How Do They Work - Weight Loss Medications: Obesity

Content provided by the Faculty of the Harvard Medical School

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.

Last updated:	June 20, 2007