Study summary · research use only
New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier?
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review surveys centrally active anorectic compounds in human clinical trials or approaching trials for obesity, describing proposed weight-loss mechanisms and side effects reported in the literature, evaluated against regulatory criteria used by the FDA and European Medicines Agency. It describes new targets from energy-balance research and a trend toward treatments targeting multiple mechanisms, either as single molecules such as tesofensine or as drug combinations such as qnexa, contrave, empatic, and pramlintide+metreleptin. The review also notes growing interest in peptide-based approaches to obesity as an alternative to developing new orally available small molecules, without reporting original trial data in this excerpt.
Abstract
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 mechanisms 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.
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