Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group

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, randomized, double-blind, placebo-controlled study. Obese patients (body mass index 28 to 43 kg/m2) were randomized 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.     

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.     

Effect of orlistat in obese patients with binge eating disorder

OBJECTIVE: Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder. RESEARCH METHODS AND PROCEDURES: Eighty-nine patients with clinically diagnosed binge eating disorder and a BMI > or = 30 kg/m2 were randomized in double-blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced-calorie diet. RESULTS: After 24 weeks, the mean weight loss from baseline for orlistat-treated patients was significantly greater than for patients receiving placebo (-7.4% vs. -2.3%; p = 0.0001) (intent-to-treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011). DISCUSSION: Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.     

Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain

BACKGROUND: Conjugated linoleic acid (CLA) is marketed as a safe, simple, and effective dietary supplement to promote the loss of body fat and weight. However, most previous studies have been of short duration and inconclusive, and some recent studies have questioned the safety of long-term supplementation with CLA. OBJECTIVE: Our aim was to assess the effect of 1-y supplementation with CLA (3.4 g/d) on body weight and body fat regain in moderately obese people. DESIGN: One hundred twenty-two obese healthy subjects with a body mass index (in kg/m2) > 28 underwent an 8-wk dietary run-in with energy restriction (3300-4200 kJ/d). One hundred one subjects who lost >8% of their initial body weight were subsequently randomly assigned to a 1-y double-blind CLA (3.4 g/d; n = 51) or placebo (olive oil; n = 50) supplementation regime in combination with a modest hypocaloric diet of -1250 kJ/d. The effects of treatment on body composition and safety were assessed with the use of dual-energy X-ray absorptiometry and with blood samples and the incidence of adverse events, respectively. RESULTS: After 1 y, no significant difference in body weight or body fat regain was observed between the treatments. The CLA group (n = 40) regained a mean (+/-SD) 4.0 +/- 5.6 kg body weight and 2.1 +/- 5.0 kg fat mass compared with a regain of 4.0 +/- 5.0 kg body weight and 2.7 +/- 4.9 kg fat mass in the placebo group (n = 43). No significant differences in reported adverse effects or indexes of insulin resistance were observed, but a significant increase in the number of leukocytes was observed with CLA supplementation. CONCLUSION: A 3.4-g daily CLA supplementation for 1 y does not prevent weight or fat mass regain in a healthy obese population.     

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.     

A 6-month randomized,placebo-controlled,dose-ranging trial of topiramate for weight loss in obesity

OBJECTIVE: To evaluate the efficacy and safety of topiramate (TPM) for weight loss in healthy obese subjects. RESEARCH METHODS AND PROCEDURES: A randomized, double-blind, placebo-controlled, dose-ranging trial was conducted. Three hundred eighty-five subjects, 18 and 75 years of age, were randomized to receive either placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily. In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was raised every week by 32 mg/d (16 mg twice daily) until subjects reached their target dose. Twenty-four weeks after beginning treatment, all subjects were tapered off treatment by a dose reduction of 50% per week. All participants received the same lifestyle program. RESULTS: Mean percent weight loss from baseline to week 24 was -2.6% in placebo-treated patients vs. -5.0%, -4.8%, -6.3%, and -6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively. Greater percentages of TPM-treated patients lost at least 5% or 10% of body weight compared with placebo. The most frequent adverse events were related to the central or peripheral nervous system, including paresthesia, somnolence, and difficulty with memory, concentration, and attention. Most events were dose-related, occurred early in treatment, and usually resolved spontaneously; only 21% receiving TPM withdrew due to adverse events compared with 11% on placebo. DISCUSSION: TPM produced significantly greater weight loss than placebo at all doses.     

Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects

The aim of the present study was to investigate whether capsaicin assists weight maintenance by limiting weight regain after weight loss of 5 to 10 %. In this randomized double-blind placebo-controlled study, ninety-one moderately overweight subjects were randomly assigned to an intensive group that underwent all the measurements, and an extensive group that underwent the same measurements except the metabolism measurements. After a 4-week very-low-energy diet (VLED) intervention, a 3-month weight-maintenance period followed. During weight maintenance, subjects were divided into a capsaicin (135 mg capsaicin/d) and a placebo group. Body mass was measured before and after the VLED and after 1, 2 and 3 months of weight maintenance. The mean body-mass loss during the VLED was 6.6 (SD 2.0) kg (7.8 (SD 1.8) % initial body mass), and was not different between the subsequent treatment and placebo group. During weight maintenance, mean % regain during treatment was not significantly different compared with placebo (33.3 (SD 35.7) v. 19.2 (SD 41.8) %, P=0.09). RQ was significantly less increased during weight maintenance in the treatment group compared with placebo (0.04 (SD 0.06) v. 0.07 (SD 0.05), P<0.05), indicating a relatively more sustained fat oxidation. Fat oxidation (g/h) after weight maintenance was higher in the capsaicin group compared with placebo (4.2 (SD 1.1) v. 3.5 (SD 0.9), P<0.05). These results indicate that capsaicin treatment caused sustained fat oxidation during weight maintenance compared with placebo. However, capsaicin treatment has no limiting effect on 3-month weight regain after modest weight loss.     

Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women

BACKGROUND: Dietary fat has been reported to influence insulin sensitivity. OBJECTIVE: The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity. DESIGN: Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss. RESULTS: The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group. CONCLUSIONS: Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.     

Effects of green tea on weight maintenance after body-weight loss

The present study was conducted to investigate whether green tea may improve weight maintenance by preventing or limiting weight regain after weight loss of 5 to 10 % in overweight and moderately obese subjects. The study had a randomised, parallel, placebo-controlled design. A total of 104 overweight and moderately obese male and female subjects (age 18-60 years; BMI 25-35 kg/m(2)) participated. The study consisted of a very-low-energy diet intervention (VLED; 2.1 MJ/d) of 4 weeks followed by a weight-maintenance period of 13 weeks in which the subjects received green tea or placebo. The green tea contained caffeine (104 mg/d) and catechins (573 mg/d, of which 323 mg was epigallocatechin gallate). Subjects lost 6.4 (sd 1.9) kg or 7.5 (sd 2.2) % of their original body weight during the VLED (P<0.001). Body-weight regain was not significantly different between the green tea and the placebo group (30.5 (sd 61.8) % and 19.7 (sd 56.9) %, respectively). In the green tea treatment, habitual high caffeine consumption was associated with a higher weight regain compared with habitual low caffeine consumption (39 (sd 17) and 16 (sd 11) %, respectively; P<0.05). We conclude that weight maintenance after 7.5 % body-weight loss was not affected by green tea treatment and that habitual caffeine consumption affected weight maintenance in the green tea treatment.     

Efficacy of orlistat 60 mg on weight loss and body fat mass in US Army soldiers

A higher body mass index is associated with exercise-related injuries and increased risk for musculoskeletal and connective tissue disorders, which are relevant to military personnel. Studies show the efficacy of orlistat 60 mg for promoting weight and body fat loss in civilians; however, its efficacy among predominantly young, male soldiers is unknown. This study's objective was to examine the effect of a 6-month, standard education-based weight-management program with and without orlistat 60 mg on changes in weight and body fat in overweight soldiers. Data were collected for this randomized, controlled trial from March 2008 to November 2010 at Fort Bragg, NC. Participants were enrolled in an education-based weight management program (n=435; 75% men) and were randomized to placebo or orlistat 60 mg, three capsules daily with meals. All participants were recommended to maintain a reduced-energy, low-fat diet. Among study completers (14% retention rate; placebo n=22, orlistat n=35) members of both groups lost significant weight from baseline (placebo ?3.0±5.2 kg; orlistat ?3.2±4.7 kg; P<0.01), but only the orlistat group lost fat mass (?2.5±3.9 kg; P<0.001), whereas the placebo group lost lean mass (?1.4±2.7 kg; P <0.01). An intent-to-treat analysis (≥1 follow-up body weight measure) demonstrated that the orlistat group lost more fat mass vs the placebo group (?1.3±2.9 kg vs ?0.6±1.8 kg, respectively; P<0.05), but less lean mass (?0.2±2.0 kg vs ?0.8±1.8 kg, respectively; P<0.01). Orlistat 60 mg may be an effective adjunct to an education-based weight management program in a mostly young, male soldier population.     

Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects

OBJECTIVE: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet. RESEARCH METHODS AND PROCEDURES: Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. RESULTS: Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. DISCUSSION: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.     

Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity.

OBJECTIVE: The researchers assessed the long-term weight reduction efficacy, tolerability, and safety of sibutramine used once daily in conjunction with behavior modification to treat mild to moderate obesity. STUDY DESIGN: This was a double-blind randomized placebo-controlled parallel-group comparative study of sibutramine 10 mg or 15 mg (or placebo) once daily for 1 year, given with dietary advice. POPULATION: A total of 485 obese men and women with uncomplicated obesity were included (mean age=42 years, mean body mass index=32.7 kg/m2). OUTCOMES MEASURED: The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects. RESULTS: Among patients completing the study, those taking sibutramine 10 mg or 15 mg had greater mean weight loss compared with placebo at 12-month assessment (P < or = .001). Changes in body weight from baseline to end point were -1.6 kg for those taking placebo, -4.4 kg for those taking sibutramine 10 mg (P < or =.01, last observation carried forward [LOCF]), and -6.4 kg for those taking sibutramine 15 mg (P < or =.001, LOCF). For placebo patients, 20% lost 5% or more of their body weight compared with 39% of patients taking sibutramine 10 mg and 57% taking sibutramine 15 mg. Only 7% of the patients taking placebo lost 10% or more of their body weight, compared with 19% taking sibutramine 10 mg and 34% taking sibutramine 15 mg (P <.001 for both 10 mg and 15 mg vs placebo, and for both > or =5% and > or =10%). CONCLUSIONS: Sibutramine 10 mg or 15 mg once daily given with dietary advice produces and maintains statistically and clinically significantly greater weight loss than dietary advice alone (placebo) throughout a 12-month treatment period, and is safe and well tolerated.     

Bupropion SR enhances weight loss: a 48-week double-blind,placebo- controlled trial

OBJECTIVE: To critically examine the efficacy of bupropion SR for weight loss. RESEARCH METHODS AND PROCEDURES: This 24-week multicenter, double-blind, placebo-controlled study randomized obese adults to placebo, bupropion SR 300, or 400 mg/d. Subjects were counseled on energy-restricted diets, meal replacements, and exercise. During a 24-week extension, placebo subjects were randomized to bupropion SR 300 or 400 mg/d in a double-blinded manner. RESULTS: Of 327 subjects enrolled, 227 completed 24 weeks; 192 completed 48 weeks. Percentage losses of initial body weight for subjects completing 24 weeks were 5.0%, 7.2%, and 10.1% for placebo, bupropion SR 300, and 400 mg/d, respectively. Compared with placebo, net weight losses were 2.2% (p = 0.0468) and 5.1% (p < 0.0001) for bupropion SR 300 and 400 mg/d, respectively. The percentages of subjects who lost >or=5% of initial body weight were 46%, 59%, and 83% (p vs. placebo < 0.0001) for placebo, bupropion SR 300, and 400 mg/d, respectively; weight losses of >or=10% were 20%, 33%, and 46% (p vs. placebo = 0.0008) for placebo, bupropion SR 300, and 400 mg/d, respectively. Withdrawals, changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks. Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5% and 8.6% for bupropion SR 300 and 400 mg/d, respectively. DISCUSSION: Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.     

Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials

BACKGROUND: Obesity is a growing health concern in Canada and the United States, and pharmacologic therapies such as orlistat are being more commonly prescribed to assist with weight loss. OBJECTIVE: Our goal was to assess the efficacy and safety of orlistat compared with either placebo or an active control with regard to weight loss and serum lipid changes in overweight patients. DESIGN: We performed a systematic literature search of MEDLINE (1966 through December 2003) and the Cochrane Central Register of Controlled Trials. Relevant trials and reviews were searched by hand. Randomized trials comparing orlistat and a control and reporting changes in weight loss, serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol, LDL:HDL, and triacylglycerols), or both in overweight and obese patients [body mass index (in kg/m2) > or =25] were included. RESULTS: Twenty-eight randomized trials met our inclusion criteria. Seventeen studies including 10,041 patients compared 3 x 120 mg orlistat/d with placebo or an inactive control along with a hypocaloric diet over a 1-y period. Relative risks (RRs) associated with clinically significant weight losses of 5% and 10% were 1.74 (95% CI: 1.57, 1.91) and 1.96 (1.74, 2.21), both favoring orlistat. Improvement in total cholesterol, LDL cholesterol, HDL cholesterol, and LDL:HDL were also greater with orlistat. Gastrointestinal events were more common with orlistat than with placebo [RR: 1.46 (1.37, 1.55)]. CONCLUSION: Our findings suggest that 3 x 120 mg orlistat/d is effective for improving both weight loss and serum lipid profiles in obese patients at low and high cardiovascular disease risk and in obese patients with type 2 diabetes.     

Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition

OBJECTIVE: To evaluate the effect of a dietary supplement containing herbal caffeine (70 mg/dose) and ephedra (24 mg/dose; C&E) on metabolic rate, weight loss, body composition, and safety parameters. RESEARCH METHODS AND PROCEDURES: In phase I, 12 healthy subjects with a BMI of 25 to 35 kg/m2 had resting metabolic rate (RMR) measured for 2 hours after ingesting C&E or a placebo on two occasions 1 week apart, followed by a 1-week washout before phase II. In phase II, these 12 and 28 additional subjects were randomized to a 12-week, double-blind trial comparing C&E (3 times/day) to placebo. In phase III, the C&E group was given open-label C&E for 3 months, and the placebo group was given C&E for 6 months. RESULTS: In phase I, C&E gave an average 8 +/- 0.1% (SE) rise in RMR over 2 hours compared with placebo (p < 0.01). In phase II, weight loss at 12 weeks was 3.5 +/- 0.6 kg with C&E compared with 0.8 +/- 0.5 kg with placebo (p < 0.02). The percentage fat lost, shown by DXA, was 7.9 +/- 2.9% with C&E and 1.9 +/- 1.1% with placebo (p < 0.05). Pulse decreased more in the placebo group that in the C&E group (p < 0.03). There were no differences in lipid levels or blood pressure. In phase III, there was a 6-month loss of 7.3% and 7.8% of initial body weight for the groups on placebo and C&E during phase II, respectively. There were no serious adverse events. DISCUSSION: C&E increased RMR significantly by 8% compared with placebo, promoted more weight and fat loss than placebo, and was well tolerated.     

Fluoxetine: a randomized clinical trial in the maintenance of weight loss

Because current weight-reduction treatments have considerable recidivism, a therapy that could help patients maintain weight loss would be of benefit. A six-center, randomized, double-blind trial compared the effects of the specific serotonin uptake inhibitor, fluoxetine hydrochloride, and placebo on maintenance of weight loss. Obese outpatients who had lost > or = 3.6 kg after 8 weeks of single-blind fluoxetine 60 mg/day in the qualification phase (N=317 [70.4% of patients entered]; mean +/- standard deviation [SD] weight loss, 6.8 +/- 2.8 kg) were randomly assigned to fluoxetine 20 mg/day (N=104), fluoxetine 60 mg/day (N=106), or placebo (N=107) for 40 weeks (maintenance phase). Patients received minimal nutrition/dietary counseling. Qualification phase clinic visits were biweekly; maintenance phase visits were monthly for 4 months, then bimonthly for 6 months. Patients treated with fluoxetine 60 mg/day continued to lose weight for 8 additional weeks (16 weeks total; maximum mean +/- SD weight loss, 7.2 +/- 4.6 kg); those treated with fluoxetine 20 mg/day or placebo began to regain weight. Mean weights remained below baseline values at week 48 (all groups); treatment differences were not statistically significant. Study completion rates were comparable (fluoxetine 20 mg/day, 67.3%; fluoxetine 60 mg/day, 56.6%; placebo, 67.3%; p = 0.175). Among commonly reported adverse events (> 10% incidence), only asthenia was reported statistically significantly (p < 0.050) more frequently with fluoxetine than with placebo. Few patients discontinued for any single adverse event. Fluoxetine 60 mg/day was effective for a longer period than fluoxetine 20 mg/day or placebo in maintaining weight loss. Overall, fluoxetine was safe and well tolerated.     

Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial

OBJECTIVE: This study assessed whether adding orlistat to sibutramine would induce further weight loss in patients who previously had lost weight while taking sibutramine alone. RESEARCH METHODS AND PROCEDURES: Patients were 34 women with a mean age of 44.1 +/- 10.4 years, weight of 89.4 +/- 13.8 kg, and body mass index (BMI) of 33.9 +/- 4.9 kg/m2 who had lost an average of 11.6 +/- 9.2% of initial weight during the prior 1 year of treatment by sibutramine combined with lifestyle modification. Patients were randomly assigned, in double-blind fashion, to sibutramine plus orlistat or sibutramine plus placebo. In addition to medication, participants were provided five brief lifestyle modification visits during the 16-week continuation trial. RESULTS: Mean body weight did not change significantly in either treatment condition during the 16 weeks. The addition of orlistat to sibutramine did not induce further weight loss as compared with treatment by sibutramine alone (mean changes = +0.1 +/- 4.1 kg vs. +0.5 +/- 2.1 kg, respectively). DISCUSSION: These results must be interpreted with caution because of the study's small sample size. The findings, however, suggest that the combination of sibutramine and orlistat is unlikely to have additive effects that will yield mean losses > or =15% of initial weight, as desired by many obese individuals.     

Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects

OBJECTIVE: To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects on body-weight maintenance, parameters of appetite and energy intake (EI) at breakfast after weight loss. DESIGN: This study had a double-blind, placebo-controlled randomized design. SUBJECTS: A total of 26 men and 28 women (age 37.8+/-7.7 y; body mass index 27.8+/-1.5 kg/m(2)). INTERVENTIONS: Subjects were first submitted to a very-low-calorie diet (VLCD; 2.1 MJ/day) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day or 3.6 g CLA or placebo per day. Additionally, subjects of the high dosage intervention replaced their habitual lunch by one meal of a protein-rich, low-energy supplement. EI was measured at breakfast and appetite profile after an overnight fast. RESULTS: The mean body weight loss was 6.9+/-1.7% of their original body weight. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not have an effect on body weight regain. Feelings of fullness and satiety were increased and feelings of hunger were decreased after 13 weeks intervention by CLA compared to placebo, independent of %body weight regain. However, EI measured at breakfast was not affected by CLA. CONCLUSION: Appetite (hunger, satiety and fullness) was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day. This did not result in a lower EI at breakfast or an improved body-weight maintenance after weight loss.     

The long-term influence of orlistat on dietary intake in obese subjects with components of metabolic syndrome

Background:  Orlistat is a lipase inhibitor that reduces the intestinal absorption of fat and may enhance the effects of dietary and behavioural therapy on weight loss and maintenance. The present study examined the effect of orlistat on dietary intake, especially fat intake, during long-term weight maintenance.
Methods:  Subjects comprised 44 men and women (aged 18–63 years; body mass index 37.5 ± 4.3 kg m⁻²) included in the Scandinavian Multicenter study of Obese subjects with the metabolic syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week, very low energy diet (VLED). Two months after the end of the trial when the use of orlistat was optional, 33 subjects remained in the study. A dietary interview based on a validated food frequency questionnaire was conducted before the VLED, after 1 year of treatment with orlistat or placebo and 2 months after the end of the trial.
Results:  At 1 year, dietary intake did not differ between the orlistat and placebo group. Energy percent (E%) fat was reduced and E% carbohydrate was increased within both groups. Two months after the end of the trial, E% fat was 32.6% (SD 6.2%) in subjects that chose to take orlistat and 27.7% (SD 5.5%) in subjects not taking orlistat [between group difference −5.0% (95% confidence interval −9.2 to −0.7); P  = 0.021].
Conclusions:  The use of orlistat compared with placebo in a lifestyle modification programme does not appear to influence dietary intake. Subjects that chose to take orlistat after the end of the programme did not comply with dietary recommendations and this may hamper the effect of the drug.     

Comparative evaluation of fecal fat excretion induced by orlistat and chitosan

OBJECTIVE: To compare the effects of chitosan and orlistat on fecal fat excretion. RESEARCH METHODS AND PROCEDURE: A randomized, open-label, two-period sequential design study was used. A total of 12 healthy adult volunteers within 20% of their ideal body weight entered a 7-day run-in diet period before being randomized to orlistat (120 mg) or chitosan (890 mg) three times daily for 7 days. Subjects then crossed over treatment regimens for an additional 7-day period. Subjects followed a standardized diet (2500 kcal/d, 30% as fat) for the entire 21-day study. Feces were collected on days 4 to 7 of the run-in period (baseline) and during the two treatment periods. Mean daily fecal fat excretion was measured at baseline and during each treatment regimen. RESULTS: Mean baseline fecal fat excretion for all subjects was 1.36 +/- 0.45 g/d. During orlistat treatment, mean fecal fat excretion significantly increased from baseline (+16.13 +/- 7.27 g/d; p < 0.001). No significant effect was observed with chitosan (+0.27 +/- 1.02 g/d; p = 0.379). Fecal fat excretion was significantly greater with orlistat than with chitosan (p < 0.001; 95% confidence intervals: 11.73; 20.00 g/d). DISCUSSION: This study provides additional evidence of the inhibitory effect of orlistat on dietary fat absorption. Chitosan, however, has no effect on fecal fat excretion.