The effect of sibutramine on adolescent cardiovascular health was a matter of concern when the first pediatric data became available.85 Greater reductions in cardiovascular variables, including change in systolic and diastolic blood pressure, and pulse rate were generally seen in placebo treated adolescents despite the greater weight loss in the sibutramine treated groups. Statistically significant differences favoring placebo were found for systolic blood pressure,37 diastolic blood pressure78, 84 and heart rate.37, 78 Adult studies confirmed sibutramine increases blood pressure and heart rate.86, 87 In September 2010, SCOUT (Sibutramine Cardiovascular Outcomes Trial), a multinational, randomized, placebo controlled trial conducted in 16 countries, with a mean of 3.4 years of duration designed to assess clinical outcome in subjects with high risk of cardiovascular events,88 found that 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. The risk of a primary outcome event was 11.4 in the sibutramine group as compared with 10.0 in the placebo group.88 These findings resulted in an FDA request to withdraw sibutramine from the US market.89 Apart from cardiovascular outcomes, other adverse effects included dry mouth, insomnia, constipation, headache and cholelithiasis. # what is meizitang botanical slimming soft gels (e) Cannabinoid (CB) receptor inhibitors: Stimulation of central CB1 receptors increases appetite and fat deposition. Clinical trials of rimonabant, a selective endocannabinoid (CB1 receptor) antagonist, indicated beneficial effects on weight, waist circumference, serum lipids, C reactive protein and glycemic control in adult patients with type 2 diabetes.128, 129 The major adverse effects of rimonabant included nausea, anxiety and depression.130 The FDA did not approve rimonabant in 2007 because of concerns about neuropsychiatric adverse effects, particularly an increase in suicidality. Approved as a weight loss medication in Europe in 2006, rimonabant was withdrawn by the European Medicines Agency in 2009 because of an increase in psychiatric adverse effects.131 Clinical development of rimonabant as well as other centrally acting CB1 inhibitors such as taranabant and otenabant was suspended as a result of this adverse event profile.73, 132, 133 More recent findings on CB1 receptor antagonism in the liver, adipocytes, muscle and pancreas have raised hopes for potentially new generation of peripherally acting CB1 receptor inhibitors for treatment of obesity and its comorbid conditions such as fatty liver, insulin resistance and dyslipidemia.134, 135, 136, 137.
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