New approaches to the pharmacological treatment of obesity Can they break through the efficacy barrier?

In this review we assess the range of centrally active anorectics that are either in human clinical trials or are likely to be so in the near future We describe their weight loss efficacy mode of action at both pharmacological and behavioural levels where understood together with the range of side effects that might be expected in clinical use We have however evaluated these compounds against the considerably more rigorous criteria that are now being used by the Federal Drugs Agency and European Medicines Agency to decide approvals and market withdrawals Several trends are evident Recent advances in the understanding of energy balance control have resulted in the exploitation of a number of new targets some of which have yielded promising data in clinical trials for weight loss A second major trend is derived from the hypothesis that improved weight loss efficacy over current therapy is most likely to emerge from treatments targeting multiple mechanism, of energy balance control This reasoning has led to the development of a number of new treatments for obesity where multiple mechanisms are targeted either by a single molecule such as tesofensine or through drug combinations such as qnexa contrave empatic and pramlintide + metreleptin Many of these approaches also utilise advances in formulation technology to widen safety margins Finally the practicality of peptide therapies for obesity has become better validated in recent studies and this may allow more rapid exploitation of novel targets rather than awaiting the development of orally available small molecules We conclude that novel more efficacious and better tolerated treatments for obesity may become available in the near future (C) 2010 Elsevier Inc All rights reserved