Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.

London School of Hygiene and Tropical Medicine, London, England.
New England Journal of Medicine (Impact Factor: 55.87). 09/2010; 363(10):905-17. DOI: 10.1056/NEJMoa1003114
Source: PubMed


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.)

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    • "Based on emerging concerns and findings from the SCOUT study (James et al., 2010), the manufacturer withdrew sibutramine from the market in 2010 (Reas & Grilo, 2014), at which time enrollment in this RCT was stopped. However, the present study nonetheless provides important information about the effectiveness of sibutramine and the potential benefits of combining an anti-obesity agent with shCBT. "
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    ABSTRACT: Objective 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. Method 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). Results 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. Discussion 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.
    Behaviour Research and Therapy 07/2014; 58. DOI:10.1016/j.brat.2014.04.002 · 3.85 Impact Factor
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    • "Given the high international prevalence of obesity and the substantive costs of management of the associated co-morbidities, the need to develop pharmacological strategies to reduce appetite and support weight-control regimes has never been greater. As of 2013, there are no centrally-acting drugs that can be prescribed in the USA or Western Europe for this purpose, the most recently available compounds sibutramine (a monoamine reuptake inhibitor) and rimonabant (an endocannabinoid receptor antagonist) having been withdrawn because of adverse side effects (James et al., 2010; Rothman and Baumann, 2009). Clearly there is a huge need to understand better the complex behavioral mechanisms that underlie our motivation to eat in order to identify feasible drug targets, but our use of animals to achieve this is hugely skewed toward a few 'model' species. "
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    • "document_librar y/Press_release/2010/01/ WC500069995.pdf accessed 21 August 2013) and the USA as a fallout from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial [James et al. 2010] that showed a higher frequency of nonfatal myocardial infarction and stroke in subjects on sibutramine treatment compared with placebo. Rimonabant and sibutramine were the latest in a long line of centrally acting antiobesity drugs (Table 1) that have been linked with major safety concerns [Rodgers et al. 2012]. "
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