Six-Month Trial Of Sibutramine For Obesity Treatment - Brief Article - Statistical Data Included

Nutrition Research Newsletter, May, 2000

Sibutramine (Meridia), a new drug approved for the long-term treatment of obesity, is a serotonin and noradrenaline reuptake inhibitor, which produces weight loss by enhancing satiety and increasing the metabolic rate in rodent systems. The dual mechanism of action depends on the balanced inhibition of the serotonin and noradrenaline reuptake. Sibutramine does not release monoamines and has no affinity for their receptors. The effects of sibutramine are mediated by two active demethylated metabolites. The hypophagic effect of sibutramine has been demonstrated in humans. The thermogenic effect in humans remains unclear, as previous studies have conflicting results regarding change in resting metabolic rate and energy expenditure. A double-blind, placebo-controlled, parallel, prospective clinical trial was recently conducted to evaluate the safety and efficacy of sibutramine in obese Hispanic patients undergoing a program that included dietary advice over a period of six months.

Black and Hispanic populations have a higher prevalence of overweight and obesity than the non-Hispanic white group. For this reason, male and female Hispanic patients aged 16 to 65 years with a body mass index (BMI) [is greater than] 30 were included in the study. Patients were randomized to either the group taking sibutramine 15 mg orally once per day or the group taking the placebo. The study was conducted between January 1997 and June 1998. Patients were recommended to consume a diet of 30 kcal/kg of ideal body weight, according to weight charts for Mexican adults. The suggested diet had about 50% of calories from carbohydrates, 30% from lipids, and 20% from protein. Patients received a list of the foods that were allowed on the diet and the foods to avoid, along with recommended portions and the possible combinations. They also received standard printed material and individual counseling at the beginning of the trial by family care physicians. Patients received dietary counseling at each clinic visit, but did not have any additional dietary reinforcement in order to assess the effect of sibutramine with minimal dietary counseling.

Sixty-nine patients started the trial medication, 22 patients in the sibutramine group finished the trial, and only nine patients in the placebo group finished the trial. Seven (20%) sibutramine patients withdrew their informed consent for lack of efficacy, as did 17 (50%) placebo patients. After three months of treatment, sibutramine patients had a weight loss of 7.07 [+ or -] 4.94 kg, with 67.6% of patients achieving the 5% goal. By the end of the six-month study, 76.5% of patients in the sibutramine group met the 5% goal, compared to 9.7% for the control group. The number of patients who reached the 10% goal of weight loss was 55.9% in the sibutramine group and none in the placebo group. Patients on sibutramine lost weight even in the last month of treatment.

Patients on sibutramine reported decreased appetite, increased satiety, and a better compliance with the diet from the first month of treatment on, and these remained constant up to the end of the trial. There were no differences in systolic or diastolic blood pressure between the two groups at any time. Sibutramine patients showed a small increase in heart rate during the first four months of treatment but returned to basal levels in the fifth and sixth month of treatment. In addition, electrocardiograms did not show significant variations between groups.

Based on this evidence, cardiovascular tolerance is not a serious limitation to extending the period of treatment.

In the sibutramine group, 23 patients reported 34 adverse events, most commonly upper respiratory tract infection and constipation. These adverse effects occurred primarily during the first two months of treatment. Three patients in this group withdrew when they experienced adverse events such as insomnia, anxiety, palpitations, dry mouth, and headache. In the placebo group, 16 patients had 21 adverse events.

Sibutramine effectively produced and maintained weight loss for up to six months, with significant changes in the waist circumference and in the waist/hip ratio. These results suggest that sibutramine covers most of the features of an ideal drag for the treatment of obesity, but additional trials are necessary to examine the effect on special groups of patients, as well as the effect on visceral fat. Taking into consideration the health risks of obesity in contrast to efficacy and tolerance of sibutramine, researchers feel that sibutramine can be used to complement a program of diet, exercise, and behavioral therapy.

G. Cuellar, A. Ruiz, M. Monsalve, A. Berber A. Six-Month Treatment of Obesity with Sibutramine 15 mg; a Double-Blind, Placebo-Controlled Monocenter Clinical Trial in a Hispanic Population. Obes Res 8:71-82 (2000) [Correspondence: Arturo Berber, Arzneimittelforschung BASF Pharma, La Candelaria 186, Colonia Atlantida, CP 04370, Mexico City DF, Mexico.]