## INTRODUCTION AND HISTORY

Obesity is a worldwide epidemic, and the United States has the largest proportion of a national population of overweight and obese individuals. According to the World Health Organization, 67.3% of the US population older than 18 years of age has a body mass index (BMI) of 25 or greater. The only country that has a larger proportion is the United Arab Emirates.135 The majority of countries in the world have demonstrated a doubling to quadrupling of those with obesity in the past 30 years.61 Some estimates predict that nearly 38% of the world’s adult population will be overweight and 20% will be obese by 2030.61,66 Even more alarming, the incidence of obesity in children between the ages of 6 and 19 years has tripled in the past 30 years. In one systematic review, there was a strong association between childhood obesity and adult obesity. Eighty percent of obese adolescents were obese into adulthood.117 Although there are conflicting data, it is clear that obesity results in excess mortality.39,40 In 2009, the Centers for Disease Control and Prevention reported more than 110,000 deaths caused by obesity in the United States. Mortality is a proven increase for every 5 kg/m2 higher than a BMI of greater than 25 kg/m2 with a reduction of median survival of 8 to 10 years in those with a BMI between 40 and 45 kg/m2.103 Obesity is linked to numerous health risks, including type 2 diabetes, hypertension, coronary heart disease,10,18 metabolic syndrome,133 fatty liver, and low back pain.114 Obesity is considered a leading preventable health risk, second only to cigarette smoking with a large economic impact costing upward of $147 billion annually.21 Americans spend upward of$60 billion per year on weight loss therapies. Pharmacologic interventions typically result in a 5% to 10% weight loss, although a return to baseline upon drug cessation is common.32,109 Surgical interventions consistently achieve substantial weight loss, causing up to a 30% reduction in weight, but they are associated with numerous and varied complications.26

One of the earliest accounts of weight loss therapy dates back to 10th century Spain. King Sancho I, who was obese, underwent successful treatment with a “theriaca” thought to contain plants and possibly opioids, administered with wine and oil. In addition, he was closely supervised and treated by a physician.60

Weight loss xenobiotics (Table 40–1) are available as prescription medications (lorcaserin, phentermine, phentermine/topiramate, bupropion/naltrexone, phendimetrazine, orlistat, and liraglutide), nonprescription dietary supplements (Citrus aurantium, chitosan, Garcinia cambogia, caffeine), and nonprescription diet aids (orlistat). Numerous other prescription medications, including thyroid medications and metformin, have been used on an off-label basis for weight loss. Numerous xenobiotics are promoted as weight loss aids, many with no proven efficacy ...

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