Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory to dietary management. Weight reduction by sibutramine in obese subjects in primary care medicine: the SAT Study. Treatment of obese adolescents with sibutramine: a randomized, double-blind, controlled study. Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study. Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial.
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. 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. 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. 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. 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 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 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. 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. 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.
Orlistat, sibutramine and rimonabant have been studied in trials of one year or longer. Internal validity of studies was limited by high attrition rates. All three antiobesity agents are modestly effective in reducing weight and have differing effects on cardiovascular risk and adverse effects profiles. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required.