Long-Term Weight Loss With Sibutramine. A Randomized Controlled Trial - Long-Term Weight Loss With Sibutramine. A Randomized Controlled Trial

Description:

Long-Term Weight Loss With Sibutramine. A Randomized Controlled Trial.

Hypothesis:

Sibutramine enhances satiety by blocking the re-uptake of the neurotransmitters noradrenaline and seratonin, and may increase metabolic rate and energy expenditure for a given activity. This study was designed to determine the efficacy of continuous and intermittent sibutramine in moderately obese persons.

Study Design

Study Design:

Mean Patient Age: 18-65
Female: 75

Drug/Procedures Used:

A randomized double-blind parallel-group placebo-controlled trial comparing 15 mg/day of sibutramine for 48 weeks (n=405), 15 mg/day of sibutramine for 12-week blocks, which were interrupted twice by 7 weeks of placebo in 48 weeks (395), or 4 weeks of sibutramine followed by 44 weeks of placebo (n=201). The study was conducted in 18-65-year-old German patients who had failed at least one dietary weight loss effort. Entry criteria required a body mass index (BMI) of 30-40kg/m2.

Principal Findings:

About 75% were female, mean age was 43 years, BMI 34.8kg/m2 and a family history of obesity was present in 73%. Overall weight loss during the 48-week period was 7.9kg and 7.8kg in the continuous and intermittent sibutramine groups and 3.8kg in the sibutramine 4-week run in placebo group. Mean weight loss during the 44-week comparative period was 3.8kg (4%) on continuous sibutramine, 3.3kg (3.5%) on intermittent therapy, which were equivalent and each significantly greater than placebo that had a weight gain of 0.2kg (0.2%). 60% of patients on active treatment lost at least 5% of their weight compared to 35% of those on placebo. Waist circumference, triglycerides and HDL-C improved on sibutramine, but there was no change in blood pressure in any group. Approximately 20% withdrew from the study with the highest number on placebo. Typical side effects of sibutramine included dry mouth, constipation and sweating, which decreased with prolonged exposure.

Sibutramine, administered for 48 weeks to a typically obese population, results in clinically relevant weight loss compared to placebo. Continuous and intermittent therapies are equivalent.

Interpretation:

Sibutramine appears to be a safe and relatively effective drug therapy for weight loss and reducing cardiovascular risk factors in obesity. The failure to lower the blood pressure likely reflects the sympathomimetic effect of sibutramine, which may be associated with an increase in blood pressure. Unfortunately, the weight, blood pressure and impact on other risk factors 2-12 weeks after withdrawl of sibutramine were not part of this report and are essential in the assessment of this strategy for obesity. There are no reports of sibutramine-induced pulmonary hypertension.

References:

1. Wirth A, Krause J. JAMA 2001;286:1331-9.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, Hypertriglyceridemia, Lipid Metabolism, Pulmonary Hypertension

Keywords: Sweating, Weight Loss, Risk Factors, Norepinephrine, Weight Gain, Cyclobutanes, Neurotransmitter Agents, Sympathomimetics, Waist Circumference, Body Mass Index, Constipation, Hypertension, Pulmonary, Obesity, Energy Metabolism, Triglycerides


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