The WeightWatchers guide to weight-loss medications

When you think of weight-loss medication, you might automatically think of GLP-1s like Wegovy and Zepbound. And that makes sense, seeing as they’ve been making headlines for their weight-loss benefits (in addition to other health perks) for years now. But they’re far from the only weight-loss medications being prescribed these days. They’re part of a whole lineup of drugs that can help you lose weight, including some that have been around for decades (or in one case, since 1959!). Here, experts break down the differences between all of the FDA-approved options.

How do weight-loss medications work?

It depends on the exact medication, but weight-loss medications typically work by suppressing your appetite, increasing feelings of fullness, or both. Newer ones, like GLP-1s, as well as older medications, like phentermine-topiramate and bupropion-naltrexone, target areas of the brain associated with appetite so you don’t feel as hungry. “The brain is the final common pathway for any drug that reduces appetite,” says Dr. Robert Kushner, M.D., a professor of medicine in endocrinology and medical education at Northwestern University Feinberg School of Medicine in Chicago.

Types of weight-loss drugs

While most weight-loss drugs require a prescription, there is one you can get over-the-counter.

Over-the-counter (OTC) weight-loss medications

There’s only one over-the-counter medication for weight loss that’s been approved by the FDA, and that’s Alli, a brand name of the drug orlistat. (Xenical, which has a higher amount of orlistat than Alli, is available by prescription.) Orlistat works by preventing your body from absorbing some of the fat in your diet so that it instead gets removed in your waste.

If you’ve seen other weight-loss products on the shelf at stores, they may be a waste of money at best — and at worst, dangerous to your health. ”Everything else you may be thinking about is a dietary supplement with a completely different regulation,” says Kushner. They don’t undergo the rigor of safety and efficacy testing as required by the FDA and there’s no evidence that they work.

Prescription weight-loss medications

All other weight-loss medications, including injectable GLP-1s as well as oral medications like phentermine-topiramate (known by the brand name Qsymia) and bupropion-naltrexone (known by the brand name Contrave), are only available with a prescription from a licensed provider.

They all have FDA approval, which means that the medication has gone through extensive clinical trials to assess its efficacy and safety. In other words, “the drugs have to demonstrate a certain amount of weight loss,” says Kushner.

Common weight-loss medications

Here’s a deeper look at all the FDA-approved options currently available, including how they work and how much weight you can expect to lose.

Semaglutide (Wegovy, Ozempic, and Rybelsus)

Semaglutide is in a category of prescription drugs called glucagon-like peptide-1 agonists, or GLP-1s, and they have upended the way obesity is treated. “The closest thing to magic today is a GLP-1,” says Dr. Peter Vash, M.D., an endocrinologist and internist in Los Angeles who specializes in obesity medicine. “They're safe and they're effective.” GLP-1s work by mimicking a naturally occurring hormone that increases insulin, thus lowering blood shower, and slows stomach emptying, which can help you feel fuller. It also targets certain appetite receptors in your brain, bringing down hunger more.

There are different drugs within the GLP-1 category, but semaglutide, which is a weekly injectable medication, is among the best known due to its large impact on weight and the fact that it was the first GLP-1 approved for weight loss. One study found that semaglutide can lead to an average 15% weight loss in a little over a year. It’s prescribed under the brand name Wegovy for weight loss and Ozempic and Rybelsus for treatment of type 2 diabetes (Rybelsus is an oral version as opposed to an injectable).

Tirzepatide (Zepbound, Mounjaro)

Tirzepatide works similarly to semaglutide, but in addition to mimicking GLP-1, tirzepatide also mimics the hormone GIP (which stands for glucose-dependent insulinotropic polypeptide). GIP is another gut hormone that helps your body release insulin to control blood sugar and slows digestion, thereby making you feel less hungry. Zepbound is the brand name of tirzepatide approved for weight loss, while Mounjaro is FDA-approved for treatment of type 2 diabetes. Both are given via weekly injections.

Thanks to the dual action of GIP and GLP-1, tirzepatide has been found to have a bigger impact on your weight than other prescription GLP-1s. In a study published in the New England Journal of Medicine, people lost 20.9% of their starting weight after roughly a year on tirzepatide. But “although tirzepatide kind of outpaces semaglutide in head-to-head trials, both of them are very effective,” says Kushner.

Liraglutide (Saxenda, Victoza)

Liraglutide, which comes as a daily injection, was the first prescription GLP-1 FDA-approved for weight loss. But it’s been overshadowed in recent years by semaglutide and tirzepatide. This is because it doesn’t have the same impact on weight as the newer GLP-1s and is given daily. “Although it is approved for obesity treatment, it's not a preferred drug because it's less effective and needs to be taken daily,” Kushner says.

When people paired liraglutide with diet and exercise, liraglutide leads to an average weight loss of 5% to 10% in about a year. Similar to the other GLP-1s, there is a version approved for weight loss (Saxenda) and one for treatment of type 2 diabetes (Victoza).

Phentermine-topiramate (Qsymia)

Rather than mimicking hormones to turn off the brain’s hunger cues — as GLP-1s do — prescription phentermine-topiramate “regulates what we call neurotransmitters, or signals directly in the brain, to alter appetite,” says Kushner. It combines phentermine, a stimulant that reduces your appetite, and topiramate, an anti-seizure medication that helps lower your appetite and make you feel fuller longer.

An oral medication, which comes as a pill that you take once a day, phentermine-topiramate is an appetite suppressant that cuts desire for food. “It also stimulates you a little bit, and you get a bit of a bounce emotionally,” says Vash. In one study, 75% of people taking phentermine-topiramate lost at least 5% of their body weight after a year.

Bupropion-naltrexone (Contrave)

Like phentermine-topiramate, bupropion-naltrexone is a daily pill that targets neurotransmitters in the brain. Bupropion is an antidepressant that reduces appetite, while naltrexone helps control cravings (it’s prescribed alone to treat certain addictions). Together, the combo reduces your appetite and your focus on food, so you don’t feel as hungry. Contrave is a brand name pill that contains both drugs, but you can also take them as two separate, generic pills.

Research has found that after 56 weeks, roughly 50% of people taking Contrave lost more than 5% of their body weight.

Orlistat (Xenical, Alli)

Orlistat comes in two versions: Alli, which is sold over-the-counter for weight loss, and Xenical, which is a stronger version available with a prescription. They both come as a capsule that you take three times a day (usually with your meals). It works by “blocking about 30% of fat from being absorbed in the body,” says Kushner.

The studies are mixed on how much weight you can lose. One study found that even in combination with diet, exercise, and lifestyle changes, 120 mg of orlistat (the dose found in prescription-only Xenical) can better help with minimizing weight gain versus losing weight. (In fact, at the end of the trial, people had actually slightly increased their weight.) But another study found that people taking that same dosage experienced more than 10% weight loss after a year when pairing it with a low-calorie diet.

Setmelanotide (Imcivree)

Setmelanotide is a prescription daily injection that targets one of the brain’s hunger pathways involved in certain genetic causes of obesity; in doing so, it helps reduce appetite, increase fullness, and boost calorie burn. Because of the way it works, it's only FDA-approved for people with certain genetic conditions, namely: Proopiomelanocortin (POMC) deficiency, Proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency, Leptin receptor (LEPR) deficiency, and Bardet-Biedl syndrome (BBS). These conditions can cause weight gain because of hyperphagia, which is a feeling of extreme or insatiable hunger. Unless you have one of these conditions, you probably wouldn’t need or medically qualify for this particular weight-loss drug.

Benefits of weight-loss medications

Weight loss itself might be your focus, but the real benefits come from what it does to your overall health, like reducing risk factors for many chronic diseases. “Weight loss tends to improve things like blood sugar, cholesterol, and blood pressure,” says Kushner. A recent study found that even “low-level” weight loss (defined as losing less than 5% of your body weight) can improve heart, kidney, and liver health, as well as lower inflammation and boost quality of life.

But some weight-loss medications have added benefits, like GLP-1s. “Those drugs, independent of weight loss, may reduce the risk of having a second heart attack and are now being looked at for Alzheimer's,” says Kushner. “They're even being studied for [treating] substance abuse disorder.”

Who qualifies for weight-loss drugs?

When approving a medication, the FDA determines what it can be used for and also who qualifies for them. For weight-loss medications, the qualifications tend to be based on body mass index, or BMI. “Anyone with a body mass index of 30 or more, which is defined as obesity, qualifies for consideration of these medications,” says Kushner. That threshold drops to a BMI of 27, which is in the middle of the overweight category, for people who have a weight-related medical condition like type 2 diabetes, hypertension, or cholesterol. Those with a BMI more than 25, which is considered overweight, can also be evaluated by their doctor to determine if they are candidates for these medications.

Beyond that, doctors consider other things when determining who is a good candidate for these drugs. For instance, when considering if a patient should take a weight-loss medication, Kushner likes to factor in how willing patients are to make lifestyle changes (like improving their diet and exercise routines), what their overall goals are, and if they have any medical conditions that would improve with weight loss.

How much do weight-loss medications cost?

Weight-loss medications come with a huge range of price tags, and how much you pay ultimately depends on factors like which drug you’re taking and your insurance plan. GLP-1s tend to be the most expensive of the bunch, costing more than $1,000 if you’re paying out of pocket, and many insurance plans don’t cover them. Phentermine-topiramate and bupropion-naltroxene are less expensive, costing $100 to $200 for a 30-day supply without insurance (although they may be cheaper if your provider prescribes a generic version of these drugs). Xenical, meanwhile, can cost several hundred dollars for a 60-day supply without insurance, while Alli can be found for around $70 at most drugstores.

Side effects of weight-loss medications

The side effects vary from medication to medication, and they largely depend on the type of weight-loss drug in question. “All the GLP-1 medications share the same side-effect profile, which is mostly gastrointestinal,” says Kushner. Their common side effects include nausea, diarrhea, and constipation, although they tend to be mild to moderate when you use them properly and improve as your body gets used to the medication.

As for other medications that work directly in the brain, like phentermine-topiramate and bupropion-naltrexone, their side effects are a bit different. “Some of them can vary, but you get dry mouth, dizziness, and headache,” says Kushner. “But they tend to be mild.” Orlistat has some unique (and unpleasant) side effects, like gas, oily or loose stools, and oily spotting (since your body has to get rid of the excess fat that it's not absorbing).

For a full list of side effects for these medications, visit the manufacturer’s website or look at the packaging insert.

Are weight-loss drugs a substitute for exercise?

And we say this with our full chest: No. Weight-loss medications “are not a substitute for good dietary habits and physical activity,” says Vash. “They should be used alongside them, not as a substitute for them.” In fact, the research on weight loss for these drugs combines them with a healthier diet and increased exercise.

That’s just because of the nature of weight-loss medications, which largely work by reducing appetite. “That means that if you respond to the medication, you're going to eat less food, and therefore you're going to lose weight because you're eating fewer calories,” says Kushner. “But that does nothing for your fitness level, your muscle health, your stamina, and your strength, balance, and agility.”

Losing weight also causes you to lose muscle alongside fat — something strength training can help you with. On top of that, exercise on its own can improve cardiovascular and bone health, “so it’s never an either-or decision,” Kushner says. “It's always medication and remaining physically active and eating a healthy, balanced diet.”

That’s why WeightWatchers Clinic doesn’t just provide access to medication, but also tailored nutrition and exercise programs and one-on-one appointments with clinicians and dietitians.

Upcoming weight-loss medications

As many options as there are right now, there will likely be more in the future thanks to the promising weight-loss medications on the horizon, according to Kushner. “There are dozens of medications that are in studies that will likely be approved over the coming years,” he says. These may include ones that combine other components with GLP-1, like tirzepatide does, or ones that work to mimic other gut hormones with different qualities.

The available format of existing medications may also change. “The most exciting area is the availability of oral medications and those are likely coming around the next year or two,” says Kushner. “So you'll be able to come close to reproducing what we get with a weekly injection with an oral daily medication.”

The bottom line

If you’re considering a weight-loss medication, there are more options out there than ever before. GLP-1s, which you inject once a week or daily, are the most effective drugs, while oral medications are more convenient and tend to cost a lot less. In general, the FDA-approved medications have mild side effects that tend to get better with time. To see the biggest health improvements, combine any weight-loss medication with regular exercise and a healthy diet. Ultimately, your provider at WeightWatchers Clinic can help determine the right weight-loss medication for you.