This chapter introduces the topic of obesity and the various methods that have been used to treat it, from lifestyle changes to surgery to weight loss drugs.

• In 2022, 42% of Americans were classified as obese, with obesity causing up to 14 years of lost life expectancy and costing the U.S. nearly $200 billion annually in medical expenses.
• The simplest way to treat obesity is through lifestyle and behavior changes, but these often do not produce significant or lasting weight loss.
• Bariatric surgery is the most effective intervention, but it comes with the complications of any surgery.
• Between these two extremes, weight loss drugs offer a potential solution, but their history is long and full of missteps and failed claims.

This chapter discusses various approaches to weight loss used in antiquity and the middle ages, including exercise, heat and massage, vomiting, and the use of various concoctions.

• Obesity has been recognized as a problem since antiquity, with treatments prescribed by doctors of the time including exercise, heat and massage, and the use of laxatives and purgatives.
• Roman doctors regularly advised obese individuals to vomit in the middle of the day, using a mixture of vinegar, salt, water, and hyssop plant.
• In 956, Sancho I of Leon, known as 'Sancho the Fat', was given a treatment called 'Theriaca', a mixture containing opium and other ingredients, which enabled him to lose enough weight to retake his throne.

This chapter provides an overview of modern weight loss drugs, discussing the general mechanisms by which they work and the specific substances that have been used.

• Modern weight loss drugs work by suppressing appetite, increasing energy expenditure, or interfering with the digestive system's ability to ingest fat.
• Substances used in these drugs include thyroid hormones, amphetamines and amphetamine-like substances, and drugs that interfere with fat absorption.
• These drugs have been associated with a wide range of side effects and health risks, leading to their eventual withdrawal from the market in many cases.

This chapter discusses the histories of specific weight loss drugs, including thyroid hormones, DNP, amphetamines, fenfluramine and phentermine (fen-phen), and others.

• Thyroid hormones were used to treat obesity in the late 19th century, but their use was limited by side effects similar to those of hyperthyroidism, including abnormal heart rhythm and possible heart failure.
• DNP, a substance used to make explosives, was found to cause weight loss by interfering with normal ATP energy production, but it could overheat the body and cause fatal intoxication.
• Amphetamines and amphetamine-like substances, including fenfluramine and phentermine (fen-phen), have been used for weight loss due to their appetite-suppressing effects, but have been associated with serious side effects and health risks.
• Other drugs, including aminorex, sibutramine, and CB-1 blockers, have also been used for weight loss, but have been linked to serious side effects and health risks, leading to their eventual withdrawal from the market.

This chapter concludes the video with a discussion on the future of weight loss drugs, noting the need for caution and realistic expectations given the long history of high-profile setbacks in this field.

• The history of weight loss drugs has been characterized by cycles of hype and hope followed by disappointment and withdrawal, underlining the need for caution and realistic expectations in the search for effective weight loss treatments.
• Most existing drugs have modest effects on weight loss and are associated with various side effects and health risks.
• The recent development of Glucagon-like Peptide 1 agonists (GLP-1s) offers hope for more effective weight loss treatments, but the history of weight loss drugs suggests the need for careful evaluation and monitoring of these new drugs.