Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. Addition of orlistat to conventional treatment in adolescents with severe obesity. Treatment of obese adolescents with sibutramine: a randomized, double-blind, controlled study. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. Effects of sibutramine treatment in obese adolescents: a randomized trial. The effect of sibutramine on energy expenditure and body composition in obese adolescents. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Orlistat in the long-term treatment of obesity in primary care settings. A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.
Adolescent obesity is becoming a national public health problem. Weight-loss medications including sibutramine facilitate weight control in adults and could be used with obese adolescents in combination with behavior therapy (BT).
                To examine whether increased weight loss in obese adolescents is induced when sibutramine is added to a family-based, behavioral weight control program.
                Randomized, double-blind, placebo-controlled trial consisting of 82 adolescents aged 13 to 17 years with a body mass index (BMI) of 32 to 44 conducted from March 1999 to August 2002 at a university-based clinic for 6 months, followed by open-label treatment during months 7 to 12.
                For the first 6 months, participants received either BT and sibutramine or BT and placebo. From months 7 to 12, all participants received sibutramine in open-label treatment.
                Percentage change in BMI; systolic and diastolic blood pressure and pulse; and hunger.
                In intention-to-treat analysis at month 6, participants in the BT and sibutramine group lost a mean (SD) of 7.8 kg (6.3 kg) and had an 8.5% (6.8%) reduction in BMI, which was significantly more than weight loss of 3.2 kg (6.1 kg) and reduction in BMI of 4.0% (5.4%) in the BT and placebo group. Significantly greater reductions in hunger (P =.002) also were reported by participants who received BT and sibutramine. From months 7 to 12, adolescents initially treated with sibutramine gained 0.8 kg (10.5 kg) with continued use of the medication, whereas those who switched from placebo to sibutramine lost an additional 1.3 kg (5.4 kg). Medication dose was reduced (n = 23) or discontinued (n = 10) to manage increases in blood pressure, pulse rate, or other symptoms.
                The addition of sibutramine to a comprehensive behavioral program induced significantly more weight loss than did BT and placebo. Until more extensive safety and efficacy data are available, medications for weight loss should be used only on an experimental basis in adolescents and children. 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 obesity is becoming a health problem in both developed and developing countries. Antiobesity drug therapy is not currently indicated for the treatment of adolescent obesity and remains investigational at this time. The aim of this study was to determine the efficacy and safety of sibutramine in obese adolescents. A randomized, double-blind, placebo-controlled trial, enrolling 60 adolescents, aged 14-17 yr, for 6 months was conducted. In the first month, all patients received placebo and a hypocaloric diet plus exercise orientation. For the next 6 months, participants received either sibutramine or placebo. Patients assigned to sibutramine group lost an average of 10.3 +/- 6.6 kg, and patients in placebo group lost 2.4 +/- 2.5 kg (P < 0.001). The mean body mass index reduction was significantly greater in the sibutramine group (3.6 +/- 2.5 kg/m(2)) than in the placebo group (0.9 +/- 0.9 kg/m(2); P < 0.001). No participant withdrew because of adverse events, and no difference in blood pressure or heart rate was noted between groups. There were no changes in echocardiographic parameters. In conclusion, sibutramine plus diet and exercise induced significantly more weight loss in obese adolescents. The prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weight reduction, and pharmacological treatment has not been extensively studied.
                To determine the efficacy and safety of orlistat in weight management of adolescents.
                Multicenter, 54-week (August 2000-October 2002), randomized, double-blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI] >or=2 units above the 95th percentile) at 32 centers in the United States and Canada.
                A 120-mg dose of orlistat (n = 357) or placebo (n = 182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy.
                Change in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge.
                There was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5% and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (-1.33 cm vs +0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group.
                In combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group. Increased prevalence of adolescent obesity requires effective treatment options beyond behavior therapy.
                To see whether sibutramine reduced weight more than placebo in obese adolescents who were receiving a behavior therapy program.
                12-month, 3:1 randomized, double-blind trial conducted from July 2000 to February 2002.
                33 U.S. outpatient clinics.
                498 participants 12 to 16 years of age with a body mass index (BMI) that was at least 2 units more than the U.S. weighted mean of the 95th percentile based on age and sex, to the upper limit of 44 kg/m2. Interventions: Site-specific behavior therapy plus 10 mg of sibutramine or placebo. Blinded study medication dose was uptitrated to 15 mg or placebo at month 6 if initial BMI was not reduced by 10%.
                Body mass index, waist circumference, body weight, fasting lipid and glycemic variables, safety, and tolerability.
                Seventy-six percent of patients in the sibutramine group and 62% of patients in the placebo group completed the study. The estimated mean treatment group difference at month 12 (linear mixed-effects model) favored sibutramine for change from baseline in BMI (-2.9 kg/m2 [95% CI, -3.5 to -2.2 kg/m2]) and body weight (-8.4 kg [CI, -9.7 to -7.2 kg]) (P < 0.001 for both). The sibutramine group had greater improvements in triglyceride levels, high-density lipoprotein cholesterol levels, insulin levels, and insulin sensitivity (P < or = 0.001 for all). The rate of tachycardia was greater with sibutramine vs. placebo (12.5% vs. 6.2%; difference, 6.3 percentage points [CI, 1.0 to 11.7 percentage points]) but did not lead to increased withdrawal (2.4% vs. 1.5%; difference, 0.9 percentage point [CI, -1.7 to 3.5 percentage points]).
                The 1-year study duration precluded assessment of long-term weight maintenance and putative health benefits and harms, and 24% and 38% of the sibutramine and placebo groups, respectively, did not complete follow-up.
                Sibutramine added to a behavior therapy program reduced BMI and body weight more than placebo and improved the profile of several metabolic risk factors in obese adolescents. Childhood obesity is now considered to be an epidemic. Drug therapy in this age group remains a topic of research.
                The objective of this study was to examine the effect of treatment with sibutramine (10 mg) on body composition and energy expenditure in obese adolescents.
                The study was conducted as a randomized, double-blind, placebo-controlled trial.
                The study was set in an obesity research center.
                The patients were 24 obese adolescents (age 12-17 yr, 11 boys); four patients withdrew.
                Intervention was sibutramine (Meridia) or placebo in combination with an energy-restricted diet and exercise plan for 12 wk, followed by an identical, but medication-free, treatment period (follow-up).
                Change in body mass index (BMI) sd score (BMI-SDS) was the principal measure of efficacy. Body composition and total energy expenditure were measured by stable isotopes and further calculated according to the four-component model, using underwater weighing and dual x-ray absorptiometry. Basal metabolic rate (BMR) was measured by ventilated hood and adjusted for sex and body composition (BMRadj).
                After intervention, the decrease in BMI-SDS was comparable in both groups. During follow-up, BMI further decreased in the placebo group but stabilized in the sibutramine group. Changes in the percentage of fat mass were not different between both groups. BMRadj decreased in the placebo group and remained constant in the sibutramine group. During follow-up, BMRadj decreased in the sibutramine group and increased in the placebo group. Changes in total energy expenditure were not significantly different.
                The effect of sibutramine on BMI-SDS was not significant. Sibutramine may diminish the decrease in BMRadj associated with energy restriction in obese adolescents. 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.
                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.
                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.
                Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life. To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity.
                Randomized, double-blind, placebo-controlled, multicenter study.
                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.
                Seventeen primary care centers in the United States.
                Changes in body weight and obesity-related disease risk factors.
                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.
                This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings. Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder.
                Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification.
                The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group.
                Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.
While there is limited quality data to recommend one treatment program to be favoured over another, this review shows that combined behavioural lifestyle interventions compared to standard care or self-help can produce a significant and clinically meaningful reduction in overweight in children and adolescents. In obese adolescents, consideration should be given to the use of either orlistat or sibutramine, as an adjunct to lifestyle interventions, although this approach needs to be carefully weighed up against the potential for adverse effects. Furthermore, high quality research that considers psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care is required.