Endocrine Abstracts (2004) 7 S9

Current approaches, future therapies

N Finer

Wellcome Trust CRF, Cambridge University, Cambridge,UK.

Preventing obesity is an increasing focus for public health and social policy, but effective treatment for those who are already obese and those who will inevitably fail even the best preventative programmes is needed. The banality that both energy intake and expenditure can be modified by voluntary behaviour changes belies the observation that obese people have at not at losing weight but at maintaining weight loss. The objectives of obesity management to improve health status are achieved with modest loss of 5-10%. Meeting patient expectations, as well as quality of life and psychological benefit, usually requires far greater loss. Lifestyle therapies form, and will continue to form, the basis of treatment since they address nutritional improvement (not just energy reduction), metabolic 'fitness' from increased physical fitness, and psychological needs.

Pharmacotherapy is currently limited to sibutramine (predominately affecting food intake) and orlistat (diminishing energy intake by decreasing nutrient absorption). Continued medication largely maintains weight loss for 3-4 years, with improvement of both surrogate and hard (e.g. diabetes prevention/delay) clinical endpoints. Predicting and identifying drug-responders would be clinically useful and provide insights into obesity aetiology. Cannabinoid receptor antagonists (e.g. rimonobant in Phase III clinical development) look promising and may have desirable effects independent of weight loss. Atypical anticonvulsants (zonisamide, topiramate) produce excellent weight loss, but may be limited by unwanted CNS effects. Elucidating peripheral and central inputs to the hypothalamic control of energy balance provides many new drug targets, but none are likely to be licensed within the next decade.

The rapid advance in minimally invasive surgical procedures to restrict intake, modify absorption, or later gut-brain physiology is lowering the weight and age thresholds for consideration of bariatric surgery and thereby raising the expectations of drug treatment.

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