The Search for New Anti-Obesity Agents to Reduce Cardiometabolic Risk
Pp. 96-113 (18)
The global epidemic of obesity is rapidly accelerating in both industrialized and
developing countries, and has raised significant healthcare concerns worldwide. Obesity leads to
numerous co-morbidities, including cardiovascular diseases (CVD), type 2 diabetes (T2D),
hypertension, certain cancers, and sleep apnea. Obesity is considered an independent risk factor for
CVD, and is associated with dyslipidemia, hypertension, glucose intolerance and inflammatory
markers; all of which contribute to CV risk. The benefits of weight reduction to decrease
cardiometabolic risk are well-documented, yet long term weight loss has been difficult to achieve.
This has lead to intense efforts within the pharmaceutical industry to develop agents that result in
weight loss and prevent weight regain. Numerous strategies have been directed toward decreasing
food intake and/or increasing energy expenditure, yet this has met with limited success in
developing a safe and effective drug. This review summarizes the underlying mechanisms
contributing to CV risk in obesity, and discusses the targets that may result in novel
pharmacological agents that can sustain weight loss and reduce cardio-vascular morbidity and
Obesity, weight loss, adipose tissue, metabolic syndrome, cardiovascular disease.
Vice President Endocrine and Metabolic Diseases, Genzyme Corporation, 49 New York Ave., Framingham MA 01701-9322, USA.