Obesity is a growing problem worldwide, with serious health and qualityof-life implications.

Dietary and behavioral changes offer only limited help; although some people benefit from antiobesity drugs, expectations are often unrealistic.

The effectiveness of current treatments is limited; for the morbidly obese, surgery is the most effective option, although it is not risk-free.

Efforts to foster weight loss are countered by the body’s inherent need to preserve weight. Considerable progress has been made in identifying new means of treating obesity, particularly those that suppress appetite or restrict fat absorption.

The extremely complexity of the body’s energy system means that altering one part affects others, as well as other biological systems.

The development of new drugs should focus on helping patients eat less and better utilize what they eat; thus far, drugs that stimulate the use of existing fat stores are in the early stages of development.

Pharmaceutical agents will not solve the obesity problem by themselves; lifestyle adjustments will likely always be necessary.

For the immediate future, the most effective treatment is likely to be a combination of drug and behavioral therapy, along with changes in diet, rest, and exercise.

Download Obesity and New Pharmaceutical Approaches

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Steven Marks
American Council on Science and Health

CONTENTS
CHAPTER 1
Executive Summary
CHAPTER 2
Introduction
CHAPTER 3
What’s Under the Hood: How the Body Regulates the
Balance Between Food Intake and Energy Expenditure
CHAPTER 4
Current Treatments: How Effective Are They?
CHAPTER 5
New Approaches: Putting the Central and Peripheral
Mechanisms to Work
CHAPTER 6
Central Targets: The Role of the Hypothalamus
a. The Serotonin System: A Safer Redux?
b. Gut Hormones: Ensuring Fuel for the Short Trip
CHAPTER 7
Peripheral Mechanisms: Energy Expenditure
a. Metabolism
b. Fat Storage
CHAPTER 8
Toward the Future
CHAPTER 9
Conclusion
ACKNOWLEDGMENTS
REFERENCES

INTRODUCTION
The endocrinologist David Ludwig calls his patients, the seven-member G family, “a microcosm of 21st-century America.”

One of the parents is overweight and the other is obese, wrote the Harvard Medical School professor and director of the Optimal Weight for Life Clinic (Ludwig 2007). All five of the children are even more severely obese, and although they are still young, they already face the prospect of lives limited by chronic medical
problems. One of the youngsters shows the first signs of fatty liver, while another has high blood pressure.

Three have marked insulin resistance, the first sign of type-2 diabetes; four have abnormal cholesterol profiles, and two complain of orthopedic problems. The children all express serious emotional distress, stemming from their obesity. Were the G family unusual, their health problems could be written off as medical curiosities. Unfortunately, families like that of Mr. and Mrs. G and their children are becoming all too common in industrialized nations around the world.

Today, about 66% of all Americans are overweight or obese (Ogden 2006). Researchers from the Centers for Disease Control and Prevention (CDC) report that since 1970, the number of overweight children and adolescents between the ages of 6 and 19 years has tripled, meaning that more than 9 million young Americans (or nearly onein-five) are at risk for a wide range of obesity-related problems, including diabetes, hypertension, high cholesterol, coronary artery disease, respiratory problems, sleep apnea, gallbladder disease, osteoarthritis, and several forms of cancer (Cooke 2006).

These trends suggest that the current generation of Americans may be the first in the past 200 yeas to have a shorter life expectancy than their parents had, according to physicians at the University of Illinois Medical Center in Chicago (Olshansky 2005). This is hardly the definition of progress.

In addition to the health consequences, obesity also entails substantial economic and social costs. An obese worker costs his employer an estimated $2,500 per year in added medical expenses and lost productivity, according to studies from RTI International and the CDC.

Overall, business and industry pay a hefty price for obesity:$13 billion a year, estimates the Washington, DC-based National Business Group on Health, a health policy group comprising the nation’s largest corporations (Harper 2007).

Obese people themselves are often stigmatized. Documented cases of discrimination extend to employment, education, and healthcare. There have also been suggestions of bias in adoption proceedings, jury selection, housing, and other areas of public life, according to Yale University investigators (Puhl 2001).

Obesity is now the nation’s second-biggest public health problem, right after smoking. Although lifestyle changes, most notably dietary adjustments and increased physical activity, can help people lose weight and stave off obesity, many find it difficult to comply with such weight-loss regimens. Shedding surplus pounds is frequently a struggle, but for many people, it's a battle they are genetically programmed to lose. (Later on, we’ll learn just why this is so.) For this reason, a great deal of interest – and hope – rests on the potential effectiveness of pharmaceutical therapies for obesity.

Americans currently spend more than $33 billion a year on weight-loss treatments (BW 2008), ranging from prescription drugs to diet programs and nutritional supplements. Not all such treatments are credible (see “Buyer Beware” sidebar in Chapter 4), and the results can be disappointing for even those treatments that have value. Nonetheless, the pharmaceutical industry has invested enormous capital in the search for effective and safe weight-loss drugs that target the body’s intricate energy-regulation mechanisms. The research and development continues today.

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