New agents in development for the management of obesity R. P. Vincent, 1 C. W. le Roux 1,2 Introduction The World Health Organization defines overweight as a body mass index (BMI) of at least 25 kg/m 2 and obesity as a BMI of at least 30 kg/m 2 . However, the health risks of increased body fat rise progressively above BMI levels of 20–22 kg/m 2 in all populations (1). More than 1.1 billion people in the world are estimated to be overweight, of which around 320 million are now calculated to be obese. It is esti- mated that up to 1.7 billion people may be exposed to weight-related health risk with more than 2.5 mil- lion deaths each year attributed to higher BMI, a fig- ure that is expected to double by 2030 (2). Obesity is a major cause of premature death in the UK (3) and may contribute to as high as 30,000 deaths a year in the UK. Its prevalence is on the rise worldwide in both adults and children. In the health survey of England and Wales 21% of men and 20% of women were found to be obese. The health consequences of obesity include heart disease, diabetes, hyperten- sion, hyperlipidaemia, osteoarthritis and sleep apnoea (4–8). The rising prevalence of obesity and obesity- related comorbidities also elevates healthcare costs, and reduces quality of life (9). The current pharma- ceutical treatment available to combat this epidemic remains limited. The National Institute for Health and Clinical Excellence in the UK recommends phar- macotherapy, in conjunction with lifestyle modifica- tion, for obese individuals (i.e. BMI of 30 kg/m 2 ) and for overweight persons with a BMI greater than 27 kg/m 2 accompanied by at least one comorbidity (10). The anti-obesity agents orlistat, sibutramine and rimonabant approved in Europe to treat obesity typically promotes no more than 5–10% loss of body weight. Hence at present the best therapeutic option available to obtain significant and sustained weight loss is bariatric surgery (11), as the average weight loss in clinical practice after 2 years for gastric band- ing is 20%, gastric bypass is 30% and biliopancreatic bypass is 35% (12). However, weight loss of 5–10% has been associated with improvements in cardiovas- cular risk profile and reduces the incidence of type 2 diabetes (13,14). The best opportunity to address the epidemic of obesity is to understand the underlying mechanisms of appetite control. Recently our understanding of neuroendocrine regulation of food intake and weight gain, especially regarding the role of gut hormones, has significantly increased. Applying this knowledge to help design medicines that can promote more substantial weight loss seems to be a promising con- cept to combat obesity in future. In this study we SUMMARY Obesity is fast becoming the major cause of premature death in the developed world. The rising prevalence of obesity and obesity-related comorbidities also ele- vates healthcare costs, and reduced quality of life. The National Institute of Clinical Excellence in the UK recommends pharmacotherapy, in conjunction with lifestyle modification, for obese individuals [i.e. body mass index (BMI) of 30 kg/m 2 ] and for overweight persons with a BMI greater than 27 kg/m 2 , accompanied by at least one comorbidity. However, the current pharmaceutical treatment available to combat this epidemic remains limited. We review the efficacy and pharmacology of the anti-obesity agents currently used in clinical practice as well as some of the potential agents in phase II and III trials. Review Criteria We searched MEDLINE, EMBASE and the Cochrane Library for articles published between January 2003 and March 2007, with the general search terms of ‘anti-obesity drugs’ and search terms specific to each individual drug and class of drug used in the treatment of obesity. Additionally, we selected relevant articles and comprehensive overviews from reference lists of identified studies. Message for the Clinic Obesity is a complex disease with limited treatment options at present. Several new treatments will become available in future, but without an understanding of the underlying physiology, success may be limited. 1 Department of Chemical Pathology, King’s College Hospital, London, UK 2 Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, UK Correspondence to: Dr CW le Roux, Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London W12 0NN, UK Tel.: 0208 8467077 Fax: 0208 8467007 Email: c.leroux@imperial.ac.uk Disclosures The authors have declared that they have no interests which might be perceived as posing a conflict or bias. doi: 10.1111/j.1742-1241.2007.01558.x REVIEW ARTICLE ª 2007 The Authors Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, December 2007, 61, 12, 2103–2112 2103