Sibutramine Group Research Articles

Comparison of the effects of liraglutide and sibutramine in obese patients

Background: Obesity is a global noncommunicable pandemic. The low effectiveness of treating obesity is associated with the difficulty of maintaining weight loss due to the reaction of the appetite regulation system. Drugs with central mechanisms of action can help overcome this problem.Aim: The aim of our study was to compare the effects of liraglutide and sibutramine (Reduxin) on the dynamics of weight and cardiometabolic parameters in obese patients without cardiovascular diseases.Materials and methods: We estimated the dynamics of the main metabolic parameters (BMI, glucose, lipid metabolism, blood pressure), the level of hormones involved in the regulation of fat metabolism (leptin, adiponectin, insulin), the ­HOMA-IR index, markers of oxidative stress and inflammation during therapy with liraglutide in comparison with reduxin for 6 months in obese patients.Results: 64 obese patients were included in the study: 25 patients — in the “Liraglutide” group, 39 patients — in the “Sibutramine” group in accordance with the declared inclusion / exclusion criteria. The included patients were young, average body mass index (BMI) (37.92 ± 5.45 kg / m2), average glycemic level was 5.47 ± 0.81 mmol /l, HOMA-IR was 6.01 ± 4.25, blood pressure was at inclusion was within the normal range, but 21.8% of patients received antihypertensive therapy.Both treatment options provided a comparable decrease in body weight (-10.28% vs -9.47%, p = 0.13)., Leptin level (-32.12% vs -41.77%, p = 0.77) and myeloperoxidase (-33.33% vs -19.91%, p = 0.2). The blood pressure level did not change significantly on liraglutide, while on reduxin the level of diastolic blood pressure (dBP) increased significantly (6.87%, p = 0.006). There was a more pronounced decrease in insulin levels compared to the baseline level (-46%, p = 0.005), as well as a decrease in the HOMA-IR index (-50.08, p = 0.005) on liraglutide therapy.An increase in adiponectin levels (+ 45.36% vs 14.01%, p = 0.0045) and a decrease in low density lipoprotein(LDL) cholesterol were significantly more pronounced on reduxin therapy (-15.03% vs -9.4%, p = 0.006).36% of the participants completed their participation in the study ahead of schedule due to the lack of effect in the form of weight loss in the «Liraglutide» group. Side effects in the “Liraglutide” group were observed in 16% of patients. 48% of patients took part in the study within 6 months. In the «Sibutramine» group 33.4% of patients completed the study ahead of schedule for reasons unrelated to the drug intake, the side effects were observed in 20.5% of patients. 46.1% of participants in the «Sibutramine» group received therapy for 6 months.Conclusions: This study confirms the previous findings that both liraglutide and reduxin therapy provide effective weight loss. We found a positive trend in markers of inflammation, atherogenesis and oxidative stress, and leptin levels. Liraglutide therapy was accompanied by a more pronounced effect on the state of carbohydrate metabolism, and reduxin therapy provided a more pronounced dynamics of lipid disorders and adiponexin. Both groups were characterized by a rather low adherence to therapy, but the incidence of side effects requiring stopping therapy was higher in the Sibutramine group.

Outcomes with Intra-gastric Balloon Therapy in BMI < 35 Non-morbid Obesity: 10-Year Follow-Up Study of an RCT.

Intra-gastric balloon (IGB) therapy is the most established endoscopic treatment of obesity, but there is a paucity of literature on long-term efficacy. This study aims to evaluate the short- and long-term weight loss efficacy of IGB. Double-blinded RCT with 6-month IGB vs with sham endoscopy, in body mass index (BMI) 27-35 patients. Anthropometric, fasting glucose, and lipid profile measurement as early outcomes (up to 2years) and 10-year follow-up. Primary outcomes were total body weight loss (kg) and BMI. Secondary outcomes were new-onset diabetes mellitus, other new comorbidities, and willingness for further intervention. Initial RCT recruited 99 patients (50 IGB vs 49 sibutramine group). Forty-nine patients (26 IGB vs 23 control group) participated in a 10-year review (follow-up rate of 51.6%). Total body weight loss at 6 (9.75 vs 7.48kg, p = 0.03), 12 (6.52 vs 4.42kg, p = 0.05), 18 (5.42 vs 3.57, p = 0.32), and 24months (4.07 vs 2.93kg, p = 0.56) favored the IGB group. Total weight loss (TWL) at 10years (0.03 vs - 2.32kg, p = 0.05) and %TWL (- 0.16 ± 12.8% vs - 2.84 ± 5.6%, p = 0.39) were not significantly different between groups. Follow-up BMI (30.97 ± 1.6 vs 30.38 ± 1.8kg/m2, p = 1.00) was similar. At 10years, new-onset diabetes mellitus, sleep apnoea, metabolic syndrome, and arthralgia were not significant (p > 0.05). Twenty-three (81%) IGB group vs 13 (56%) control expressed a willingness for further intervention (p < 0.01). IGB delivers weight loss to 2years and is superior to control. However, new comorbidity development is not significantly different at 10years. Patient that received IGB therapy were subsequently more willing for further bariatric metabolic intervention.

Metabolic and Inflammatory Changes with Orlistat and Sibutramine Treatment in Obese Malaysian Subjects

Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Influence of sibutramine in addition to diet and exercise on the relationship between weight loss and blood glucose changes.

Weight loss is expected to improve glycaemic control in patients with diabetes or at high risk hereof. Sibutramine causes weight loss and is associated with an increased risk of myocardial infarction and stroke in high-risk patients. We examined the impact of sibutramine-induced weight loss on glycaemic control. In total, 8192 obese patients with diabetes were randomized to sibutramine or placebo plus diet and exercise after a preliminary 6 weeks in which all patients received sibutramine. Patients were classified into four groups of weight change. A total of 1582 patients had a weight loss >5.7 kg; 2047 patients lost 3.7-5.7 kg; 2432 patients lost <3.7 kg, and 1875 patients gained weight. Patients on sibutramine lost slightly more weight than those on placebo (-0.2 kg on average, P < 0.0001). Mean blood glucose changes in the placebo group were -0.6 mmol/L (±3.1, P = 0.0002), -0.2 mmol/L (±2.7, P = 0.04), and -0.1 mmol/L (±3.0, P = 0.01) in the moderate, modest, and mild weight loss groups, respectively; in the weight gain group blood glucose levels increased by +0.2 mmol/L (±3.1, P = 0.003). Corresponding mean blood glucose changes in the sibutramine-treated patients were -0.4 mmol/L (±3.2, P = 0.0002), +0.1 mmol/L (±3.0, P = 0.04), +0.4 mmol/L (±2.8, P = 0.01), and +0.2 mmol/L (±3.4, P = 0.003). Mean values of HbA1c followed the same pattern though the HbA1c changes were smaller with weight loss and greater with weight gain in the sibutramine group. All results were statistically significant (P < 0.0001). Weight loss induced by sibutramine, diet, and exercise attenuates falls in blood glucose levels and HbA1c compared with similar weight loss with placebo, diet, and exercise.

Changes in body weight and pulse: outcome events in overweight and obese subjects with cardiovascular disease in the SCOUT trial.

The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in pulse rate, and the impact of these changes on subsequent cardiovascular outcome events in both the placebo and sibutramine groups. 9804 males and females, aged ⩾55 years, with a body mass index of 27-45 kg m(-)(2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor, to assess cardiovascular outcomes. The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models. During the initial 6-week sibutramine treatment period, the induced pulse rate increase was related to weight change (1.9±7.7 beats per minute (bpm) with weight increase; 1.4±7.3 bpm, 0-5 kg weight loss; 0.6±7.4 bpm, ⩾5 kg weight loss). Throughout the subsequent treatment period, those continuing on sibutramine showed a consistently higher mean pulse rate than the placebo group. There was no difference in POE rates with either an increase or decrease in pulse rate over the lead-in period, or during lead-in baseline to 12 months post randomization. There was also no relationship between pulse rate at lead-in baseline and subsequent cardiovascular events in subjects with or without a cardiac arrhythmia. Baseline pulse rate and changes in pulse rate may not be an important modifier nor a clinically useful predictor of outcome in an individual elderly cardiovascular obese subject exposed to weight management.

Treatment of binge eating disorder in racially and ethnically diverse obese patients in primary care: Randomized placebo-controlled clinical trial of self-help and medication

The objective was to determine whether treatments with demonstrated efficacy for binge eating disorder (BED) in specialist treatment centers can be delivered effectively in primary care settings to racially/ethnically diverse obese patients with BED. This study compared the effectiveness of self-help cognitive-behavioral therapy (shCBT) and an anti-obesity medication (sibutramine), alone and in combination, and it is only the second placebo-controlled trial of any medication for BED to evaluate longer-term effects after treatment discontinuation. 104 obese patients with BED (73% female, 55% non-white) were randomly assigned to one of four 16-week treatments (balanced 2-by-2 factorial design): sibutramine (N = 26), placebo (N = 27), shCBT + sibutramine (N = 26), or shCBT + placebo (N = 25). Medications were administered in double-blind fashion. Independent assessments were performed monthly throughout treatment, post-treatment, and at 6- and 12-month follow-ups (16 months after randomization). Mixed-models analyses revealed significant time and medication-by-time interaction effects for percent weight loss, with sibutramine but not placebo associated with significant change over time. Percent weight loss differed significantly between sibutramine and placebo by the third month of treatment and at post-treatment. After the medication was discontinued at post-treatment, weight re-gain occurred in sibutramine groups and percent weight loss no longer differed among the four treatments at 6- and 12-month follow-ups. For binge-eating, mixed-models revealed significant time and shCBT-by-time interaction effects: shCBT had significantly lower binge-eating frequency at 6-month follow-up but the treatments did not differ significantly at any other time point. Demographic factors did not significantly predict or moderate clinical outcomes. Our findings suggest that pure self-help CBT and sibutramine did not show long-term effectiveness relative to placebo for treating BED in racially/ethnically diverse obese patients in primary care. Overall, the treatments differed little with respect to binge-eating and associated outcomes. Sibutramine was associated with significantly greater acute weight loss than placebo and the observed weight-regain following discontinuation of medication suggests that anti-obesity medications need to be continued for weight loss maintenance. Demographic factors did not predict/moderate clinical outcomes in this diverse patient group.

Sibutramine in the treatment of antipsychotic-induced weight gain

Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

MRI allows for longitudinal quantitative analysis of body fat composition in rats: An analysis of sibutramine-associated changes at the group level

PurposeBody fat distribution changes are associated with multiple alterations in metabolism. Therefore, the assessment of body fat compartments by MRI in animal models is a promising approach to obesity research. Standard T1-weighted (T1w) whole body MRI was used here to quantify different effects in the subcutaneous and visceral fat compartments in rats under treatment with an anorexiant. Materials and methodsTwenty rats on a high caloric diet were investigated by the identical MRI protocol at baseline and after seven weeks. Ten rats received a treatment with sibutramine, 10 rats served as vehicle control group. To longitudinally assess body fat components, MRI analysis was used with two approaches: 2D slicewise graphic analysis (SGA) was compared with an automated 3D analysis algorithm (3DA). ResultsAt the group level, fat volume differences showed a longitudinal increase of subcutaneous and visceral fat volumes for the control group, whereas the sibutramine group showed stable subcutaneous fat volumes and decrease in visceral fat volumes. SGA and 3DA volume determination showed significant correlations for subcutaneous fat volume (C=0.85, p<0.001), visceral fat volume (C=0.87, p<0.001), and total fat volume (C=0.90, p<0.001). ConclusionIt could be demonstrated that computer-based analysis of T1w MRI could be used to longitudinally assess changes in body fat compartments in rats at the group level. In detail, it was possible to investigate the effect of sibutramine separate on the fat compartments in rats.

The effect of sibutramine on weight loss in obese adolescents

To evaluate the effect of sibutramine on weight loss in obese adolescents. A double-blind controlled study lasting 13 months. The study included 73 obese adolescents of both sexes aged between 10 and 18 years. Laboratory tests and imaging studies were performed before, during wash-out, and at the end of 13 months. The percentage of patients who lost 10% of their initial weight in the placebo group was 46%, and in the sibutramine group was 75%. When placebo was used, average weight rose by 1.61 kg, and BMI decreased by 0.24 kg/m(2) whereas with the use of sibutramine, weight decreased by 4.47 kg, and average BMI decreased, 2.38 kg/m(2), with p < 0.001. Sibutramine induced significantly more weight loss in obese adolescents compared with placebo, without significant side effects. The weight loss curve was different depending on the moment sibutramine was introduced. This finding indicates that the best time to start sibutramine is when adhesion begins to fail.

Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome

To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment. Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment. A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH.

Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial

The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups.

Effect of Sibutramine on 5‐Hydroxyindole Acetic Acid Levels and Selected Oxidative Biomarkers on Brain Regions of Female Rats in the Presence of Zinc

A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 μg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects.

Hepatic PTP1B Expression Involvement in the Effects of Chinese Medicine Formula Xiao-Gao-Jiang-Zhuo Using an Obese Rat Model

In this study, we investigated the effects of a Chinese herbal medicine formula xiao-gao-jiang-zhuo (XGJZ) in obese rats induced by a high-fat diet. Ten male rats in the normal group were fed with a standard diet. Another 50 male obese rats were induced by a 12-week high-fat diet feeding, and were randomly divided into five groups (n = 10 per group): the model group, the high-dose XGJZ group, the middle-dose XGJZ group, the low-dose XGJZ group, and the sibutramine group. After 14 weeks of treatment, body weight, abdominal fat, blood lipid and serum insulin level were measured, and the protein and gene expression of PTP1B in liver tissue was tested. Our data showed that the body weight of the high-dose and middle-dose groups and the sibutramine group had significant differences in comparison with the model group (p < 0.05), and all three dose groups had significantly reduced abdominal fat (p < 0.05). The triglyceride level of the three dose groups and the sibutramine group, and the total cholesterol level of the middle-dose group were all significantly reduced (p < 0.05). The serum insulin of the high-dose and middle-dose groups also decreased significantly (p < 0.05). The expression of hepatic PTP1B mRNA of the three dose groups decreased significantly in comparison with the model group (p < 0.05 or 0.01). The expression of hepatic PTP1B protein of the high-dose and middle-dose groups decreased significantly (p < 0.05). Our data suggested that XGJZ can modulate the body weight, abdominal fat and blood lipid in the obese rats, and this modulation might improve insulin resistance by inhibiting the PTP1B signal pathway.

Effects of One Year Treatment of Sibutramine on Insulin Resistance Parameters in Type 2 Diabetic Patients

Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: homeostasis model assessment insulin resistance index (HOMA-IR), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP), body weight, body mass index (BMI), glycated hemoglobin (HbA(₁c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglycerides (T(g)). A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups, and a faster improvement of HbA(₁c), FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. Sibutramine gave a faster improvement of insulin resistance parameters and glycemic control compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight.

Effect of Sibutramine on Cardiovascular Outcomes in Overweight and Obese Subjects

The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

A common variant in the adiponectin gene on weight loss and body composition under sibutramine therapy in obesity

In this study, we aimed to explore whether a common single nucleotide polymorphism (SNP), rs266729 (-11,377C > G), in the adiponectin C1Q and collagen domain containing (ADIPOQ) gene could influence weight reduction and fat change under sibutramine therapy in an obese population. There were 131 obese Taiwanese patients, including 44 in the placebo group and 87 in the sibutramine (10 mg daily) group. We assessed the measures of weight loss and body fat reduction at the end of the 12-week treatment period by analysis of covariance (ANCOVA) models using gender, baseline weight, and baseline percent body fat as covariates. By comparing the placebo and sibutramine groups with ANCOVA, our data revealed a strong effect of sibutramine on percent body fat loss (1.9 ± 0.3 vs 4.6 ± 0.5%; P < 0.001) and on weight reduction (2.8 ± 2.0 vs 7.9 ± 1.6 kg; P < 0.001) for subjects with the CC genotype. On the contrary, sibutramine had no significant effect on percent body fat loss or on weight loss in the GG and GC individuals. The results suggest that the SNP rs266729 of the ADIPOQ gene may contribute to weight reduction and fat loss in response to sibutramine therapy in Taiwanese obese patients.

Sibutramine Effects on the Reproductive Performance of Pregnant Overweight and Non-Overweight rats

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. On d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

Effect of the Common -866G/A Polymorphism of the Uncoupling Protein 2 Gene on Weight Loss and Body Composition under Sibutramine Therapy in an Obese Taiwanese Population

Sibutramine, a serotonin and norepinephrine reuptake inhibitor, is used as an anti-obesity drug. Several pharmacogenetic studies have shown correlations between sibutramine effects and genetic variants, such as the 825C/T (rs5443) single nucleotide polymorphism (SNP) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene. In this study, our goal was to investigate whether a common SNP, -866G/A (rs659366), in the uncoupling protein 2 (UCP2) gene could influence weight reduction and body composition under sibutramine therapy in an obese Taiwanese population. The study included 131 obese patients, 44 in the placebo group and 87 in the sibutramine group. We assessed the measures of weight loss and body fat reduction at the end of a 12-week treatment period by analysis of covariance (ANCOVA) models using gender, baseline weight, and body fat percentage at baseline as covariates. By comparing the placebo and sibutramine groups with ANCOVA, our data showed a strong effect of sibutramine on weight loss in the combined UCP2 -866 AA + GA genotype groups (p < 0.001). Similarly, a strong effect of sibutramine on body fat percentage loss was found for individuals with the AA or GA genotypes (p < 0.001). In contrast, sibutramine had no significant effect on weight loss (p = 0.063) or body fat percentage loss (p = 0.194) for individuals with the wild-type GG genotype, compared with the placebo group of the same genotype. Moreover, a potential gene-gene interaction between UCP2 and GNB3 was identified by multiple linear regression models for the weight loss (p < 0.001) and for the percent fat loss (p = 0.031) in response to sibutramine. The results suggest that the UCP2 gene may contribute to weight loss and fat change in response to sibutramine therapy in obese Taiwanese patients.

Sibutramine and L-Carnitine Compared to Sibutramine Alone on Insulin Resistance in Diabetic Patients

To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight, glycemic control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) >8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). There was a decrease in body weight, BMI, HbA(1c), FPI, HOMA-IR, and RBP-4 in both groups, even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group. There was a faster decrease of FPG, PPG, TC, LDL-C, resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained. Furthermore, only sibutramine plus L-carnitine improved Tg, and visfatin. Sibutramine plus L-carnitine gave a faster improvement of lipid profile, insulin resistance parameters, glycemic control, and body weight compared to sibutramine.

Comparison of rimonabant and sibutramine treatment effects on food compulsion in rats

To compare the therapeutic effect of rimonabant, a new drug which is a selective antagonist of CB1 receptors, with the sibutramine. It is an experimental clinical trial, prospective, placebo controlled. Our test was performed in 38 rats, adults females with a hyper caloric diet. We collected their blood 3 times and weighted them once a week. We divided the rats in 3 groups: Rimonabant, Sibutramine and Control. Statistic analysis has been made through ANOVA test, Tukey test and t Student test. The Rimonabant group demonstrated a significant reduction of the weight increase in rats. The Sibutramine group showed a significant reduction on blood glycemia compared to Rimonabant group and Control group. Rimonabant showed to be more effective than Sibutramine by decreasing weight gain. Sibutramine has been more effective than Rimonabant and Control groups by decreasing the blood glycemia.