Current concepts in the pharmacological management of obesity

The pharmacological management of obesity has gained increasing attention a s new weight loss treatments are approved and a significant proportion of t he public strives to lose weight. Obesity is associated with a high mortali ty rate, multiple chronic medical conditions, and carries an enormous finan cial burden. Obesity is a multifactorial condition, most often due to an im balance in energy intake and expenditure. Despite the greater focus on management of obesity, weight loss remains a d ifficult goal to achieve. Obesity is a chronic medical condition that may r equire long term treatment, therefore the risks and benefits of all pharmac ological agents must be carefully considered. Noradrenergic, appetite suppr essants tie. phenylpropanolamine, phentermine result in weight loss but sti mulatory effects limit their use. The serotonergic agents (fenfluramine, de xfenfluramine) were effective weight loss drugs, but were voluntarily withd rawn from the US market last year because of cardiovascular and pulmonary c omplications. The combination noradrenegic/serotonergic agent sibutramine i s indicated for the management of obesity, particularly in the presence of other cardiovascular risk factors. Modest weight loss is achieved with sibu tramine, although weight gain is significant after discontinuation. In addi tion, long term safety data are not yet available. The thermogenic combinat ion of ephedrine plus caffeine is minimally effective, and adverse effects are usually transient. Other thermogenic agents, such as beta 3-agonists, a re still under investigation. Agents may alter digestion through lipase inhibition (orlistat) or fat subs titution (olestra). Orlistat decreases systemic absorption of dietary fat, decreasing body weight and cholesterol. Olestra is a fat substitute that ha s been incorporated into snack foods. Olestra substitution for dietary fat has not been studied as a weight loss strategy, although olestra has no cal oric value and may be beneficial. The use of orlistat and olestra may be li mited by gastrointestinal adverse effects. Finally, the manipulation of lep tin and neuropeptide Y are under investigation for the treatment of obesity . Pharmacological agents should be used as an aid to a structured diet and ex ercise regimen in the treatment of obesity. Weight loss agents may result i n initial weight loss, but sustained weight loss is not always achieved eve n with continuation of treatment. The effect of weight loss obtained while using pharmacotherapeutic agents on morbidity and mortality has not been es tablished. Therefore, diet and exercise should be the focus of any weight l oss programme. There is a continued need for safe and effective pharmacothe rapeutic agents for the treatment of obesity.