Sibutramine and energy balance.

Obesity develops from a combination of low energy expenditure and increased energy intake. The current treatment strategy aims at reducing energy intake by a low-fat, high-complex-carbohydrate diet and increasing energy expenditure by increased physical activity. In a major proportion of obese patients, however, this treatment is ineffective and does not produce a satisfactory long-term result. Among the risk factors for weight gain and for an unsuccessful diet-induced weight loss in obese patients is a low metabolic rate, which can be attributed in part to a low sympathetic nervous system (SNS) activity. The low SNS activity may also have an adverse effect on appetite control. Pharmacological enhancement of the SNS may have a role in the normalization of the autonomic control of the disturbed energy balance in obesity. In animal studies, sibutramine causes a negative fat balance and weight loss, by a dual mechanism of action. Sibutramine enhances satiety by a combined noradrenergic and serotonergic effect, thus decreasing food intake. In addition, sibutramine stimulates thermogenesis by activating the SNS. Recent studies have demonstrated that sibutramine also enhances satiety, stimulates thermogenesis and diminishes the weight-loss induced decline in energy expenditure in humans, so the dual effect on energy balance seems to be responsible for the efficient fat loss and weight maintenance found in clinical trials on obese patients. In conclusion, sibutramine can contribute to normalization of the disturbed energy balance in obesity, by enhancing satiety and by the stimulation of energy expenditure.