An epidemic is sweeping through the developed world, threatening millions with disability and death. Is it the dreaded Ebola virus? No, it is obesity. ‘Epidemic’ may sound exaggerated, but the facts speak for themselves: 154 million people worldwide are obese—or more than 20% are over their ideal body weight—including more than 50% of all Americans. More disturbing is the prevalence of childhood obesity, which has jumped dramatically over the past 20 years and now accounts for a doubling in the incidence of diabetes, a 5-fold increase in sleep apnoea and a 3-fold increase in gall bladder disease. The World Health Organization and the US Surgeon General have already warned that obesity is a serious, life-threatening disease. Indeed, as a major risk factor for hypertension, stroke, heart disease, diabetes and possibly certain forms of cancer, obesity exacts a greater toll on health and healthcare costs than either smoking or drinking. In the USA alone, the direct medical costs of obesity-related diseases account for 6% of the nation’s entire health-care budget. Obesity is, in short, a great deal more than a ‘lifestyle’ or cosmetic problem.
This has not been lost on the pharmaceutical industry. Companies know that the worldwide market for an effective treatment for obesity is gargantuan: analysts estimate that an effective and safe drug could generate as much as US$26 billion per year in the USA alone. ‘It is probably the largest pharmaceutical market ever, and carries with it 27–30 dangerous co-morbidities,’ said Louis Tartaglia, Vice President of metabolic diseases at Millennium Pharmaceuticals (Cambridge, MA), who estimates the current annual worldwide market conservatively at US$10–15 billion. If one adds the patients who are obese and diabetic, the number soars even higher, as obesity and diabetes are linked diseases.
The sudden rise in obesity is mainly a result of lifestyle changes, particularly the ready availability of calorie-laden, refined food and a decrease in physical activity. ‘Genes have not changed in the past 50 years, but our eating and exercising habits have,’ said George Yancopoulos, Chief Scientific Officer and President of Regeneron Pharmaceuticals (Tarrytown, NY), one of many companies working on drugs to treat obesity. But it cannot be lifestyle alone. Certain ethnic groups have a higher prevalence of obesity, and the discovery of a number of genes that regulate fat storage point to an interaction between genetic and environmental factors.
Indeed, research on fat metabolism has made large strides forward over the last decade and has challenged some established views. ‘One of the most important advances in obesity research is the realisation that fat is an endocrine tissue,’ said Barbara Kahn, Professor of Endocrinology at Harvard University’s School of Medicine. Another step forward was the discovery of a number of peptides that function as central regulators of food intake and energy homeostasis. These...