Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory to dietary management. A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: a randomized trial. Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. A study of fluoxetine in obese elderly patients with type 2 diabetes. Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Use of sibutramine in overweight adult hispanic patients with type 2 diabetes mellitus: a 12-month, randomized, double-blind, placebo-controlled clinical trial. Weight reduction by sibutramine in obese subjects in primary care medicine: the SAT Study. Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. Weight suppression and weight rebound in ex-smokers treated with fluoxetine. Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy. Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation. A randomized, double-blind study of fluoxetine and maprotiline in the treatment of major depression. Treatment of obese adolescents with sibutramine: a randomized, double-blind, controlled study. Absence of cardiac valve dysfunction in obese patients treated with sibutramine. Fluoxetine treatment of the obese diabetic. Fluoxetine in the treatment of obese type 2 diabetic patients. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes. A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Effects of sibutramine treatment in obese adolescents: a randomized trial. Use of sibutramine in obese mexican adolescents: a 6-month, randomized, double-blind, placebo-controlled, parallel-group trial. Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients. Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients. Treatment effect of sibutramine compared to fluoxetine on leptin levels in polycystic ovary disease. Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Long-term fluoxetine treatment of bulimia nervosa. Fluoxetine Bulimia Nervosa Research Group.
An open, non-comparative study was carried out to assess the efficacy and toleration profile of sibutramine, a new antiobesity drug, in promoting weight loss in obese type 2 diabetes mellitus subject who failed to reduce weight after strict dietary control. Twenty seven patients completed the study. Sibutramine was started as a single morning dose of 10 mg and was subsequently increased to 15 mg daily if weight loss was not satisfactory. The total duration of the study was twelve weeks with followup at every four weeks. Effect of drug was monitored in terms of weight reduction, changes in body mass index, waist circumference, hip circumference, waist/hip ratio and other metabolic parameters. A fixed dietary prescription and concomitant therapy with drugs, if required and not likely to interfere with the trial therapy, was permitted but was not changed during the study period.
                At the end of 12 week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p < 0.001). However, there was no significant change in fasting blood glucose and Hb(A1c) values.
                The study indicates sibutramine to be an effective and well tolerated agent leading to significant reduction in parameter of obesity in obese type 2 diabetic subjects. 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. 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. The purpose of this study was to evaluate the effects of a combination weight loss program using intermittent low-calorie diets, energy-controlled meal replacement products, and sibutramine on weight loss, diabetes control, and cardiovascular risk factors in overweight or obese subjects with type 2 diabetes.
                Overweight or obese individuals with type 2 diabetes treated with diet or oral medication were randomly assigned to either a standard therapy or combination therapy group. Both groups received a standardized program to facilitate weight loss. The combination therapy group also received 10-15 mg sibutramine daily, low-calorie diets using meal replacement products for 1 week every 2 months, and between low-calorie diet weeks, once daily use of meal replacement product and snack bars to replace one usual meal and snack. Primary outcome measures were changes in body weight, glycemic control, plasma lipids, blood pressure, pulse, and body composition at 1 year.
                At 1 year, combination therapy, compared with standard therapy, resulted in significantly more weight loss (-7.3 +/- 1.3 kg vs. -0.8 +/- 0.9 kg, P < 0.001) and reduction in HbA(1c) (-0.6 +/- 0.3 vs. 0.0 +/- 0.2%, P = 0.05). Combination therapy resulted in reduced requirement for diabetes medications and decreased fat mass and lean body mass. A 5-kg decrease in weight at 1 year was associated with a decrease of 0.4% in HbA(1c) (P = 0.006). Changes in fasting glucose, lipids, pulse, and blood pressure did not differ between groups.
                This combination weight loss program resulted in greater weight loss and improved diabetes control compared with a standard weight loss program in overweight or obese subjects with type 2 diabetes. To determine the efficacy and tolerability of sibutramine hydrochloride in obese patients whose type 2 diabetes was poorly controlled on diet alone or with an oral antidiabetic agent.
                This study was a 24-week, double-blind, multicentre trial following a 5-week placebo run-in period. One hundred and seventy-five obese (body mass index (b.m.i.) > or =27 kg/m2) patients with poorly controlled type 2 diabetes mellitus were randomized either to sibutramine (n = 89; mean age 53.5 years; mean weight 99.3 kg) or placebo (n = 86; mean age 55 years; mean weight 98.2 kg) at 16 participating centres. To achieve moderate calorie restriction (deficit > or = 250-500 kcal/day), individual dietary counselling was accompanied by either placebo or sibutramine (initial dosage of 5 mg/day titrated up by 5 mg biweekly through week 6, and maintained at 20 mg through week 24). The main outcome measures included changes in weight, b.m.i., waist and hip circumference, glycaemic control, lipid profile, and quality of life, and evaluation of reported adverse events.
                Sixty-seven per cent of sibutramine patients and 71% of placebo patients completed the study. At week 24 when comparing those who completed the course, sibutramine compared with placebo patients showed significantly greater (p < 0.001) absolute (-4.3 vs. -0.4 kg) and percentage (-4.5% vs. -0.5%) weight loss. Weight loss > or =5% or 10% was achieved by 33% and 8% of sibutramine patients, respectively, but no placebo patients (p < 0.03 or better). Improvement in glycaemic control was correlated with weight loss (p < 0.001). In 5% and 10% weight-loss responders, mean treatment differences were -0.53% and -1.65% (p < or = 0.05), respectively, for HbA1c, and -1.4 mmol/l (p < or =0.05) and -3.8 (p < or =0.05) mmol/l for fasting plasma glucose. Sibutramine patients also showed improvements in fasting insulin, triglycerides, HDL cholesterol, and quality-of-life assessments. Overall, sibutramine was well tolerated compared with the placebo. Sibutramine treatment was associated with small mean increases in blood pressure (BP) and pulse, although an increase in BP was not seen in sibutramine-treated patients who lost > or = 5% of their weight.
                Sibutramine produced statistically and clinically significant weight loss when used in combination with recommendations for moderate caloric restriction. This weight loss was associated with improvements in metabolic control and quality of life, and sibutramine was generally well tolerated in obese patients with type 2 diabetes. In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6-9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects. To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control.
                Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals.
                Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG.
                Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment. Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years.
                Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat.
                148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4.64, p<0.001). Patients had substantial decreases over the first 6 months with respect to triglycerides, VLDL cholesterol, insulin, C peptide, and uric acid; these changes were sustained in the sibutramine group but not the placebo group. HDL cholesterol concentrations rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p<0.001). 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0.1 mm Hg (SD 12.9), diastolic blood pressure by 2.3 mm Hg (9.4), and pulse rate by 4.1 beats/min (11.9).
                This individualised management programme achieved weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for 2 years. Changes in concentrations of HDL cholesterol, VLDL cholesterol, and triglyceride, but not LDL cholesterol, exceed those expected either from weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease. Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits.
                Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo.
                In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01).
                Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year. The management of type 2 diabetes mellitus is complicated by the presence of risk factors related to overweight and obesity, particularly visceral adiposity. However, weight loss and weight maintenance are difficult for patients with diabetes, and the benefits of dietary modifications are typically modest. Sibutramine is a serotonin- and norepinephrine-reuptake inhibitor that reduces food intake by inducing early satiety and attenuates the decrease in basal energy expenditure associated with weight loss. Previous trials of sibutramine in overweight and obese patients with type 2 diabetes have shown significant weight loss accompanied by better glycemic control.
                The goal of this study was to assess the effect on body weight and glycemic control of sibutramine in combination with glibenclamide in obese Hispanic patients with type 2 diabetes.
                This was a 12-month, randomized, double-blind, placebo-controlled clinical trial conducted at the Endocrinology Service, General Hospital of Mexico, Mexico City. Included were overweight or obese (body mass index [BMI] >27 kg/M2) patients with type 2 diabetes between the ages of 24 and 65 years who had been receiving glibenclamide monotherapy for at least 2 weeks and whose glucose concentrations were stable. Patients were randomized to receive sibutramine 10 mg or placebo once daily. The primary efficacy measures were change in body weight, waist circumference, and glycosylated hemoglobin (HbA1c). Anthropometrics and fasting glucose concentrations were measured monthly. HbA1c was determined at baseline and at 6 and 12 months. Laboratory parameters were measured at baseline and at the end of the study.
                Forty-four patients were randomized to receive sibutramine (28 women, 16 men; mean [SD] age, 47.6 [9.0] years), and 42 were randomized to receive placebo (31 women, 11 men; mean age, 45.8 [8.1] years). Twenty-four patients in the sibutramine group and 23 in the placebo group completed the trial. In the sibutramine group, body weight was reduced from a mean (SD) of 73.9 (10.3) kg at baseline to 69.8 (10.6) kg at month 12; BMI decreased from 29.9 (2.6) to 28.2 (2.9) kg/M2; waist circumference was reduced from 94.9 (8.4) to 90.8 (8.4) cm; the plasma fasting glucose concentration decreased from 140.4 (29.4) to 114.2 (32.0) mg/dL; and the HbA1c value was reduced from 8.9% (1.2) to 8.3% (1.2) (all, P < 0.001). In the placebo group, the corresponding changes were from 74.5 (10.3) kg at baseline to 73.1 (11.2) kg at month 12; from 30.1 (2.5) to 29.5 (2.9) kg/M2; from 94.4 (7.3) to 93.1 (8.3) cm (P < 0.05); from 140.7 (25.2) to 123.9 (38.3) mg/dL (P < 0.05); and from 9.0% (1.2) to 9.1% (1.3). In the sibutramine group, weight loss continued for up to 12 months.
                In this population of obese Hispanic patients with type 2 diabetes, sibutramine combined with glibenclamide therapy achieved weight loss for up to 12 months and was associated with better glycemic control than placebo. Sibutramine is a selective serotonin and noradrenaline reuptake inhibitor that is known to reduce body weight. The efficacy of this drug in primary care medicine is currently unknown.
                To study, in a primary healthcare setting, the effect of a standardized non-pharmacological treatment program and 15 mg sibutramine or placebo on long-term weight reduction in obese subjects with a body mass index >or= 30 and < 40 kg/m(2).
                A multicentre, double-blind, placebo-controlled, randomized, parallel group comparison over 54 weeks of continuous therapy.
                33 general practitioners in Germany.
                389 obese patients were recruited of whom 362 were randomized.
                Primary measure was weight reduction at week 54; others included reduction in BMI, waist circumference, waist-hip ratio, blood pressure and blood lipids.
                348 obese subjects were analyzed using an intention-to-treat analysis. Mean weight loss in the sibutramine (S) group was 8.1 +/- 8.2 kg vs. 5.1 +/- 6.5 kg in the placebo (P) group (p < 0.001; Intent-to-treat analysis). More subjects lost more than 5 % and 10 % of initial weight with sibutramine than with placebo (5 %, S: 62.6 %, P: 41.4 %, p < 0.001; 10 %, S: 40.8, P: 19.0 %, p < 0.001). Weight loss was accompanied by an improvement in the lipid profile, in particular, an increase in HDL-cholesterol and a decrease in fasting triglycerides. In both groups, systolic and diastolic blood pressure decreased in those with moderate hypertension and remained unchanged in those with normal blood pressure at baseline. There was a modest increase in heart rate in S (1.9 beats/min) vs. P (- 0.9 beats/min) (p < 0.05).
                Under primary care conditions, sibutramine 15 mg daily proved to be a safe and effective drug for additional weight loss in obese subjects undergoing a comprehensive weight reduction program. 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.
                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.
                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).
                The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects.
                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%).
                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. Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control. Fluoxetine's effect (30 mg, 60 mg, and placebo) on postcessation weight gain was studied among participants from a randomized, double-blind 10-week smoking cessation trial who met strict criteria for abstinence and drug levels. It was hypothesized that (a) fluoxetine would dose-dependently suppress postcessation weight gain and (b) drug discontinuation would produce dose-dependent weight rebound. During the on-drug phase, placebo participants gained weight linearly (M = 2.61 kg). exceeding both fluoxetine groups (30-mg group M = 1.33 kg, 60-mg group M = 1.25 kg). Weight suppression was initially greater for 60 mg than 30 mg, but both were followed by weight gain. Six months off drug produced greater dose-dependent weight rebound for 60 mg than 30 mg or placebo. Considering both on- and off-drug phases, weight gain for 60 mg of fluoxetine (M = 6.5 kg) was comparable with that for placebo (M = 4.7 kg) but greater than that for 30 mg (M = 3.6 kg). Fluoxetine appears to forestall postcessation weight gain, allowing time for the weight-conscious smoker to focus on quitting smoking rather than on preventing weight gain. To investigate whether the satiety-inducing agent sibutramine affected body weight and associated anthropometry in overweight and obese (body mass index (BMI) > 27) Type 2 diabetic patients on sulphonylurea therapy.
                A randomized, placebo-controlled trial was undertaken in 134 patients with stable metabolic control on chronic sulphonylurea therapy. Patients were placed on moderate caloric restriction and received treatment with either sibutramine (15 mg/day) or placebo for 6 months.
                Fifty-three of 69 sibutramine-treated and 57/65 placebo-treated patients completed the study. Both groups showed progressive weight loss. At the end of the trial weight loss was two times greater in the sibutramine group (mean +/- SEM; -4.5 +/- 0.5 kg) than placebo (-1.7 plus minus 0.5 kg, P < 0.001 vs. sibutramine). There was a trend for more patients to lose > 5% of initial body weight in the sibutramine group than placebo. BMI (P < 0.001) and waist circumference (P < 0.001) were also decreased to a greater extent by sibutramine. Mean reductions in HbA(1c) were commensurate with weight loss in both the sibutramine and placebo (- 0.78 +/- 0.17% and -0.73 +/- 0.23%; P = 0.84). Sibutramine was well tolerated with only two patients withdrawn due to potentially drug-related serious adverse events (palpitations).
                Sibutramine, in conjunction with moderate caloric restriction, enhances weight loss and reduces waist circumference in overweight and obese Type 2 diabetic patients receiving sulphonylurea therapy. This is associated with additional improvements in glycaemic control in a limited number of patients losing > or = 10% of their baseline body weight. We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment. In a six-week double-blind randomized trial, preceded by a one-week single-blind placebo treatment, the efficacy and the side-effects of fluoxetine (40-80 mg/d) (n = 30) and maprotiline (50-150 mg/d) (n = 35) were compared in hospitalized patients with DSM-III Major Depression without psychotic features. Efficacy was measured by means of the Hamilton Depression Rating Scale, the Raskin Depression Scale, the Covi Anxiety Scale, and a Clinical Global Impression. Side-effects were evaluated by an Adverse Events Scale. A statistically significant improvement was achieved in both treatment groups but success rates were modest. No differences in efficacy were found between the two groups. In addition, no statistically significant differences were found between the two groups either in frequency or in severity of adverse events. In fact, the only statistically significant difference found was in weight change: weight loss in the fluoxetine group and weight gain in the maprotiline group. 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. Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA) is a serotonin and norepinephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutraminetreated patients.
                Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function.
                A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean+/-Standard Deviation age was 54+/-9 years, and the mean duration of treatment was 229+/-117 days (approximately 7.6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 3/133, or 2.3%; placebo 2/77, or 2.6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension.
                The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7.6 months. Fluoxetine, an inhibitor of serotonin re-uptake, has been shown to cause weight loss in humans and animals. In order to determine the effects in diabetic subjects, 48 male and female, obese, type 2 non-insulin dependent diabetics being treated with insulin were randomized to receive fluoxetine 60 mg or placebo once daily in double blind fashion for 24 weeks. In all subjects, this treatment was preceded by four weeks and followed by six weeks of single blind placebo washout treatment. Subjects performed daily home glucose monitoring and were given instruction in a 1200 kcal American Diabetes Association diet. Fluoxetine treated subjects who completed the trial (n = 16) lost more weight than placebo treated subjects (n = 20) (9.3 +/- 2.4 vs. 1.9 +/- 2.9 kg +/- s.e.m, P less than 0.05). Subjects in the fluoxetine group also showed a greater percentage decrease in insulin dose than those in the placebo group (46.9 +/- 7.6% vs. 19.3 +/- 7.6%, P less than 0.01). During active treatment, the change in serum glucose levels did not differ between the two groups, while glycohemoglobin fell more in fluoxetine treated subjects than in placebo treated subjects at two of four follow-up visits. These results suggest that fluoxetine may be of benefit in the treatment of obese patients with type 2 non-insulin dependent diabetes mellitus. In a 12-month randomly allocated double-blind trial in 19 obese Type 2 diabetic patients, fluoxetine 60 mg daily compared to placebo produced a significant fall in median body weight after 3 months (3.8 kg), 6 months (6.5 kg), 9 months (7.1 kg) and at 1 year (5.8 kg). Median fasting blood glucose and HbA1c levels fell significantly after 3 months (1.9 mmol l-1) and 1.7%, respectively) and 6 months (1.8 mmol l-1 and 1.7%) but neither showed a significant difference to placebo after 9 or 12 months therapy with fluoxetine. There were no significant changes in serum cholesterol levels in the year but patients on fluoxetine showed a significant fall in serum triglyceride level (0.5 mmol l-1) after 3 months therapy but not thereafter. Compared to placebo there was a significant fall in median energy intake on fluoxetine after 3 months (257 kcal day-1) and 6 months (199 kcal day-1) but this difference was not significant at 9 or 12 months. There was also a significant fall in carbohydrate intake after 3 months (30 g day-1) and 6 months (23 g day-1) on fluoxetine as well as a significant fall in carbohydrate intake expressed as a percentage of the total daily energy intake; 5.9% at 3 months, 6.1% at 6 months, and 4.0% at 9 months. There were no significant effects on protein or fat intake except a significant increase in the intake of fat expressed as a percentage of daily energy intake, 5.9% after 6 months. Two of the nine patients on fluoxetine dropped out of the study due to gastrointestinal side-effects. Fluoxetine might prove to be a useful adjunct therapy in obese Type 2 diabetic patients where short-term weight loss and fall in carbohydrate intake and an improvement in glycaemia are indicated. Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.
                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.
                Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.
                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.
                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 randomized 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 rerandomized 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.
                Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.
                A total of 1187 subjects entered the protocol, and 892 were randomly 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.
                Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors. We evaluated the effects of 12-month treatment with sibutramine 15 mg daily compared with placebo on health-related quality of life (HRQL) in obese type II diabetes patients. We examined the associations between the changes in HRQL and in weight, glycaemic control, and haemodynamic variables. We also explored the predictive value of HRQL and its changes early during treatment.
                A randomised clinical trial. The subjects were enrolled in a 2-week single-blind run-in period with a modestly hypocaloric diet (700 kcal daily deficit) and then randomised to receive either sibutramine 15 mg (n=114, 60% female) or placebo (n=122, 58% female) once daily with the hypocaloric diet for 12 months.
                Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications.
                The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0).
                The mean weight loss was greater in the sibutramine group (-7.1 kg) than in the placebo group (-2.6 kg, P<0.001). The baseline HRQL was relatively high. There were no significant differences between the treatment groups in glycaemic control or in any of the RAND-36 scales during the study. The scores on physical functioning (PF) and health change (HC) since last year improved in both groups and this improvement was related to weight loss. When HRQL changes were examined in categories of weight loss, the scores on PF and HC increased with >/=5% weight loss, but the scores on vitality (V) and general health (GH) increased only after >/=15% weight loss. Decrease in HbA1c was associated with increases in the scores of PF, GH, V, mental health, and HC. In the sibutramine group, the increase in diastolic blood pressure was associated with the decrease in the scores of PF, physical role functioning, emotional role functioning (ERF), social functioning (SF), and bodily pain. High baseline scores on ERF and SF, and low scores on V predicted weight loss at 12 months. Also, increasing scores on PF and V during the first 3 months predicted weight loss at 12 months. The sum of four dichotomised HRQL variables (baseline ERF >/=75=1 and <75=0; baseline SF>/=80=1 and <80=0; 3-month change in PF>0=1 and </=0=0; 3-month change in V>0=1 and </=0=0) predicted weight loss: In the group with sum 0, the mean(s.d.) weight change at 12 months was 0.0(2.6)% and with sum 4 it was -9.0(8.1)% of baseline weight.
                Despite the superior weight loss, sibutramine 15 mg daily did not produce HRQL benefits over placebo when measured with the generic RAND-36 in obese type II diabetes patients. PF and HC since last year improved with >/=5% weight loss, but >/=15% weight loss was needed to achieve a cluster of HRQL improvements. The decrease in HbA1c was associated with many HRQL benefits. Poor baseline HRQL and the improvement observed in the first months of treatment may prove to be useful in predicting success in long-term weight loss. To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes.
                A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c), fasting glucose, and lipids.
                Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0 +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost > or = 10% weight showed significant decreases in both HbA(1c) (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of > or = 10% weight. Pulse rate increased significantly more with sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01).
                Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight. 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. 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. The prevalence of overweight and obesity in children and adolescents is increasing in both the United States and Mexico.
                The goal of this article was to assess the efficacy and safety of sibutramine in obese Mexican adolescents.
                This was a 6-month, randomized, double-blind, placebo-controlled, prospective clinical trial of sibutramine QD. Male and female patients aged 14 to 18 years with sex-specific body mass index (BMI) for age and sex >85th percentile were eligible. The primary end points for the trial were the baseline versus end point absolute values for body weight, BMI, and percentage of the initial BMI (%BMI); secondary end points were waist circumference and percentage of the initial waist circumference (%waist). These were measured at days -15, 0, 30, 60, 90, 120, 150, and 180 of the study. Quality of life was assessed at the study start and end using the 36-Item Short-Form Health Survey (SF-36) questionnaire. Blood pressure and heart rate were assessed, and adverse events (AEs) were recorded. Both groups received individually tailored diet and exercise programs.
                Forty-six patients (age range, 14-18 years) with a BMI >95th percentile for age were included (sibutramine group, n = 23 [14 females, 9 males]; placebo group, n = 23 [12 females, 11 males]). Twenty-one patients in the sibutramine group and 19 patients in the placebo group completed the 6-month trial. Using the intent-to-treat data, weight (mean [SD]) in the sibutramine group changed from 92.5 (14.6) kg to 85.7 (14.4) kg, for a net weight loss of 7.3 kg (95% CI 4.6-9.9), a waist circumference loss of 8.0 cm (95% CI, 4.7-11.3), and a % BMI loss of 9.2% (95% CI, 6.9-11.6). In the placebo group, weight changed from 98.9 (22.7) kg to 94.6 (22.5) kg, a weight loss of 4.3 kg (95% CI, 1.7-6.9), a waist circumference loss of 3.8 cm (95% CI, 0.7-7.0), and a %BMI loss of 5.2% (95% CI, 2.4-7.9) (P < 0.05 for all intragroup comparisons; P > 0.05 for the intergroup comparisons). Mean (SD) scores on the SF-36 scale in the sibutramine group changed from 78.0 (13.3) at baseline to 84.8 (7.4) at study end (P < 0.05); the respective values in the placebo group were 82.8 (10.3) and 87.3 (7.6) (P < 0.05). At base-line, systolic blood pressure (SBP) was 116.7 (5.9) mm Hg in the sibutramine group and 118.3 (7.6) mm Hg in the placebo group; at end point, the respective SBPs were 112.4 (9.6) mm Hg and 112.6 (6.5) mm Hg. At baseline, diastolic blood pressure (DBP) was 78.9 (4.5) mm Hg in the sibutramine group and 79.5 (5.2) mm Hg in the placebo group; at end point, the respective DBPs were 73.5 (6.3) mm Hg and 76.6 (6.2) mm Hg. At baseline, heart rate was 76.3 (6.4) beats/min in the sibutramine group and 81.1 (9.5) beats/min in the placebo group; at end point, the respective findings were 79.8 (8.8) beats/min and 77.6 (8.6) beats/min (P > 0.05 for all preceding intergroup comparisons). One patient in the sibutramine group had increased blood pressure (at month 3) and 3 had increased heart rate (at months 1, 2, and 4); 2 patients receiving placebo had increased blood pressure (month 3) and 2 had increased heart rate (at months 1 and 3). These changes disappeared in 1 week and did not require treatment or trial suspension. Additionally, in the sibutramine group, 3 patients experienced 4 mild AEs: headache, dry mouth, headache with nausea, and headache with weakness and paleness (P > 0.05). In the placebo group, 3 patients experienced 4 mild AEs: 2 cases of headache, as well as 1 case of headache with somnolence and 1 case of headache with dry mouth (P > 0.05).
                Sibutramine 10 mg QD in addition to diet and exercise was effective and generally well tolerated in this population of obese Mexican adolescents. To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat.
                Double-blind, parallel, randomized, placebo-controlled, multicentre study.
                Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline.
                After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low.
                Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile. Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained >/=3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n=31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD=19.1, last mean=83.5 kg, SD=19.8; placebo group: baseline mean=77.1 kg, SD=12.1, last mean=78.8 kg, SD=10.6; F=1.3; df=1, 18; p=0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade. Weight reduction on its own is observed to cause improvement in some of the abnormalities seen in patients with polycystic ovary syndrome (PCOS). With respect to this observation, we studied the possible effects of different serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels that might play a role in the obesity component seen in patients with PCOS. In a random design, sixteen patients were assigned to fluoxetine and sibutramine for a period of 10 days. In both treatment groups, no significant differences were observed between pre-treatment and post-treatment values in insulin levels (p > 0.05). There was no significant difference between pretreatment and post-treatment serum leptin levels in the fluoxetine treatment group (p > 0.05). However, a significant reduction was observed in the serum leptin levels at the end of treatment in the sibutramine group (p < 0.05). The observed difference in the serum leptin response to the treatment effect of sibutramine compared to fluoxetine seems to be due to a mechanism independent of serotonin reuptake inhibition, possibly to the thermogenic effect of the sibutramine itself. Further studies with larger groups are warranted, to examine the mechanism of the weight-reducing effect of sibutramine. Detailed analyses of basal metabolic activity and change in serum leptin levels should be carried out. To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months.
                The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo.
                The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3 +/- 7.3 to 82 +/- 7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105 +/- 29.3 versus 96.6 +/- 28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change.
                The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy. It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients.
                In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat.
                Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).
                Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction]. A large collaborative 8-week study has shown fluoxetine to be effective and safe in treating patients with bulimia nervosa. The present study evaluated fluoxetine over 16 weeks.
                Fifteen US out-patient psychiatry clinics conducted a double-blind parallel study in men and women with DSM-III-R bulimia nervosa (483 patients entered, 398 randomised [3:1 ratio, fluoxetine 60 mg/day or placebo], 225 completed). Outcome measures included change in vomiting and binge-eating episodes per week. Eating Disorder Inventory, Clinical Global Impressions and Patient's Global Impression.
                Compared with placebo, fluoxetine treatment resulted in significantly greater reductions in vomiting (F[1,360] = 14.73, P < 0.0001) and binge-eating (F[1,360] = 14.39, P = 0.0002) episodes per week at endpoint and improvement in other outcome measures. Adverse event, vital sign and laboratory analyses indicated that fluoxetine was safe.
                Fluoxetine appeared to be safe and effective in patients with bulimia nervosa for up to 16 weeks.
Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.