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PubMed2005

The cost effectiveness of orlistat in a 1-year weight-management programme for treating overweight and obese patients in Sweden : a treatment responder approach.

OBJECTIVE: To calculate the cost effectiveness (from the Swedish healthcare perspective) of orlistat plus diet for an obese and overweight population in a 1-year weight-management responder programme versus a 1-year weight-management programme based on diet only. As a reference, orlistat plus diet and diet only were also compared with a no-diet alternative. METHOD: Costs and effectiveness were calculated in a decision-tree model by means of Monte Carlo simulation. Efficacy was derived from a pooled analysis of the orlistat clinical trial programme. Acquisition costs for orlistat (euro, 2003 prices), healthcare costs for visits to doctors and dieticians related to weight management, and costs related to the difference in diabetes mellitus incidence between treatment arms were included in the analysis. The health benefit of temporary weight loss was measured in the number of quality-adjusted life-years (QALYs) gained. RESULTS: The number of responding (those with >5% weight loss) patients at month 3 was almost twice as high with orlistat compared with diet only: 48.9% versus 26.3%. Responding orlistat patients had a weight loss of 15.5% at month 12 compared with 7.9% for all patients on diet only. The incremental cost-effectiveness ratio (ICER) per QALY gained versus diet only was estimated to be 13,125 euro for the average patient starting on orlistat. When orlistat was compared with no diet, the cost effectiveness was improved. However, comparing diet only with no diet gave a slightly higher ICER, indicating that orlistat had an extended dominance over the diet-only alternative. CONCLUSION: Our estimates indicated that orlistat in a 12-month dietary responder programme increased the number of QALYs and reduced the cumulative incidence of diabetes compared with diet only. Patients starting on orlistat in addition to a dietary programme achieved an ICER that was similar to many other well accepted healthcare treatment programmes. In order to improve the precision of our calculations, we need to confirm the key assumptions regarding temporary weight loss and utility gains, and the relationship between temporary weight loss and diabetes, as well as other co-morbidities, and to have better knowledge of the long-term impact of weight-management programmes in clinical practice, such as changes in weight-controlling behaviours and sustainability of weight loss.

Adult↗
PubMed2004

Comparison of metabolic effects of orlistat and sibutramine treatment in Type 2 diabetic obese patients.

AIM: The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese diabetic patients of both sexes, with specific attention to metabolic pattern-induced changes and cardiovascular effects. METHODS: Patients were enrolled, evaluated, and followed in 3 Italian Centres of Internal Medicine. We evaluated 144 obese diabetic patients. All were required to have been diagnosed as being diabetic for at least 6 months, and had glycaemic control with diet alone or diet and oral hypoglycaemic agents. We administered orlistat (360 mg/d) or sibutramine (10 mg/d) in a randomized, controlled, double-blind clinical study, and evaluated anthropometric variables, glycaemic control, blood pressure and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 141 (69 males and 72 females; 35 males and 36 females, aged 53 +/- 5 yr with orlistat; 34 males and 36 females, aged 51 +/- 4 yr with sibutramine) completed the 4 weeks on controlled-energy diet and were randomized to double-blind treatment with orlistat (n=71) or sibutramine (n=70). Significant body mass index (BMI) improvement was present after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in both groups. Significant waist circumference (WC), hip circumference (HC), and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p<0.05, respectively) in both groups. Significant HbA1c decrease was obtained after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) levels were significantly decreased in both groups (p<0.05 andp<0.02, respectively). Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p<0.05) was present in the orlistat group after 12 months. No significant change in blood pressure measurements was observed in the sibutramine group during the study. No significant HR variation was obtained during the study in either group. Of the 133 patients who completed the study, 33.8% of patients in the orlistat group and 13.2% of patients in the sibutramine group had side effects (p<0.05 vs orlistat group). Side effect profiles were different in the two treatmen groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pres sure (both SBP and DBP) in one patient, but it was controlled by anti-hypertensive treatment. The vita min changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation. CONCLUSIONS: Both orlistat and sibutramine were effective on anthropometric variables and on metabolic pattern during the 12-month treatment; in our sample, orlistat appears to be slightly more efficacious as an anti-obesity drug, while sibutramine intake was not associated to any cardiovascular effect and was generally better tolerated than orlistat.

Anthropometry↗
PubMed2002

Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension.

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, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives. INTERVENTIONS: Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed. 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 > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04). CONCLUSION: A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction.

Anti-Obesity Agents↗
PubMed2000

[Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients].

BACKGROUND: We undertook a randomised 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 randomisation 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 clinically 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.

Adolescent↗
PubMed2004

Addition of orlistat to conventional treatment in adolescents with severe obesity.

UNLABELLED: To investigate the efficacy and tolerability of orlistat in obese adolescents, a prospective, open-label, randomised, controlled pilot trial was performed. A total of 22 adolescents with exogeneous obesity were started on orlistat (120 mg tid) and a daily multivitamin preparation in addition to conventional treatment which included nutritional and lifestyle modification programmes. The control group consisted of 20 obese adolescents who had similar duration of follow-up under conventional treatment alone. Of the 22 patients, 7 dropped out within the 1st month of the trial due to side-effects attributable to orlistat. The remaining 15 patients on orlistat were followed for 5-15 months (average duration of treatment 11.7 +/- 3.7 months). The control group was similar in age, sex, and duration of follow-up (10.2 +/- 3.7 months, range 6-17 months) to the orlistat group. Compared to initial body weight, patients in the orlistat group lost -6.27 +/- 5.4 kg, whereas those in the control group gained 4.16 +/- 6.45 kg (P < 0.001) during the study period. Patients in the orlistat group lost -7.65% +/- 6.5% of their initial body weight, whereas, those of the control group gained 5.7% +/- 8.3% (P < 0.001). The body mass index decreased in the orlistat group by -4.09 +/- 2.9 kg/m2 while it increased by + 0.11 +/- 2.49 kg/m2 in the control group (P < 0.001). Mild gastrointestinal complaints (frequent stools) were experienced by all patients in the orlistat group. CONCLUSION: Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents; however, gastrointestinal side-effects limit its usefulness in almost one in three adolescents.

Adolescent↗
PubMed2001

Short-term orlistat treatment does not affect mineral balance and bone turnover in obese men.

Orlistat is a gastrointestinal lipase inhibitor that is used to reduce dietary fat absorption and to enhance weight loss in subjects consuming a hypocaloric diet. To assess whether orlistat has an effect on the metabolism of six minerals, a 21-d, double-blind, randomized, parallel-group, placebo-controlled mineral balance study was conducted in obese (body mass index > 30 kg/m(2)) men. Subjects consumed a hypocaloric diet with a constant daily mineral content and received daily oral treatment with orlistat (120 mg three times daily) (n = 14) or placebo (three times daily) (n = 14) for 21 d. After a 14-d equilibration period, calcium, phosphorus, magnesium, iron, copper and zinc balances were assessed for d 15-21. In addition, the effect of diet and orlistat treatment on bone metabolism was estimated from measurement of biomarkers of bone formation and bone resorption. Serum and urine electrolytes were also measured at baseline and at the end of treatment. Orlistat inhibited fat absorption by approximately 33% (P < 0.05). There were no significant differences in mineral apparent absorption, urinary mineral loss or mineral balance between the orlistat and placebo groups. Markers of bone turnover and serum and urine electrolytes did not differ between the orlistat and placebo groups. Orlistat was well tolerated; adverse events were of mild or moderate intensity, and the majority of these events were unrelated or remotely related to study treatment. In obese men consuming a hypocaloric diet, the administration of orlistat had no significant effect on the balance of six selected minerals. In addition, biomarkers of bone turnover, as well as serum and urine electrolytes, were not affected by orlistat treatment.

Adult↗
PubMed2005

Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes.

AIMS: Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks' treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes. METHODS: A total of 249 Chinese patients (body mass index 25-40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n=124) or orlistat 120 mg (n=125) three times daily; all patients followed a mildly reduced-calorie diet. Patients had HbA1c 6.5-8.5% (mean 7.3%) and had never received any glucose-lowering medication. RESULTS: Orlistat-treated patients achieved significantly greater weight loss at the study end than placebo-treated patients (-5.4 vs. -2.4 kg; P<0.0001). More orlistat than placebo patients lost>or=5% (60.5 vs. 26.8%; P<0.0001) and >or=10% of their body weight (20.2 vs. 4.9%; P=0.0002). A significantly greater decrease in HbA(1c) from baseline was obtained with orlistat than placebo (-1.0 vs. -0.6%; P=0.0008). Orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P=0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P<0.0001) than placebo recipients. Also, more orlistat- than placebo-treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P=0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference. CONCLUSIONS: In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.

Adolescent↗
PubMed2001

Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss.

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 randomized 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 designed 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.

Adult↗
PubMed2001

Orlistat--a novel weight loss therapy.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of obesity. DATA SOURCES: English-language articles were identified from MEDLINE (1966-July 2000), Roche Laboratories, organizational guidelines, National Institutes of Health and Food and Drug Administration Web sites, and Doctor's Guide online. Key words included obesity, orlistat, and lipase inhibitors. References were also identified from reference sections of published articles. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled, human trials were selected for review and discussion. DATA SYNTHESIS: Orlistat is the first agent in the lipase inhibitor class of antiobesity drugs. Orlistat is minimally absorbed and has been shown to reduce body weight by inhibiting absorption (by approximately 30%) of ingested dietary fat. Safety and efficacy have been established in one- and two-year double-blind, placebo-controlled trials; adverse effects were primarily, and almost exclusively, gastrointestinal. Due to its ability to block fat absorption, orlistat also has the capability to inhibit absorption of fat-soluble vitamins. Therefore, a daily multiple vitamin is recommended while taking orlistat. CONCLUSIONS: By inhibiting fat absorption, orlistat offers a new treatment modality for weight loss and maintenance. Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia. However, further studies during postmarketing surveillance are needed to fully establish orlistats long-term benefits and safety. Orlistat should be considered a useful adjunctive therapy for weight loss and maintenance in obese patients (i.e., body mass index > or = 30 kg/m2 or > or = 27 kg/m2 if other risk factors are present) committed to lifestyle changes including diet, exercise, and behavioral modification.

Animals↗
PubMed2000

Orlistat: selective inhibition of caloric absorption can affect long-term body weight.

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

Anti-Obesity Agents↗
PubMed1999

Orlistat: a review of its use in the management of obesity.

UNLABELLED: Orlistat is a novel non-systemic treatment for obesity. The drug inhibits lipases in the gastrointestinal tract, preventing the absorption of approximately 30% of dietary fat. Pharmacodynamic and dose-finding studies have established that a 120 mg dose of orlistat 3 times daily (with each main meal) is optimal. Controlled studies have established that orlistat 120 mg 3 times daily for 1 year, in conjunction with a hypocaloric diet, enables weight reduction of 7.9 to 10.2% in obese non-diabetic individuals. In 1 study the reduction was 6.2% in obese patients with type 2 diabetes. Orlistat 120 mg 3 times daily was significantly more effective than placebo (also given in conjunction with a hypocaloric diet) in these studies. The drug was also significantly more effective than placebo in 2-year randomised double-blind studies involving >2000 patients. During the second year of treatment, when patients were switched from a hypocaloric diet to a eucaloric diet, orlistat recipients regained significantly less weight than placebo recipients. Orlistat appears to improve lipid profiles in non-diabetic obese patients, reducing levels of total cholesterol and low density lipoprotein cholesterol. In a study of patients with obesity associated with type 2 diabetes, patients treated with orlistat lost more weight and had improved serum lipid profiles compared with placebo recipients. In addition, orlistat-treated patients achieved significant improvements in glycaemic control, enabling dosages of antidiabetic drugs to be reduced. Long term (1 to 2 years) tolerability data from 2038 patients in placebo-controlled trials revealed that the drug was generally well tolerated. The most commonly reported adverse events were related to decreased fat absorption and included oily faecal spotting, flatus with discharge, faecal urgency and oily stool. Systemic adverse events attributable to orlistat were negligible. CONCLUSION: Orlistat in conjunction with a hypocaloric diet has been shown to induce clinically significant weight loss in keeping with current guidelines for the management of obesity. This, together with its acceptable tolerability profile and lack of systemic adverse events, make it an attractive option in the treatment of obesity. The drug may have a positive effect on obesity-associated cardiovascular risk factors and type 2 diabetes.

Anti-Obesity Agents↗
PubMed1997

A one-year trial to assess the value of orlistat in the management of obesity.

OBJECTIVES: This paper describes the methodology of a multicentre study designed 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, randomized, 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 designed 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 assessments included: measurements of body weight; anthropometry; quality of life; blood pressure; serum lipids; fasting serum glucose and insulin. Safety assessments 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 +/- 5.4kg 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.

Adult↗
PubMed2000

Orlistat in the long-term treatment of obesity in primary care settings.

OBJECTIVE: To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity. DESIGN: Randomized, 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 resulted 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 settings.

Adult↗
PubMed1994

The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia.

The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol > or = 6.2 mmol.l-1 and triglycerides < or = 5.0 mmol.l-1) not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg or 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.

Adult↗
PubMed2003

Effect of orlistat on fat absorption in rats: a comparison of normal rats and rats with diverted bile and pancreatic juice.

Orlistat is a specific inhibitor of pancreatic and gastric lipases leading to decreased absorption of fat. In the present study, we measured the effect of orlistat on lymphatic fat transport in rats following intake of oils very different in FA composition and TAG structure, and compared this with the transport in normal rats and rats with fat malabsorption. Rats were subjected to cannulation of the main mesenteric lymph duct, and a feeding catheter was inserted into the stomach. In addition, malabsorbing rats were cannulated in the common bile and pancreatic duct. Emulsified safflower, fish, and randomized oils were administered, and lymph was collected for 24 h and analyzed for FA composition. Administration of 25 mg orlistat together with the dietary oils resulted in very small changes from baseline lymphatic transport, indicating that inhibition of the fat absorption was almost complete and furthermore that the source of fat had no influence on the inhibitory effect of orlistat. Orlistat did not interfere with the absorption of the hydrolysis products, since high absorption of sn-2 MAG and FFA (oleic acid) mixed with orlistat was observed. The baseline lymphatic transport in the orlistat group was higher than in the malabsorbing group, but this was the result of generally lower transport of endogenous FA in the malabsorbing group, presumably caused by the absence of bile FA. The transport of FA in normal rats was several-fold higher than the transport after orlistat addition and in malabsorbing rats. Thus, this study showed that orlistat inhibited fat hydrolysis, and thereby lymphatic absorption, almost completely independently of the fat administered.

Animals↗
PubMed2006

Safety profile of orlistat: results of a prescription-event monitoring study.

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

Adult↗
PubMed2004

Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity.

BACKGROUND: Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction. AIM: To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation. METHODS: Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months. RESULTS: One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat. CONCLUSIONS: One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.

Adult↗
PubMed2002

The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial.

AIM: To assess the long-term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes. METHODS: This was a multicentre, randomized, placebo-controlled study with a 4-week placebo plus diet lead-in period and a 48-week, double-blind treatment period. Overweight or obese adults [body mass index (BMI) >or= 28 kg/m2] with HbA1c of 6.5-11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low-calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug-naïve). RESULTS: After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (-5.4% vs. -3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of >or= 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo-treated patients in HbA1c (-0.9% vs. -0.4%; p < 0.001), fasting glucose (-1.6 vs.-0.7 mmol/l; p = 0.004) and post-prandial glucose (-1.8 vs. -0.5 mmol/l; p = 0.003). In addition, orlistat-treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat. CONCLUSIONS: Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.

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