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1.
Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease.
Seimon, RV, Espinoza, D, Ivers, L, Gebski, V, Finer, N, Legler, UF, Sharma, AM, James, WP, Coutinho, W, Caterson, ID
International journal of obesity (2005). 2014;(9):1165-71
Abstract
BACKGROUND/OBJECTIVES 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 body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events. SUBJECTS/METHODS A total of 9804 male and female subjects, aged 55 years or older, 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 (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). 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 with factors for treatment, subgroups and interactions. RESULTS During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (-8.1±10.5 mm Hg with <5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs. CONCLUSION Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.
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2.
Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients.
Derosa, G, Maffioli, P, Salvadeo, SA, Ferrari, I, Gravina, A, Mereu, R, D'Angelo, A, Palumbo, I, Randazzo, S, Cicero, AF
Metabolism: clinical and experimental. 2011;(3):421-9
Abstract
The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight, glycemic control, insulin resistance, and inflammatory state in type 2 diabetes mellitus patients. Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >8.0%) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized 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, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, tumor necrosis factor-α, adiponectin, vaspin, and high-sensitivity C-reactive protein. Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose, postprandial plasma glucose, lipid profile, leptin, tumor necrosis factor-α, and high-sensitivity C-reactive protein compared with sibutramine alone. Furthermore, there was a better improvement of body weight, HbA(1c), fasting plasma insulin, homeostasis model assessment of insulin resistance index, vaspin, and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone. Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect.
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3.
Acute effect of weight loss on levels of total bilirubin in obese, cardiovascular high-risk patients: an analysis from the lead-in period of the Sibutramine Cardiovascular Outcome trial.
Andersson, C, Weeke, P, Fosbøl, EL, Brendorp, B, Køber, L, Coutinho, W, Sharma, AM, Van Gaal, L, Finer, N, James, WP, et al
Metabolism: clinical and experimental. 2009;(8):1109-15
Abstract
Low levels of bilirubin are associated with an increased risk of cardiovascular adverse events. Weight reduction is known to reduce several cardiovascular risk factors, but effects on bilirubin levels have not been reported. We studied the response of weight loss therapy with sibutramine and lifestyle change on levels of total bilirubin in an overweight or obese, cardiovascular high-risk population. Data from the first 4 weeks of the lead-in period of the Sibutramine Cardiovascular Outcome study were analyzed. A total of 10 198 patients provided body weight measurements before and after 4 weeks of sibutramine treatment (10 mg daily), of whom 1059 (10.4%) gained weight, 1467 (13.7%) lost greater than 0% to 1%, 2492 (23.2%) lost greater than 1% to 2%, 2280 (21.2%) lost greater than 2% to 3%, 1498 (13.9%) lost greater than 3% to 4%, and 1402 (13.1%) lost greater than 4% of their initial weight, respectively. At screening, bilirubin concentrations were similar between weight loss groups (around 11 micromol/L, P = .7) and increased linearly as a function of weight loss. The effect was significantly more pronounced in men compared with women (P for interaction = .003). Adjusted for multiple variables, each 1% increase in weight loss was associated with 0.21-micromol/L (+/- standard error 0.027) increase in men (P < .0001) and 0.11-micromol/L (+/-0.024) increase in women (P < .0001). Short-term weight loss during administration of sibutramine in combination with diet and exercise advice is effective in increasing bilirubin levels within the reference range, with bilirubin increasing as a linear function of weight change. The effect is greater in men than in women.
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4.
The cost-effectiveness of sibutramine in non-diabetic obese patients: evidence from four Western countries.
Ara, R, Brennan, A
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2007;(4):363-71
Abstract
This paper aims to assess the cost-effectiveness of sibutramine in treating obese patients in the Western countries. The model estimates the costs and quality of life benefits directly associated with weight losses combined with the costs and benefits associated with the reduced incidence of coronary heart disease (CHD) and diabetes. The pivotal effectiveness evidence is derived from a German multicentre, double-blind, randomized clinical trial on obese (body mass index ≥ 30 Euro kg m(-2)) patients. The incremental cost per quality-adjusted life year ranges from 10,734 Euro in Switzerland to 13,707 Euro in Germany. The total number of CHD events avoided ranges from 1.96 for the UK to 4.49 for Switzerland. The number of diabetes cases avoided is in the region of 3.0 (ranges from 2.58 for Germany to 3.28 for Switzerland). The majority of costs and benefits are accrued through sibutramine treatment and monitoring. Univariate sensitivity analyses show that results are sensitive to changes in the utility directly attributable to weight losses. The results demonstrate that the benefits associated with sibutramine-induced weight losses are obtained at a reasonable cost in each of the settings explored and suggest that sibutramine treatment could be considered as a viable option for pharmacotherapy treatment alongside diet and exercise.
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5.
Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study.
Scholze, J, Grimm, E, Herrmann, D, Unger, T, Kintscher, U
Circulation. 2007;(15):1991-8
Abstract
BACKGROUND Current guidelines for the treatment of hypertension do not provide specific recommendations for obese hypertensive patients. To identify an optimal treatment regimen for obese hypertensive patients, we studied the interactions between a drug-based weight loss approach by sibutramine and different antihypertensive drug regimens. METHODS AND RESULTS This was a prospective, 16-week double-blind placebo-controlled randomized multicenter study in 171 obese hypertensive patients. After a 2-week run-in period, patients receiving 1 of the 3 antihypertensive combination therapies (felodipine 5 mg/ramipril 5 mg [n=57], verapamil 180 mg/trandolapril 2 mg [n=55], or metoprolol succinate 95 mg/hydrochlorothiazide 12.5 mg [metoprolol/hydrochlorothiazide; n=59]) were assigned randomly to sibutramine (15 mg) or placebo. Sibutramine treatment resulted in a significantly greater decrease in body weight, body mass index, and waist circumference and a significant increase in diastolic blood pressure during 24-hour blood pressure monitoring compared with placebo treatment. Sibutramine-induced weight loss and reduction of visceral obesity were markedly attenuated in the metoprolol/hydrochlorothiazide group compared with the other groups. Consistently, improvement in glucose tolerance and hypertriglyceridemia by sibutramine was abrogated in the cohort treated with metoprolol/hydrochlorothiazide compared with the other groups. CONCLUSIONS The present study demonstrates for the first time that an antihypertensive combination therapy regimen with angiotensin-converting enzyme inhibitors and calcium channel blockers is more advantageous than a beta-blocker/diuretic-based regimen in supporting the weight-reducing actions and concomitant metabolic changes induced by sibutramine in obese hypertensive patients. These data may help to develop future comprehensive treatment strategies and guidelines for this high-risk patient population.
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6.
The effect of sibutramine on energy expenditure and body composition in obese adolescents.
Van Mil, EG, Westerterp, KR, Kester, AD, Delemarre-van de Waal, HA, Gerver, WJ, Saris, WH
The Journal of clinical endocrinology and metabolism. 2007;(4):1409-14
Abstract
CONTEXT Childhood obesity is now considered to be an epidemic. Drug therapy in this age group remains a topic of research. OBJECTIVE The objective of this study was to examine the effect of treatment with sibutramine (10 mg) on body composition and energy expenditure in obese adolescents. DESIGN The study was conducted as a randomized, double-blind, placebo-controlled trial. SETTING The study was set in an obesity research center. PATIENTS The patients were 24 obese adolescents (age 12-17 yr, 11 boys); four patients withdrew. INTERVENTION Intervention was sibutramine (Meridia) or placebo in combination with an energy-restricted diet and exercise plan for 12 wk, followed by an identical, but medication-free, treatment period (follow-up). MAIN OUTCOME MEASURE Change in body mass index (BMI) sd score (BMI-SDS) was the principal measure of efficacy. Body composition and total energy expenditure were measured by stable isotopes and further calculated according to the four-component model, using underwater weighing and dual x-ray absorptiometry. Basal metabolic rate (BMR) was measured by ventilated hood and adjusted for sex and body composition (BMRadj). RESULTS After intervention, the decrease in BMI-SDS was comparable in both groups. During follow-up, BMI further decreased in the placebo group but stabilized in the sibutramine group. Changes in the percentage of fat mass were not different between both groups. BMRadj decreased in the placebo group and remained constant in the sibutramine group. During follow-up, BMRadj decreased in the sibutramine group and increased in the placebo group. Changes in total energy expenditure were not significantly different. CONCLUSION The effect of sibutramine on BMI-SDS was not significant. Sibutramine may diminish the decrease in BMRadj associated with energy restriction in obese adolescents.
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7.
Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes.
Kaukua, JK, Pekkarinen, TA, Rissanen, AM
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2004;(4):600-5
Abstract
OBJECTIVE 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. DESIGN 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. SUBJECTS Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications. MEASUREMENTS The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0). RESULTS 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. CONCLUSION 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.
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8.
Croatian experience with sibutramine in the treatment of obesity--multicenter prospective study.
Stimac, D, Ruzić, A, Majanović, SK
Collegium antropologicum. 2004;(1):215-21
Abstract
Obesity is a chronic disease with a marked impact on health and the prevalence of obesity in Croatia is rapidly rising. Since obesity plays a significant role in the etiology of cardiovascular diseases, diabetes mellitus type 2 and of some cancers, it is an obvious target of public health activities. Weight-reducing drugs, like sibutramine, in combination with diet, exercise and behavioral changes have a role in the management of obesity. Sibutramine acts centrally as a serotonergic and noradrenergic reuptake inhibitor. It reduces body weight by enhancing satiety and stimulating thermogenesis. The aim of this multicenter prospective study was to evaluate the efficacy, tolerability and safety profile of sibutramine in the treatment of overweight patients in Croatia. Patients received 10 mg of sibutramine daily for 12 weeks. The main outcome measures were changes in body weight, BMI, waist and hip circumferences, laboratory assessments (serum triglicerida, cholesterol, glucose, HbA1c), blood pressure and heart rate profile. Of 461 patients included (mean BMI = 35.81+/-6.48 kg/m2, mean age = 43.65+/-10.90 years), 392 completed the study. Three months of sibutramine treatment lead to a significant reduction in body weight, BMI, waist and hip circumferences and improvement in metabolic parameters. Loss of over 5% of their initial body weight was found in 359 patients (91.58%), while 179 patients (45.66%) achieved weight loss over 10%. A decrease of both systolic (-3.39%) and diastolic (-3.75%) blood pressure was noted, while the pulse rate rose slightly (+0.13%). Adverse events were reported by 124 (26.90%) patients, but they precipitated only 17 (3.69%) withdrawals. Results of our study confirmed that sibutramine is an effective and safe weight-reducing drug.
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9.
A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin.
McNulty, SJ, Ur, E, Williams, G, ,
Diabetes care. 2003;(1):125-31
Abstract
OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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). CONCLUSIONS 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.
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10.
Effects of sibutramine on body weight and serum lipids: a double-blind, randomized, placebo-controlled study in 322 overweight and obese patients with dyslipidemia.
Dujovne, CA, Zavoral, JH, Rowe, E, Mendel, CM, ,
American heart journal. 2001;(3):489-97
Abstract
BACKGROUND Cardiovascular risk factors associated with obesity, including dyslipidemia, can be improved by weight loss. The main dyslipidemia associated with obesity is elevated serum triglyceride and decreased serum high-density lipoprotein cholesterol (HDL-C) levels. METHODS A total of 322 obese patients (body mass index > or = 27) with serum triglyceride levels > or = 250 mg/dL and < or = 1000 mg/dL and serum HDL-C levels < or = 45 mg/dL (women) and < or = 40 mg/dL (men) were placed on a step I American Heart Association diet and subsequently randomized to sibutramine 20 mg (n = 162) or placebo (n = 160) once daily for 24 weeks. RESULTS Patients taking sibutramine had significantly greater mean weight loss than those receiving placebo (-4.9 kg vs -0.6 kg, P < or = .05). Forty-two percent of the sibutramine group lost > or = 5% of baseline weight and 12% lost > or = 10% compared with 8% and 3%, respectively, of the placebo group (P < or = .05). Mean decreases in serum triglyceride levels among 5% and 10% weight-loss responders in the sibutramine group were 33.4 mg/dL and 72.3 mg/dL, respectively, compared with an increase of 31.7 mg/dL among all patients receiving placebo (P < or = .05). Mean increases in serum HDL-C levels for 5% and 10% weight-loss responders in the sibutramine group were 4.9 mg/dL and 6.7 mg/dL, respectively, compared with an increase of 1.7 mg/dL among all patients in the placebo group (P < or = .05). Adverse events and discontinuation rates were similar in the sibutramine and placebo groups, although sibutramine-treated patients had mean increases in systolic and diastolic blood pressure of 2 to 3 mm Hg relative to placebo. CONCLUSIONS In overweight and obese patients with high serum triglyceride levels and low serum HDL-C levels, treatment with sibutramine was associated with significant improvements in body weight and in serum triglyceride and HDL-C levels.