Weight Loss Drugs: Pros and Cons of 5 Approved Prescriptions

A heavy woman stands back-to-back with a thin woman.
(Image credit: hartphotography/Shutterstock)

For most people, the prescription for weight loss is pretty basic: Eat less, move more. In recent years, however, new drugs to combat obesity have moved onto the market.

A new breakdown of these options, released today (Aug. 18) in the Journal of the American Medical Association (JAMA), highlights the promise and perils of each of these medications, which range from appetite suppressors to stimulants.

None of these drugs are a magic bullet. They all must be accompanied by following a healthful diet and exercising, and their effects on the scale are moderate compared with the dramatic weight loss seen in people who undergo gastric bypass surgery, said Dr. Jill Jin, a general internist at the Northwestern Medical Group in Chicago, who wrote the article. However, Jin told Live Science, these medications can benefit certain patients.

"There is benefit in even losing 5 percent to 10 percent of your body weight," Jin said. "You can see changes in blood pressure, in average blood sugar levels, in cholesterol."

Who can benefit from weight loss drugs?

Weight loss drugs aren't for everyone. According to guidelines released by the Endocrine Society in January 2015, these pharmaceuticals are appropriate only for people who qualify as obese, meaning they have a body mass index (BMI) of 30 or higher. Drugs might also be helpful for people who are merely overweight (with a BMI of 27 or higher) but who also have health conditions brought on by their extra pounds, such as high blood pressure or heart disease.

The benefit of these medications is that they help move weight loss along more quickly than diet and exercise alone, thus encouraging patients to stick to their lifestyle changes, Jin said.  [7 Biggest Diet Myths]

"It's a good mental effect," she said.

Patients who are prescribed these drugs are monitored closely. If they don't lose at least 5 percent of their body weight after three months of use, they should discontinue using the drugs, according to the Endocrine Society. Weight loss benefits continue only as long as the drugs are taken, so users also need to develop healthy habits.

"Because all medications inherently have more risks than diet and exercise do, pharmacologic therapy should be used only in patients in whom the benefit justifies the risk," the society concluded.

What drugs are available?

As American waistlines have expanded, pharmaceutical companies have been searching for drugs that can shrink those waistlines again. Still, only five drugs (or drug combinations) have been approved by the Food and Drug Administration for the long-term treatment of obesity. Here's a brief rundown of each:

Orlistat – Now available over-the-counter or as a prescription, orlistat was one of the first drugs in the weight-loss arsenal. It was first approved in 1999 by the FDA for use with a prescription, and then in 2007, it was approved for over-the-counter use. The drug is sold under the brand name Xenical as a prescription and Alli as an over-the-counter drug.

Orlistat is meant to treat obesity in conjunction with a low-fat, low-calorie diet, according to the FDA. The drug is a lipase inhibitor, meaning it works to prevent the action of a pancreatic enzyme called lipase, which breaks down fat in the small intestine. Thus, taking orlistat with each meal prevents the absorption of all the fat from the food into the body.

The most common side effects of orlistat relate to the extra fat being excreted instead of absorbed: gassiness, oily bowel movements and other bowel-related changes. Reports of severe liver damage in about a dozen people who used orlistat prompted a new warning label in 2010, though the FDA could not confirm that the drug caused the damage. People who take the drug should watch for signs of liver malfunction such as yellow skin or eyes, itching, loss of appetite, brown urine or yellowish stool.

A 2004 review of research published in the journal Obesity Reviews found that orlistat is effective in reducing weight in obese patients, but caused more gastrointestinal distress than a placebo. However, the weight loss is likely to be modest. According to the Mayo Clinic, a 2014 review found that people who dieted, exercised and took Alli for at least a year lost about 5.5 pounds (2.5 kilograms) more on average than those who dieted and exercised alone.

Lorcaserin – This drug acts on serotonin receptors in the brain to promote feelings of fullness, thus encouraging users to eat less. Approved in 2012, lorcaserin was the first weight-loss drug to get an FDA nod since orlistat.

According to the FDA, the drug (combined with diet and exercise) was associated with an average weight loss of 3 to 3.7 percent more than a placebo. In patients without Type 2 diabetes, 38 percent using the drug lost 5 percent or more of their body weight, which is the clinical standard for a successful obesity treatment. Among patients who used diet and exercise alone, 23 percent reached that level of weight loss.

Because lorcaserin affects serotonin receptors, it can't be used alongside other drugs with the same target, such as selective serotonin reuptake inhibitors (SSRIs), which are used to treat depression. The drug is not approved for pregnant women and can cause side effects such as drowsiness, headache and constipation. [9 Meal Schedules: When to Eat to Lose Weight]

Sold under the brand name Belviq, lorcaserin is taken by mouth, usually twice a day.

Phentermine + topiramate – Also approved in 2012, this drug combination is sold under the brand name Qsymia. Phentermine is a stimulant that decreases appetite; topiramate is an anti-seizure and migraine drug that also decreases appetite and causes feelings of fullness.

The drug combination can cause a birth defect called cleft palate in developing fetuses, so women of childbearing age taking it must use birth control and take a pregnancy test monthly. Another rare but serious side effect is the development of suicidal thoughts. According to the National Institutes of Health, about 1 in 500 people who take anti-seizure drugs like topiramate develop suicidal thoughts or behaviors.

Like all other approved weight-loss drugs, the combination of phentermine and topiramate is meant to be used with a diet and exercise routine. In a clinical trial, patients who took this drug combo lost an average of 9 percent of their body weight, compared with 1.5 percent in patients who took a placebo, according to a 2013 paper in the journal Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. Two follow-up trials returned similar results for up to 2 years of use.

Bupropion+naltrexone – Sold under the brand name Contrave, this drug combination first came into the spotlight in 2011. It was rejected by the FDA because of concerns about its long-term effects on the heart and cardiovascular system. In 2014, however, the agency gave Contrave the go-ahead — with the caveat that it will still be under scrutiny to ensure its cardiovascular safety.

The drug also has a black box warning — the strictest of the FDA warning labels — because bupropion is associated with an increased risk of suicidal thoughts. The drug was previously approved as a smoking cessation aid and to treat depression. Naltrexone had been used to treat alcohol and opioid addiction. Doctors aren't entirely sure how the drug combination works to promote weight loss. According to a 2011 paper in the journal Pharmacy & Therapeutics, the drug's most likely targets are the hypothalamus, an almond-size region deep in the brain that controls hunger, and the mesolimbic reward system, a brain circuit that is involved in any rewarding activity, including eating.

In one trial, 42 percent of patients without Type 2 diabetes who took Contrave along with a diet and exercise routine lost at least 5 percent of their body weight, according to the FDA. Those who dieted and exercised alone were less successful: Only 17 percent lost 5 percent or more of their body weight.

Liraglutide – This drug was first approved in 2010 for the treatment of Type 2 diabetes. It helps promote insulin production in the pancreas, which in turn controls blood sugar.

In December 2014, the agency expanded the use of liraglutide for the treatment of obesity. Sold as Saxenda, this version of the drug is a higher dose than that used to treat diabetes. Unlike the other FDA-approved drugs on this list, which are taken orally, Saxenda is taken as a once-a-day shot. [13 Easy Kitchen Fixes that Can Help You Lose Weight]

According to the FDA, 62 percent of people who took Saxenda in clinical trials lost 5 percent or more of their body weight, compared with 34 percent who took a placebo. This drug also has a black-box warning because rodent studies showed that it caused thyroid tumors. It's unknown whether liraglutide could have the same effect in humans, but people with a family history of certain cancers should not take the drug. Studies are ongoing to track the long-term safety of the drug in humans and in rats.

Many patients ask about weight-loss drugs, Jin said, which is what prompted her to write about the available options. Many people don't qualify to take them, either because they are not overweight enough, or because they have other health conditions or are taking other drugs that could make using these treatments unsafe.

Others aren't committed to the type of intensive lifestyle change that is required of people who want to use these drugs to help them lose weight, she said.

The ideal candidates, Jin said, are those who are already trying to lose weight: "People who are very motivated, who have really truly adopted those lifestyle changes, and just are not having success getting that weight off."

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Stephanie Pappas
Live Science Contributor

Stephanie Pappas is a contributing writer for Live Science, covering topics ranging from geoscience to archaeology to the human brain and behavior. She was previously a senior writer for Live Science but is now a freelancer based in Denver, Colorado, and regularly contributes to Scientific American and The Monitor, the monthly magazine of the American Psychological Association. Stephanie received a bachelor's degree in psychology from the University of South Carolina and a graduate certificate in science communication from the University of California, Santa Cruz.