SIBUTRAMINE AND ENERGY-BALANCE

Obesity develops from a combination of low energy expenditure and incr eased energy intake. The current treatment strategy aims at reducing e nergy intake by a low-fat, high-complex-carbohydrate diet and increasi ng energy expenditure by increased physical activity. In a major propo rtion of obese patients, however, this treatment is ineffective and do es not produce a satisfactory long-term result. Among the risk factors for weight gain and for an unsuccessful diet-induced weight loss in o bese patients is a low metabolic rate, which can be attributed in part to a low sympathetic nervous system (SNS) activity. The low SNS activ ity may also have an adverse effect on appetite control. Pharmacologic al enhancement of the SNS may have a role in the normalization of the autonomic control of the disturbed energy balance in obesity. In anima l studies, sibutramine causes a negative fat balance and weight loss, by a dual mechanism of action. Sibutramine enhances satiety by a combi ned 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 s atiety, stimulates thermogenesis and diminishes the weight-loss induce d decline in energy expenditure in humans, so the dual effect on energ y balance seems to be responsible for the efficient fat loss and weigh t maintenance found in clinical trials on obese patients. In conclusio n, sibutramine can contribute to normalization of the disturbed energy balance in obesity, by enhancing satiety and by the stimulation of en ergy expenditure.