on the Horizon
STEVEN B. HEYMSFIELD
After two decades during which development of drugs for weight loss appeared to slow, the last few years have brought renewed activity (see Chapter 99). This can be ascribed to several factors that have increased the market potential for new antiobesity treatments. The recognition that the prevalence of obesity is at unprecedented levels and still increasing, approval in the United States of only one new weight-loss drug in the period between 1970 and 1995 (dexfenfluramine), and its subsequent withdrawal because of previously unnoticed adverse effects, all influenced pharmaceutical development priorities. In addition, a spate of discoveries in the field of molecular biology, beginning with the cloning of the ob gene in 1994 and the identification of its protein product leptin, have revitalized drug development and the search for promising molecules. And finally, the growing recognition and acceptance that obesity is not a temporary predicament but one that requires long-term treatment has made the commercial potential of successful pharmacological treatment more attractive than ever.
One consequence has been a reevaluation by pharmaceutical companies of drugs currently approved or in development for other indications in which weight loss is a known side effect. The hope is to find a formulation or dosing regimen that will produce clinically significant weight loss. Weight losses are likely to be modest, but the medications vary in mechanisms of action and side-effect profiles, providing physicians and patients with choices.
Also, recent developments in molecular biology, along with the detailed exploration of animal and human genomes, have signaled a paradigm shift in identification of promising molecules. Specific endogenous proteins acting on specific sites can be studied for their effects. The effects are usually not specific or confined to simple disorders but have many seemingly diverse consequences. Still, the new techniques have enabled a more detailed and thorough investigation of mechanisms involved in weight regulation than was