Weight-loss medications

Diet drugs have gotten a lot of press. In June of 2007, an over-the counter version of the fat-blocking drug orlistat (Xenical) hit drug store shelves. Dubbed Alli, the drug works by blocking fat absorption in the intestines and must be taken before every fat-containing meal. Many physicians and patients were enthusiastic about rimonabant (Acomplia), a drug that works by blocking the same receptors in the brain that cause the "munchies" in marijuana users. Rimonabant is currently available in many European countries. But in 2007, a federal advisory committee recommended against the drug's approval in the US, citing concerns that rimonabant may leave people vulnerable to neurological and psychiatric problems—including a higher risk of suicide.

Other currently available prescription weight-loss drugs include those that suppress or regulate appetite by altering levels of brain chemicals — namely, sibutramine (Meridia) and phentermine (Adipex, Ionamin, others).

Of course, weight-loss drugs don't do the job by themselves. But for people whose health is at risk and who are struggling to reduce their weight through diet and exercise, drug therapy may increase the odds of success. Experts agree that weight-loss drugs, which all have side effects, are not for the mildly overweight or those who just want to lose a few pounds to improve their appearance.

Researchers have learned a lot about the biological causes of weight disorders, such as how genes influence the many systems that control weight. Weight-loss drugs can temporarily manipulate these systems. More than 200 drugs currently are in the testing phase.

Weight medications have a history of safety concerns. In the 1950s and 1960s, dieters took amphetamines to quell their appetites and boost their metabolisms — until it was discovered that the pills were addictive and caused paranoia. The combination of fenfluramine and phentermine, popularly known as fen-phen, was widely used in the mid-1990s, until fenfluramine and another drug, dexfenfluramine, were linked to heart valve disease and withdrawn from the market. (Phentermine, the weaker but safe half of fen-phen, is still used.)

Until sibutramine was approved in 1997 for long-term use in obesity, the FDA had required that most such medications be prescribed for no longer than three months. Both sibutramine and orlistat are approved for use up to one year, but physicians may prescribe them for longer. Sibutramine is considered effective and safe for up to two years, although it can increase blood pressure and thus requires monitoring. Orlistat, which inhibits the body's ability to absorb fats, can interfere with the absorption of fat-soluble vitamins. Moreover, little is known about how safe it is to use weight-loss drugs for more than two years.

On the other hand, these medications have a role to play in medical treatment, especially now that obesity is recognized as a metabolic disease and not a failure of motivation or willpower, as was once thought. Clinicians are finding that obesity, like other chronic conditions, is often easier to manage with judicious, long-term medication use.

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Who should take them?

One way to minimize the risks of these drugs is to prescribe them only for people who need them for health reasons: those who have obesity-related conditions such as type 2 diabetes or hypertension, or those at high risk for developing such disorders. Guidelines issued by the National Institutes of Health (NIH) advise that weight-loss drugs be given only to people with a BMI of 30 or more, or — in the case of those with weight-related health problems — a BMI of 27 or more. The use of diet drugs by people with lower BMIs is likely to pose more risks than benefits.

Be aware that weight-loss drugs aren't effective for everyone. Clinical guidelines suggest that if a person hasn't lost at least a pound a week in the first month on a weight-loss medication, she or he is unlikely to benefit from the drug. A drug that helps one person may be no better than a placebo for someone else. For example, people who overeat because of stress, bad habits, or emotional issues may benefit less from appetite suppressants than do people who overeat because of hunger. For them, psychotherapy or behavioral therapy may be a more appropriate first step.

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How should they be taken?

The NIH guidelines make clear that weight-loss drugs should be used only in combination with lifestyle modifications. To lose weight over the long term, you need to recognize and change the behaviors that led to the weight gain. Otherwise, any weight you lose is likely to return.

Drug therapy works better when it's paired with an overall program of lifestyle change. A study published in 2005 in the New England Journal of Medicine showed that after one year, Meridia users who participated in a comprehensive counseling program that promoted a low-calorie diet and 30-minute daily walks lost twice as much weight as subjects who received counseling alone or Meridia alone.

Among its most important benefits, counseling can help establish realistic goals. The idea behind using weight-loss medications is to improve health and reduce disease risk, not to achieve an ideal body weight. A 5%–10% reduction in weight over time is one common goal. But even more modest weight loss helps. One study of women with obesity demonstrated that those who intentionally lost any amount of weight experienced a 40%–50% decrease in death from obesity-related cancers and a 30%–40% decline in death from type 2 diabetes.

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How do they work?

The prescription weight-loss medications on the market as of summer 2006 generally fall into three categories. (See Table 4 for details on each of these drugs.)

Noradrenergic agents. These medications increase levels of norepinephrine (also known as noradrenaline), a brain chemical that helps regulate appetite and resting energy expenditure (the amount of calories the body needs during inactivity). Phentermine is the safest. On average, people taking phentermine lose 2–13 pounds over a 6-month period. After that, weight loss tends to level off, as it does with other diet drugs. These drugs have several side effects; patients should be carefully re-evaluated after three months before continuing to take them.

Serotonin-norepinephrine reuptake inhibitors. The only weight-loss drug in this category is sibutramine (Meridia). It works by increasing the availability of serotonin and norepinephrine, brain chemicals that make people feel full and stimulate resting energy expenditure. Initial weight loss with sibutramine predicts long-term response to the drug: One study showed that people who lost more than 4 pounds in the first month were more likely to lose 10% of their body weight after 1 year than those who lost less weight initially.

Lipase inhibitor. The only lipase inhibitor currently available in the United States is orlistat (Xenical), which works by blocking the action of lipase, an enzyme released by the pancreas and intestine that helps digest dietary fat. It works about as well as the other medications, helping people lose about 5%–8% of their body weight.

Other medications that are not specifically approved for weight loss cause some people to shed pounds. They include certain drugs used to treat depression, seizures, and diabetes.

Antidepressants. Certain antidepressant drugs, particularly bupropion (Wellbutrin), are sometimes prescribed on a short-term basis because they've been found to help some people lose weight. Most doctors prescribe this medication only for people who have mild to moderate obesity who also have symptoms of depression. Short-term studies showed that people taking bupropion lost about 4%–5% of their weight, compared with less than 2% in people taking placebos.

Antiseizure drugs. Two medications used to treat seizure disorders, topiramate (Topamax) and zonisamide (Zonegran), are being studied as possible treatments for obesity. But topiramate's side effects (confusion and other thinking problems) make it unacceptable for most people. Zonisamide caused a 6% loss of body weight, compared with 1% in a control group, in one study. The main side effect was fatigue. But further, longer studies are needed before this medication is widely recommended.

Diabetes drugs. Most medications used to treat people with type 2 diabetes tend to cause weight gain, but two, metformin (Glucophage and others) and exenatide (Byetta), have the opposite effect for some people. In the Diabetes Prevention Program study, people taking metformin lost an average of 4% of their body weight over one to two years. Exenatide has similar effects, although it must be injected and may cause gastrointestinal problems. Both drugs should be taken only by people who have (or are at a high risk for developing) type 2 diabetes and are being closely monitored by a doctor.

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Review Date: 2006-09-01

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