependent reduction in body weight in obese subjects and is well tolerated . Orlistat 120 mg tid represents the optimal dosage regimen OBJECTIVES : Orlistat , an intestinal lipase inhibitor , has recently been approved by the US Food and Drug Administration for treatment of obesity . The effects of orlistat on hepatobiliary function have not been previously defined . A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet . METHODS : A total of 23 obese ( BMI 30–41 kg/m2 ) subjects were r and omized to a double blind t.i.d . treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet ( 1200–1500 kcal/day ) . The study was design ed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat .  Cholesterol saturation , bile composition , and gallbladder motility were measured . RESULTS : At the end of the treatment period , mean weight loss of 3.8 kg was achieved in the orlistat group ( vs 2.3 kg with placebo , p = NS ) . Total bile acid concentration decreased significantly with placebo ( –18.57 ± 6.99 mmol/L ; 95 % CI = –32.26 to –4.87 ) , but not with orlistat . Biliary phospholipid concentration decreased significantly with placebo ( −4.38 ± 1.91 mmol/L ; 95 % CI = –8.13 to –0.64 ) but not with orlistat . Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups . Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group . CONCLUSIONS : Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids . Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function . We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat 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 evaluate the long-term efficacy and tolerability within primary care setting s of orlistat , a gastrointestinal lipase inhibitor , for the treatment of obesity . DESIGN R and omized , double-blind , placebo-controlled , multicenter study . PARTICIPANTS A group of 796 obese patients ( body mass index , 30 - 44 kg/m2 ) , treated with placebo 3 times a day ( TID ) , 60 mg of orlistat TID , or 120 mg of orlistat TID , in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year . SETTING Seventeen primary care centers in the United States . MAIN OUTCOME MEASURES Changes in body weight and obesity-related disease risk factors . RESULTS Patients treated with orlistat lost significantly more weight ( 7.08 + /- 0.54 and 7.94 + /- 0.57 kg for the 60-mg and 120-mg orlistat groups , respectively ) than those treated with placebo ( 4.14 + /- 0.56 kg ) in year 1 ( P<.001 ) and sustained more of this weight loss during year 2 ( P<.001 ) . More patients treated with orlistat lost 5 % or more of their initial weight in year 1 ( 48.8 % and 50.5 % of patients in the 60-mg and 120-mg groups , respectively ) compared with placebo ( 30.7 % ; P<.001 ) , and approximately 34 % of patients in the orlistat groups sustained weight loss of 5 % or greater over 2 years compared with 24 % in the placebo group ( P<.001 ) . Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated , although treatment result ed in a higher incidence of gastrointestinal events . CONCLUSIONS This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care setting 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 BACKGROUND We undertook a r and omised controlled trial to assess the efficacy and tolerability of orlistat , a gastrointestinal lipase inhibitor , in promoting weight loss and preventing weight regain in obese patients over a 2-year period . 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 BACKGROUND & AIMS Few controlled studies have addressed the issue of effective medical treatment for nonalcoholic fatty liver disease ( NAFLD ) . We herein assessed the effect of orlistat in patients with NAFLD . METHODS We performed a r and omized , double-blind , placebo-controlled study on 52 patients with NAFLD diagnosed by ultrasound ( US ) and confirmed by liver biopsy ( 40 patients ) . The patients were r and omized to receive either orlistat ( 120 mg 3 times daily for 6 months ) or placebo . All patients participated in an identical behavioral weight loss program . All patients underwent monthly evaluation by abdominal US ; liver enzyme levels , lipid profiles , insulin levels , and anthropometric parameters were monitored , and all patients underwent nutritional follow-up evaluation . Twenty-two patients underwent a second liver biopsy examination at the end of the study . RESULTS Fifty-two patients were recruited and 44 ( mean age , 47.7 y ; mean body mass index , 33 ) completed the study .  Serum glucose and insulin levels ( P<.03 ) were significantly higher in the orlistat group , which also presented a higher degree of fibrosis . Body mass index was reduced significantly in each group , with a nonsignificant difference between the groups . Serum alanine transaminase ( ALT ) levels decreased significantly in both groups , with an almost 2-fold reduction in the orlistat group ( 48 % vs 26.4 % ) . There was a statistically significant reversal of fatty liver by US only in the orlistat group ( P<.05 ) . CONCLUSIONS Orlistat improves serum ALT levels and steatosis on US in NAFLD patients , beyond its effect on weight reduction 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 Obesity is an important risk factor for type 2 diabetes . Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors , but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise . The purpose of this study was to assess the impact of treatment with orlistat , a pancreatic lipase inhibitor , on weight loss , glycemic control , and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications . RESEARCH DESIGN AND METHODS In a multicenter 57-week r and omized double-blind placebo-controlled study , 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years , had a BMI of 28–40 kg/m2 , and were clinical ly stable on oral sulfonylureas .  Changes in body weight , glycemic control , lipid levels , and drug tolerability were measured . RESULTS After 1 year of treatment , the orlistat group lost 6.2 ± 0.45 % ( mean ± SEM ) of initial body weight vs. 4.3 ± 0.49 % in the placebo group ( P < 0.001 ) . Twice as many patients receiving orlistat ( 49 vs. 23 % ) lost ≥ 5 % of initial body weight ( P < 0.001 ) . Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control , as reflected in decreases in HbA1c ( P < 0.001 ) and fasting plasma glucose ( P < 0.001 ) and in dosage reductions of oral sulfonylurea medication ( P < 0.01 ) . Orlistat therapy also result ed in significantly greater improvements than placebo in several lipid parameters , namely , greater reductions in total cholesterol , ( P < 0.001 ) , LDL cholesterol ( P < 0.001 ) , triglycerides ( P < 0.05 ) , apolipoprotein B ( P < 0.001 ) , and the LDL-to-HDL cholesterol ratio ( P < 0.001 ) . Mild to moderate and transient gastrointestinal events were reported with orlistat therapy , although their association with study withdrawal was low . Fat-soluble vitamin levels generally remained within the reference range , and vitamin supplementation was required in only a few patients . CONCLUSIONS Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinical ly meaningful weight loss and maintenance of weight loss , improved glycemic control , and improved lipid profile 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 To study the efficacy of orlistat , as an adjunct to dietary modification , in weight reduction and modification of cardiovascular risk factors in obese patients after 1 year of treatment . Design A total of 3132 obese patients ( body mass index 28–43 kg/m2 ) were evaluated in an analysis of pooled data from five r and omized , double-blind ,  placebocontrolled trials of orlistat in conjunction with a hypocaloric diet . All studies included a 4-week , single-blind , placebo lead-in period during which patients followed a mildly hypocaloric diet , after which they were r and omized to double-blind treatment with orlistat 120 mg three times a day ( tid ) or placebo for 1 year . Results After 1 year , orlistat 120 mg tid produced significantly more weight loss than placebo ( 9.2 % vs 5.8 % ; P < 0.001 ) . Furthermore , a greater proportion of orlistat-treated patients lost > 5 % or > 10 % of their initial body weight compared to placebo ( 69.6 % vs 51.9 % ; P < 0.001 and 42.1 % vs 22.7 % ; P < 0.001 , respectively ) . Improvements in cardiovascular risk factors were observed during a 4-week placebo lead-in period . However , following r and omization , orlistat-treated patients had significantly greater improvements than placebo-treated patients in several lipid parameters including total cholesterol , low-density lipoproteincholesterol , triglycerides , and apolipoprotein B. In addition , orlistat had a beneficial effect on oral glucose tolerance tests status , waist circumference and systolic and diastolic blood pressure . Orlistat was well tolerated and had a similar safety profile to placebo 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
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
& 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 .