Orlistat, a gastrointestinal lipase inhibitor, in therapy of obesity with concomitant hyperlipidemia. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss Role of Orlistat in the Treatment of Obese Patients With Type 2 Diabetes: A 1-year randomized double-blind study The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. A one-year trial to assess the value of orlistat in the management of obesity. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor Orlistat in the long-term treatment of obesity in primary care settings. Gastrointestinal side effects of orlistat may be prevented by concomitant prescription of natural fibers (psyllium mucilloid) Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat Dose-Ranging 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 overweight and obese patients with type 2 diabetes treated with metformin. 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 Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Effects of a weight-reduction program with orlistat on serum leptin levels in obese women: A 12-week, randomized, placebo-controlled study. The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes.
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 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 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 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 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 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 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 OBJECTIVES This paper describes the methodology of a multicentre study design ed to assess the efficacy and tolerability of orlistat 120 mg tid as therapy for inducing weight loss in excess of that achieved with a moderately calorie-restricted diet alone . The results from a single centre are presented to illustrate the nature of the response . DESIGN This was a double-blind , r and omized , parallel-group , placebo-controlled multicentre study . A four-week , single-blind , placebo run-in period preceded a 52 week double-blind treatment period during which patients received either orlistat or placebo three times a day . At the start of the run-in period , all patients were placed on a diet containing approximately 30 % of calories as fat and design ed to cause an energy deficit of approximately 600 kcal/d . SUBJECTS Patients of either sex , more than 18 y of age , with a body mass index ( BMI ) between 30 and 43 kg/m2 were eligible for enrolment . MEASUREMENTS Efficacy assessment s included : measurements of body weight ; anthropometry ; quality of life ; blood pressure ; serum lipids ; fasting serum glucose and insulin . Safety assessment s included : adverse events ; vital signs ; ECG ; renal and gallbladder ultrasound ; haematology ; serum biochemistry . OUTCOME In the single centre there was a reduction in body weight of 5.5 + /- 4.5 ( s.d . ) kg ( 5.7 % reduction ) in the placebo group and 8.6 + /- 5.4 kg in the orlistat-treated group ( 8.4 % reduction ) by six months . Thereafter , the placebo group tended to relapse whereas the orlistat group maintained their loss ( 2.6 % vs 8.4 % reduction from initial value at 52 weeks ) . Total and LDL cholesterol fell by 0.05 mmol/l ( 1.6 % ) and 0.14 mmol/l ( 4.2 % ) , respectively , in orlistat treated patients . The drop-out rate was 48 % in the  placebo  group and 39 % in the orlistat group . Intestinal symptoms related to orlistat were significantly increased compared to placebo but were well tolerated . Fat soluble vitamin levels remained within the normal range in the treatment group ; the reduction seen in alpha-tocopherol levels in patients receiving orlistat was normalized by the decrease in plasma cholesterol concentrations . Beta-carotene and vitamin D concentrations also decreased in orlistat-treated patients . CONCLUSIONS This preliminary analysis suggests that orlistat , when used with a health-promoting low-fat and moderately energy-restricted diet , confers advantages in the long-term management of obesity 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 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 OBJECTIVES : This placebo-controlled open study was design ed to test the hypothesis that most of the gastrointestinal ( GI ) side events induced by treatment of obese patients with orlistat ( a gastrointestinal lipase inhibitor ) could be prevented or ameliorated by concomitant use of natural fibers ( psyllium mucilloid ) . DESIGN : Two groups of obese women ( BMI > 27 kg/m2 ) were treated with orlistat 120 mg three times a day . One group ( A , n=30 ) was r and omized to receive orlistat and , approximately 6.0 g of orange-flavored psyllium mucilloid dissolved in water and the other group ( B , n=30 ) received orlistat and orange-flavored placebo . At the end of 30 days and 2 weeks of washout , group A switched to placebo and group B received psyllium while continuing orlistat three times a day . SUBJECTS : Sixty professional women , more than 21-y-old with a body mass index ( BMI ) between 27.3 and 48.0 kg/m2 , who were not receiving any other medication . MEASUREMENTS : Assessment s included weekly visits to attending physician , filling a form in which GI events were recorded , monthly measurements of body weight , blood pressure and serum lipids . The frequency and severity of GI events were evaluated by a score system , based on information provided by the patients . RESULTS : Both groups A and B significantly lost ( P<0.01 ) weight after 60 days of orlistat ( A=96.8 to 94.9 kg and B=98.7 to 96.5 kg ) . Similarly , BMI values declined significantly in both groups . While in the psyllium plus orlistat group ( group A ) the mean ±s.e.m . of the scores reflecting GI events was 13.0±1.8 , the placebo plus orlistat group ( B ) had a value of 35.9±2.7 ( P<0.01 ) . When the reverse situation was instituted the placebo and orlistat group presented a mean score of 36.1±3.6 and the psyllium plus orlistat a mean score of 8.9±1.5 ( P<0.01 ) . CONCLUSIONS : Psyllium hydrophilic mucilloid concomitantly prescribed to obese patients receiving 120 mg of orlistat three times a day is an effective and safe adjunct therapy that is helpful in controlling the GI side effects of this pancreatic lipase inhibitor 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 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 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 : 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 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 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 BACKGROUND Leptin , which has been identified as an antiobesity hormone , regulates body weight by controlling food intake and energy expenditure via the hypothalamic-pituitary-gonadal axis . It appears that leptin may be an important factor in obesity management . Orlistat , a pancreatic lipase inhibitor , could reduce fat absorption and promote weight loss due to leptin metabolism . OBJECTIVE The purpose of this study was to investigate the effects of orlistat therapy on serum leptin levels . METHODS Obese women ( body mass index [ BMI ] , 30 kg/m(2 ) ) aged 18 to 50 years were r and omly assigned to receive 12 weeks of oral treatment with diet-orlistat ( 120 mg TID ) ( DO group ) or diet-placebo ( DP group ) . During the treatment period , patients were asked to eat a balanced diet of -1200 to 1600 kcal/d . Body composition was determined by bioelectrical impedance . Serum leptin levels were measured using radioimmunoassay at baseline and at study end . RESULTS A total of 24 patients entered the study ; 14 patients ( mean [ SE ] BMI , 37.7 [ 1.1 ] kg/m(2 ) ) received orlistat and 10 patients ( mean [ SE ] BMI , 39.4 [ 1.3 ] kg/m(2 ) ) received placebo . Compared with baseline , mean percentages of loss of body weight and fat mass after 12 weeks of treatment were significant in the DO group ( 9.1 % and 14.8 % , respectively ; both P = 0.001 ) and in the DP group ( 9.5 % and 17.6 % ; both P = 0.005 ) . The between-group differences were not statistically significant . Mean ( SE ) serum leptin levels also decreased significantly after treatment in the DO group ( 16.2 [ 1.2 ] vs 9.0 [ 1.0 ] ng/mL ; P = 0.001 ) and in the DP group ( 19.3 [ 2.1 ] vs 9.7 [ 1.4 ] ng/mL ; P = 0.005 ) . The between-group difference was not statistically significant . CONCLUSIONS In this study of obese women , orlistat treatment was associated with a similar decrease in body weight , fat mass , and serum leptin levels as placebo over a 12-week period . In this regard , short-term orlistat therapy may not provide an additional effect on serum leptin levels , and reduction in leptin levels were closely related to the decrease in fat mass Purpose Comparing the effects of metformin or orlistat on hormone , lipid profile and ovulation status in obese women with polycystic ovary syndrome . Methods A total of 80 women were prospect ively recruited to receive either metformin ( n = 40 ) or orlistat ( n = 40 ) . Weight , BMI , waist , serum LH , total serum testosterone and lipid profile were assessed at baseline and after 3 months . The subjects ’ ovulatory status was assessed after 3 months . Results There was no significant difference in ovulation between the two treatment groups ( 30 % vs 15 % ) . Treatment with either drug showed a significant decline in body weight , BMI ( Body Mass Index ) , and waist circumference , but the degree of decline in both groups was the same . Patients who were treated with orlistat , showed a significant reduction in total testosterone and serum lipid . Women in metformin group showed a significant reduction in serum LH . Conclusions Both metformin and orlistat showed a similar effect on weight loss and ovulation rates The effect of Orlistat , a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time , on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption . After a placebo run-in period 14 patients were r and omized to a 12-week treatment period on Orlistat 360 mg per day ( mean body weight 93.1 + /- 9.8 kg ) or placebo ( mean body weight 90.7 + /- 10.5 kg ) . At r and omization and after 12 weeks body weight , body composition , thyroid hormones , catecholamines , insulin-like growth factor I ( IGF-I ) and IGF-binding protein 3 were measured . During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication , 15 g lactulose and 25 g xylose , blood levels of glucose , insulin , c-peptide , glucagon , triglycerides , free fatty acids , cholecystokinin , pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured . Weight loss was 4.2 + /- 3.5 kg in the Orlistat group versus 3.0 + /- 1.9 kg in the placebo group . Fat mass decreased to an equal degree , whereas lean body mass remained stable . No differences were found for thyroid hormones , catecholamines , IGF-I and IGFBP-3 levels . By comparing the areas under the curve ( AUC ) and the peak levels at r and omization ( acute effects ) of insulin and c-peptide a tendency was found to be increased in the Orlistat group , whereas those of xylose were increased significantly , suggesting faster gastric emptying after Orlistat . No differences were found in the other parameters . By comparing the changes in responses ( longer term effects ) no significant differences were found . In conclusion , the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients 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 WHAT IS KNOWN AND OBJECTIVE The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients , and a pharmacological treatment is often necessary . The aim of this study was to compare the effects of orlistat and placebo on body weight , glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes . METHODS Two hundred and fifty-four obese , diabetic patients were enrolled in this study and r and omized to take orlistat 360 mg or placebo for 1year . We evaluated at baseline and after 3 , 6 , 9 and 12months body weight , waist circumference ( WC ) , body mass index ( BMI ) , glycated haemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , lipid profile , retinol-binding protein-4 ( RBP-4 ) , resistin , visfatin and high-sensitivity C-reactive protein ( Hs-CRP ) . RESULTS AND DISCUSSION We observed a significant reduction in body weight , WC , BMI , lipid profile , RBP-4 and visfatin in the orlistat group but not in control group . Faster improvements in HbA(1c ) , PPG , FPI , HOMA-IR , resistin and Hs-CRP were recorded with orlistat than with placebo . A similar decrease in FPG was seen in the two groups . Significant predictors of change in insulin resistance ( HOMA-IR ) were RBP-4 and resistin concentration in the orlistat group ( r=-0·53 , P<0·05 , and r=-0·59 , P<0·01 , respectively ) . WHAT IS NEW AND CONCLUSION To the best of our knowledge , this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation . Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control , without any serious adverse event . Orlistat also improved RBP-4 and visfatin , effects not observed with placebo
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 .