For people with obesity, weight loss drugs can be a helpful part of treatment
By R. Morgan Griffin
WebMD Weight Loss Clinic - Feature
Reviewed By Charlotte E. Grayson, MD
To many people, any weight loss drug seems like it must be a scam. It's just too good to be true, as plausible as an effective bust-enlargement cream or Home Alchemy Kit.
However, weight loss drugs -- like Xenical and Meridia -- do exist. They also work. And pharmaceutical companies across the globe are industriously working on more. They're not for cosmetic use, so mildly overweight people fretting about bathing suit season shouldn't apply. Their effects are also modest, usually resulting in a loss of no more than 10% of a person's body weight. Contrary to some hopes, they don't replace diet and exercise; weight loss drugs only work in conjunction with lifestyle changes.
Why Use a Weight Loss Drug?
Many people, including doctors, have a strong aversion to using weight loss drugs to treat obesity, according to Holly Wyatt, MD, an endocrinologist at the University of Colorado Health Sciences Center. The longstanding wisdom was that obesity resulted from a failure of willpower. If only people would just stop eating so much and get off the couch, no one would be obese. So why bother with drugs?
But that simple way of thinking is increasingly under fire from experts. It isn't the whole story.
"Lifestyle is a big factor in why people gain weight," Wyatt tells WebMD. "But there's a definitely a genetic and a physiologic reason, too. Because of differences in physiology, some people will just have a harder time losing and maintaining weight than others."
George A. Bray, MD, professor of medicine at Louisiana State University, agrees that the traditional view of obesity -- as essentially a moral failing -- is wrong.
"Are people who are massively overweight because they lack [the hormone] leptin 'weak-willed'?" asks Bray. "No, and, in fact, some kind of neurochemical derangement probably underlies most obesity."
"It's cruel and hurtful to categorize overweight and obese Americans as 'lazy' or 'weak-willed,'" he says, "and to conclude that all they need to do is just push themselves away from the table."
Obesity as a Disease
Obesity is a killer. So is it enough for a doctor to tell a chronically obese person to lose weight and leave it at that? Wyatt and Bray both point out that we routinely use medication for other conditions that can be controlled by changes in diet and exercise.
For instance, diabetes and high blood pressure can both be helped substantially by changes in your lifestyle. But doctors still prescribe medication for both conditions. It would be highly unlikely for your doctor to refuse to give you diabetes medicine simply because you could control the disease with more exercise and a stricter diet but don't. Everyone knows that permanent lifestyle changes are very hard to make, Wyatt says.
"We don't punish diabetics or people with high blood pressure by withholding medicine," says Wyatt. "So why should we punish people with obesity? If you have a medication that will make it easier for people to lose weight, why not use it?"
Wyatt and Bray both stress that anyone who needs to lose weight should try lifestyle changes first. But for those who can't seem to do it with exercise and diet alone, weight loss drugs could help.
The Causes of Obesity
At the most basic level, your weight is determined by the balance between the amount of energy you take in and the amount you expend -- the food you eat and the calories you burn. If you burn more calories than you eat, you'll lose weight; if you eat more than you burn, you'll gain.
However, while that equation is still roughly true, researchers have found that it's a lot more complicated. The body has many complex and interacting mechanisms that help regulate your weight.
One of them is the hormone leptin, which is secreted by fat cells. Your brain detects the amount of leptin in your system and uses it as a kind of barometer. Not enough leptin presumably means that you need more food; enough leptin is a sign that you've eaten as much as you need, and your brain triggers feelings of fullness. The problem is that many obese people are leptin-resistant. Their brains don't correctly detect the amount of leptin in the system, "thinking" that the level is lower than it really is. As a result, a leptin-resistant person will keep feeling hungry after a person with normal leptin levels would feel full.
Leptin is only one of many different mechanisms that regulate weight. Any kind of abnormality in these systems could make it harder for a person to lose weight and keep it off.
Weight and Genetics
Wyatt observes that, from an evolutionary standpoint, there's an advantage to building up excess fat. For most of human history, people were subject to periodic famines. Those who retained excess fat might have been more likely to survive a famine than those who didn't. The problem is that this evolutionary adaptation -- that may have saved the lives of our ancient ancestors during difficult times -- is hurting us now.
This is not to say that having a predisposition to being obese means you will be obese. The fact that Americans are heavier now than they were a generation ago proves that genes aren't the whole story. It's the changes in our environment that have made the biggest difference, Wyatt says.
A genetic predisposition toward obesity will only come into play when the environment is right. Getting obese was unlikely when our ancestors were eking out an existence on the savannah. But when we live in a society of sedentary jobs, sedentary entertainment, and cheap, plentiful and colossally caloric meals available at countless locations near you, that genetic predisposition can make a big difference.
How Do Medications Help?
The two drugs currently approved by the FDA to treat long-term obesity are Xenical and Meridia. They work in different ways. Meridia affects certain chemicals in the brain and makes people feel full without eating as much.
Xenical works very differently. It isn't absorbed by the system. Instead, it binds to fat cells in the gastrointestinal tract and prevents them from being absorbed, just like the ingredient Olestra used in some low-fat foods. The usual dose can reduce the amount of fat that's absorbed by about 30%.
The FDA has approved the use of weight loss drugs in people with a BMI of 30 or as low as 27 in some people who have illnesses related to obesity, like diabetes or heart disease. The BMI is a measurement based on height and weight. According to the National Institutes of Health, a normal BMI ranges from 18.5 to 24.9, 25-29.9 is overweight, and anything above that is obese.
Other drugs may be helpful in some cases. For instance, Wyatt has had good success with the generic drug phentermine, which suppresses appetite like Meridia. However, the FDA has not approved phentermine for long-term use. That's not because it was found unsafe -- it's just that no one has funded a study of its long-term effectiveness. And because studies are expensive, no pharmaceutical company will want to spend the money testing a generic drug that it doesn't exclusively own.
As much as people may dream of the pill that lets them lose weight without diet or exercise -- the claim of countless hucksters and infomercials -- none of these drugs works that way. Studies have shown that these drugs really only work in conjunction with lifestyle changes.
The amount of weight that people lose on weight loss drugs varies: Some people have great success and some don't. On average, people don't lose more than 10% of their baseline weight -- that's a 20-pound weight loss for a person who is 200 pounds. Generally, people lose the most weight in the first three to six months on the drugs and then plateau.
A 10% weight loss may not sound like a lot. But experts stress that modest weight loss -- even 5% -- can make a big difference in your risk of developing disease. Many studies have shown the effectiveness of weight loss drugs in reducing health risks. For instance, a recently published study of Xenical found that it could cut the risk of type 2 diabetes by 37%.
How Long Would Someone Need to Use Them?
Studies have shown that if a person on one of these medications doesn't lose 4 pounds in the first four weeks, then it can probably be stopped; it's unlikely that the drug is going to work. If someone does have success with a drug, it should probably be taken long term. Weight loss drugs are not a quick fix. Instead, they're more like medication for high blood pressure or diabetes, Wyatt says. Obesity really is a chronic disease.
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"The physiology that causes someone to become obese doesn't go away," says Wyatt. Stopping the drugs usually means that the weight will come back. And losing the weight doesn't matter as much as keeping it off. If you lost 20 pounds but regained it all within the year, it's not going to help all that much.
Long-term treatment doesn't mean that people will necessarily be taking the same weight loss drug every day for the rest of their lives. Instead, it's possible that someone might switch between Xenical, Meridia, or other drugs.
It may also be possible for people to take breaks in treatment. "Weight isn't like blood pressure," says Wyatt. "If you stop taking your blood pressure medication, it goes up within a few days. Regaining weight takes longer." So far, studies have not shown any advantages to using weight loss drugs periodically. But as researchers learn more about how to best use these medications, it may be a possible form of treatment in the future, Wyatt says.Are They Safe?
One of the biggest concerns for anyone considering a weight loss drug is its safety. The fear is understandable. The much-touted combination of weight loss drugs called fen-phen -- phentermine and another drug, fenfluramine -- was found to cause dangerous damage to the heart valves in some people. As a result, both fenfluramine and Redux, another similar weight loss drug, were pulled from the shelves in 1997. On its own, phentermine is considered safe and still used.
Being cautious about any weight loss drug is good policy. None of these drugs have been around that long, and so we can't be sure of their long-term effects.
That said, the safety records for both Xenical and Meridia are good and the risk of side effects are low. Meridia can cause headaches, dry mouth, and a rise in the pulse and blood pressure.
Xenical can cause gastrointestinal side effects, such as spotting, an urgent need to go to the bathroom, and an increased number of bowel movements. These side effects tend to fade over time, and are aggravated by eating a high-fat meal. Xenical can also reduce the amount of vitamins that your body absorbs, so you may need to take a multivitamin to compensate.
But researchers have found no side effects like those of fen-phen.
"Any medication carries risk," says Wyatt. "But at this point, I think that [Xenical and Meridia] are as safe as any other medication that we routinely prescribe." In fact, because of the fen-phen debacle, she thinks that weight loss drugs may be held to an even higher level of safety than other types of medicine.
Wyatt also observes that the very small risks of these drugs have to be compared to the real risks of obesity, such as high blood pressure, diabetes, stroke and heart disease. For people who are very obese, another way to frame the choice could be to compare the low risks of weight loss drugs with the higher risks of bariatric surgery, often called stomach stapling.
The Future of Weight Loss Medications
Many doctors and researchers hope the weight loss drugs of the next decade will make Xenical and Meridia look crude. As researchers learn more and more about the complex set of mechanisms that regulate our weight, the drugs we use will become increasingly sophisticated.
A number of medications are now in various stages of development with more specific targets. Many are designed to affect some of the hormones -- such as leptin -- that play a role in appetite and weight regulation.
Wyatt has modest hopes for new weight loss drugs in the immediate future. "I don't see any of the new drugs as obvious blockbusters," she says. She points out that we may need combinations of new drugs to have a substantial effect. The problem is that there are so many different mechanisms that affect our weight that just targeting one may not be enough.
Bray says we'll just have to wait. "Until we get the data from the long-term trials of these drugs," he tells WebMD, "we just won't know how safe or effective they are."
"We're really just in the early stages of using weight loss drugs," says Wyatt. "It's just like when we first began to use drugs for high blood pressure, and they didn't work all that well and caused a lot of side effects. But we'll get better drugs, and as we do, doctors will use them more and more."
So barring some unforeseen breakthrough, weight loss drugs are not going to be "the answer" to obesity any time soon. But along with diet and exercise, they can be an important part of the solution.
Published May 6, 2004
SOURCES: George A. Bray, MD, Boyd Professor at Louisiana State University; professor of medicine at the LSU Medical Center. Holly R. Wyatt, MD, assistant professor of medicine, division of endocrinology, University of Colorado Health Sciences Center, Denver. Wyatt, H. Postgraduate Medicine, January, 2004; vol. 115. National Institute of Diabetes and Digestive and Kidney Diseases. National Center for Biotechnology Information. WebMD Medical News: Xenical May Cut Type 2 Diabetes Risk. WebMD Medical News: New Weight loss drugs Pass First Tests. WebMD Medical News: "FDA Approves Weight Loss Pill for Teens." WebMD Scientific American Medicine, Endocrinology: X. "Obesity." WebMD Medical News: "Next Miracle Weight-Loss Drug?" WebMD Medical News: "Growth Hormone May Be Fat Fighter." WebMD Medical News: "A Hormone That Helps You Feel Full."
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