At present, only two drugs are licensed and endorsed by the National Institute of Clinical Excellence (NICE) in the UK and the US FDA for long-term therapy against obesity: orlistat and sibutramine. Final appraisal documentation from NICE has also been published and recommends rimonabant if orlistat and sibutramine are contraindicated or no response is seen. Orlistat is an inhibitor of pancreatic and gastrointestinal lipases, preventing the absorption of dietary fat. As such, the gastrointestinal side effects of diarrhea and oily stools makes compliance with orlistat an issue. Sibutramine is a serotonin and noradrenaline reuptake inhibitor and its side effects include hypertension. Both drugs result in modest weight loss in clinical trials of between 4 and 8%. Rimonabant is a CB1 receptor antagonist that acts on several pathways within the brain to reduce weight (see ' Endocannabinoids' section). It is contraindicated in patients with a history of psychiatric illness. Work is currently underway to identify novel treatments that act within the CNS to control appetite. MC4-R agonists and drugs that modulate NPY[218,219] and serotonergic signaling are currently being investigated.
Expert Rev Endocrinol Metab. 2008;3(5):577-592. © 2008 Future Drugs Ltd.
Cite this: Hypothalamic Regulation of Appetite - Medscape - Sep 01, 2008.