Do prescription weight-loss pills work?

The term weight-loss pills is sort of a misnomer. For one, it’s usually used to describe a class of prescription drugs that do far more than promote weight loss. Also? Many aren’t even pills. In reality, these prescription medications are treatments that can help manage a chronic condition, obesity, that affects over 40% of Americans, according to data from the Centers for Disease Control and Prevention (CDC).

“Think about the way we treat any other medical condition, like high blood pressure, diabetes, or heart disease,” says Dr. Amanda Velazquez, M.D., director of obesity medicine at The Center for Weight Management and Metabolic Health Cedars-Sinai in Los Angeles. “Similarly, this is how we treat obesity: healthy lifestyle and often medication.”

How does prescription weight-loss medication work?

In general, prescription weight-loss drugs, known as anti-obesity medications, target different hormones or processes in the body that can do one or more of the following:

• Reduce appetite: Some meds do this by altering hunger hormones like insulin, ghrelin, and leptin, making it difficult for the brain to send signals to the rest of the body that say “I want food.”
• Increase feelings of fullness: Anti-obesity drugs may also mimic natural hormones, like glucagon-like peptide 1 (GLP-1), that slow stomach emptying and tell the brain you're full.
• Minimize cravings: Some medications help regulate dopamine, the hormone and neurotransmitter behind the brain’s reward system; this can quiet food cravings.

What we talk about when we talk about hunger

Prescription weight-loss medications work by controlling hunger—or at least that’s the generally accepted explanation. But what if…you’re not all that hungry to begin with? “We know that these medications affect appetite and gastric emptying,” says Michelle Cardel, Ph.D., R.D., senior director of clinical research and nutrition at WeightWatchers®. “What we don’t know is if—and what—other mechanisms are at play that could be driving weight loss as well.” (It’s not as if the research was only done on people who said they had trouble quelling their appetite.) Ultimately, it’s up to you and your healthcare provider to decide if any of these drugs make sense for your treatment plan.

Are prescription weight-loss pills safe?

Unlike over-the-counter diet supplements and pills, which are unregulated by the FDA and can have some very serious health consequences like liver damage or heart trouble, “FDA-approved prescription weight-loss medications have gone through rigorous research processes to assess both the safety and effectiveness of the medications,” says Velazquez.

That said, even if an anti-obesity medication has been tested in clinical trials and approved by the FDA, it can still come with certain side effects and risks—GI issues, for example. Your healthcare provider should review these with you during your consultation, says Dr. Diana M. Plata, M.D., an obesity and sleep medicine physician for Northwest Community Healthcare in Arlington Heights, Illinois.

How do you know which prescription weight-loss medication is right for you?

Everybody—and legit every body—is unique. To determine the best treatment plan for you, your healthcare provider will start with an extensive conversation. They’ll consider your medical history and your family medical history, plus:

• Body mass index (BMI): Weight-loss medications are FDA-approved for people with a BMI of 30 or more, and for people with a BMI of 27 or higher plus a qualifying medical condition, such as diabetes.
  
  
• Drug factors: Before a medication is prescribed, your provider will consider and discuss its cautions, like whether it will have any kind of effect on uncontrolled hypertension or a seizure disorder. Other cautions—like whether you’re a smoker or regularly have migraines—will also sway the provider’s prescription recommendation. On the flip side, some obesity medications have a dual benefit (i.e. maybe they improve cholesterol or blood sugar levels, or help prevent migraines) that is also taken into consideration.
  
  
• Your preferences: Anti-obesity medications are available in pill and injection form, and dosing frequency can vary from weekly to multiple times a day. If you qualify for the medication, you may want to consider which delivery method and cadence is most comfortable for you before getting your prescription. Another very (very) important personal preference to consider: whether or not a medication is covered by insurance. If it’s not, your provider might have leads for samples and coupons, though these are short-term fixes for a long-term treatment.

6 FDA-approved weight-loss medications for long-term obesity treatment

1. Contrave (naltrexone HCl/bupropion HCl)

FDA-approved for obesity in 2014, Contrave is a combination of two generic drugs: bupropion, an antidepressant, and naltrexone, which is used for drug addiction. It works by decreasing appetite and cravings.

What the science says:
In a clinical trial of more than 1,700 men and women, which was sponsored by the drug’s manufacturer, those taking Contrave lost 5.4% of their body weight on average over the 56 weeks they were tracked.

Possible side effects:

• Nausea and vomiting
• Headache
• Constipation
• Dizziness
• Insomnia
• Seizures
• Diarrhea
• Increased blood pressure and heart rate
• Increased risk of suicidal thoughts

You can find a complete list of side effects on the Contrave site.

2. Qsymia (phentermine and topiramate extended-release)

Qsymia, approved in 2012, is a combination of two medications: phentermine, which reduces appetite, and topiramate, which is used to treat seizures and migraines. It helps curb hunger and make people feel full sooner, which often results in eating less.

What the science says:
Two large trials conducted in 2012 found that, after one year of treatment, people on Qsymia lost significantly more weight than participants who took a placebo. Nearly all of the patients in the trial lost at least 5% of their body weight, and about half of the trial participants lost 10% of their weight.

Possible side effects:

• Constipation
• Dizziness
• Dry mouth
• Tingling of the hands and feet
• Trouble sleeping and excessive tiredness

You can find a complete list of side effects on the Qsymia site.

3. Saxenda (liraglutide)

Saxenda is an injection that’s self-administered once daily, originally approved to treat type 2 diabetes (Victoza) and approved at a higher dose to treat obesity in 2014. It works by mimicking the hormone GLP-1, which helps regulate satiety, the feeling of fullness.

What the science says:
Over the course of 56 weeks, about 63% of those on liraglutide lost at least 5% of their body weight (compared with 27% of those on a placebo), according to research in The New England Journal of Medicine. Thirty-three percent of patients on liraglutide lost more than 10% of their body weight.

Possible side effects:

• Nausea
• Diarrhea
• Constipation
• Headache
• Vomiting
• Low blood sugar
• Upset stomach or stomach pain
• Fatigue
• Dizziness

You can find a complete list of side effects on the Saxenda site.

4. Wegovy (semaglutide)

First approved under the brand name Ozempic in 2017 for the treatment of type 2 diabetes, this higher dose of semaglutide was approved in 2021 under the brand name Wegovy for obesity. A once-weekly, self-administered injection, Wegovy is a GLP-1 agonist that works by quieting hunger signals and promoting feelings of fullness.

What the science says:
In a 68-week clinical trial, participants who took semaglutide lost nearly 15% of their body weight, while their peers who took a placebo lost about 2.5%, according to a study published in The New England Journal of Medicine. The semaglutide group also showed improvements in blood pressure, cholesterol, and blood sugar.

Possible side effects:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Abdominal pain
• Headache
• Fatigue
• Dizziness
• Indigestion
• Gas
• Acid reflux

You can find a full list of side effects on the Wegovy site.

5. Zepbound (tirzepatide)

While the version of tirzepatide known as Mounjaro has been available for treating type 2 diabetes since 2022, a version sold under the name Zepbound, atirzepatide, was approved for obesity in 2023. It's also a once-weekly, self-administered injection and it combines a GLP-1 agonist with a GIP agonist, which together decrease hunger and increase fullness.

What the science says:
A 2022 study in the New England Journal of Medicine found that people taking 15mg of tirzepatide weekly for 15 months lost an average of 20% of their bodyweight. They also improved blood sugar, blood pressure, cholesterol, and triglyceride levels.

Possible side effects:

• Nausea
• Diarrhea
• Constipation
• Vomiting
• Indigestion
• Stomach Pain

You can find a full list of side effects on the Zepbound site.

6. Xenical and Alli (orlistat)

Approved in 1999 as a prescription capsule (Xenical) and as a lower dose, over-the-counter capsule in 2007 (Alli), orlistat is taken three times daily with meals and decreases the amount of dietary fat absorbed by the intestines. As a result, the remaining fat is eliminated from the body during bowel movements.

What the science says:
In a six-month study published in the Journal of Obesity, participants who took Xenical lost, on average, over 9 pounds. And another study found that, compared to placebo, orlistat led to a significant reduction in weight along with waist circumference, total cholesterol, and LDL (“bad” cholesterol) levels.

Possible side effects:

• Oily spotting on underwear after passing gas
• Loose or oily stools
• Diarrhea
• Difficulty controlling bowel movements or the urgent need to go
• Abdominal pain
• Irregular menstrual cycles
• Headaches
• Anxiety
• Hives, itching, or rash
• Trouble breathing or swallowing
• Fatigue or weakness
• Loss of appetite
• Nausea or vomiting

You can find a complete list of side effects on the Xenical and Alli sites.

The bottom line

For people living with obesity and other qualifying conditions, prescription anti-obesity medications can be a safe and effective part of the treatment plan. For long-term weight management, however, they’re best paired with a lifestyle program, like WeightWatchers, to build a foundation of healthy habits—including nutrition, activity, and sleep. Determining whether they’re right for you, however, always starts with an in-depth convo with your healthcare provider.