## 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.125 Nearly 68% of Americans are overweight (body mass index {BMI}, 25–29.9) and 35% are obese (BMI >30 kg/m2).53,123 Even more alarming, the incidence of obesity in children between the ages of 6 and 19 years has tripled in the past 30 years.12,124 As many as 17% of children aged 2 to 19 years of age are obese, and 31% of children are overweight.12,123 There are conflicting data as to the exact number of deaths attributed to obesity annually; however, all of the studies agree that obesity results in excess mortality.53,54 In 2009, the Centers for Disease Control and Prevention reported greater than 110,000 deaths due to obesity in the United States. The cost of obesity is staggering and is reported to be upward of $147 billion.27 Obesity is linked to numerous health risks, including type 2 diabetes, hypertension, coronary heart disease,12,24 metabolic syndrome,170 and low back pain.148 Obesity is considered a leading preventable health risk, second only to cigarette smoking. Genetic links including particular gene polymorphisms have been identified and are being pursued.116 Americans spend upward of$60 billion per year on weight loss therapies and modalities. Pharmacologic interventions typically result in a 5% to 10% weight loss, although a return to baseline upon drug cessation is common.46 Surgical interventions consistently achieve substantial weight loss, causing up to a 30% reduction in weight, but they are not without complications.2,20

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.79

Currently, medicinal weight loss therapies (Table 42–1) are available as prescription medications (lorcaserin, phentermine, phentermine/­topiramate), 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 and some with serious toxicity.

TABLE 42–1.Available Weight Loss Xenobiotics

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