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Everything to know about the side effects of weight-loss medications

Insomnia? Nausea? Blood pressure spikes? How serious and which drugs? Here’s what to look out for, and more importantly, what to do about it.
Published June 6, 2023

When people talk about prescription weight-management medications, they tend to talk about results: the weight you can lose and the health risks you can minimize. And while the end goal can be motivating, it’s not the only part of the journey.

Weight-management medications—like all medications—have the potential for side effects. Are they mild? Generally, but not always. Can you lower your risk or make them less severe? In some cases, yes. Let’s talk about it.

5 medications FDA-approved for weight loss (treating obesity)

But first…a review of the medications:

  • Liraglutide (Saxenda) and semaglutide (Wegovy) are GLP-1 agonists that trigger hormonal activity to keep blood sugar low, reduce cravings, and increase feelings of fullness.
  • The combination of bupropion and naltrexone (Contrave) is an opioid blocker with an antidepressant that can help reduce emotional eating.
  • The combination of phentermine and topiramate (Qsymia) is a metabolic stimulant with an anticonvulsant that helps dampen appetite.
  • Orlistat (Xenical, Alli) is a lipase inhibitor that blocks the absorption of fat in the gut.

Possible side effects of GLP-1 agonist weight-loss injections

Since most GLP-1 agonists such as Wegovy and Saxenda (and the soon-to-be-approved Mounjaro, which combines a GLP-1 agonist with something called a GIP) are taken via injection, a little irritation or discomfort wherever you inject is fairly common. Beyond that, though, side effects tend to be limited to the gastrointestinal system, where these medications work by changing gut hormones. “The most commonly reported side effect is nausea, which feels like motion sickness or morning sickness,” says Dr. Sarah Fishman, M.D., a professor of medicine, endocrinology, diabetes, and bone disease at Icahn School of Medicine at Mount Sinai in New York City. Also on the list? Constipation and diarrhea, as well as some abdominal discomfort and bloating. Research indicates these effects could result from slower stomach emptying.

However, “these side effects are often intermittent, mild, and short-lived,” she says. They usually happen when you first begin taking the drugs, a period when you are steadily increasing your dosage. As a result, “they usually resolve within a few days of the injection, and within a few weeks of longer term use,” says Fishman.

Clinical trials for GLP-1 agonists have found that nausea occurs in 15% to 30% of patients, diarrhea in 15%, and vomiting in 10% (usually as a result of the nausea). You can take medicine to help, such as a proton pump inhibitor (PPI) to reduce stomach acid production, anti-nausea medication, or a laxative. But again, these side effects don’t usually last long. “Often enough, if the side effect is bad enough to call me, by the time I send in a prescription for the PPI or anti-nausea pill and they get the medications from the pharmacy, the symptoms have usually resolved," says Fishman. Lifestyle habits can also help: If you’re not properly hydrated and eating nutrient-dense food, you might experience more nausea, says Dr. Peter Vash, M.D., an endocrinologist and obesity medicine specialist based in Los Angeles.

A far less common side effect—the risk is less than 2%—is gallstones, which are small, rock-like deposits of hardened digestive fluid. This is likely because GLP-1 agonists can delay the emptying of bile from the gallbladder. “If a person has more severe obesity and loses weight very, very quickly, there's a possibility that the rapid weight loss may cause them to have gallstones,” says Vash. Losing at a rate of more than 3.3 pounds a week is when you can start to see the gallstone risk go up, which can then contribute to pancreatitis, or inflammation of the pancreas that can lead to complications if left untreated. However, Vash says, “that's a very rare side effect.”

And if you’ve heard that GLP-1s can increase your risk of thyroid cancer, don’t be alarmed. “There is a theoretical increased risk of medullary thyroid cancers, but it’s not clear how likely this is to actually happen in people,” says Fishman, who along with Vash stresses that the link has only ever been studied in animals.

Additionally, studies in rats, rabbits, and monkeys demonstrated that animals treated with these medications had higher rates of miscarriage, were born smaller, and were more likely to have birth defects. Thus, the FDA recommends that these medications not be taken during pregnancy and if you are hoping to become pregnant, that the medications be discontinued at least two months prior to pregnancy.

These aren’t all of the potential side effects for GLP-1s—you can find those in the medication guides for Saxenda, Wegovy, and Mounjaro.

Possible side effects of naltrexone/bupropion HCL (Contrave)

Contrave pairs two medications, both of which act on the opioid pathway in the brain; it has bupropion, otherwise known as Wellbutrin (a type of antidepressant), alongside naltrexone, also known as Narcan, which is used to treat opioid and alcohol dependency.

“The idea behind Contrave is that it really helps with emotional eating by interfering with that reward center in your brain—sort of the way it works for addiction,” says Fishman. “You don't get that feeling of goodness from eating any more.” It also helps with impulse control, addressing both the urge to snack and the satisfaction you get from it.

The side effects for this drug tend to impact your mood—think anxiety, insomnia, and irritability—which makes sense, seeing as the medication’s action is focused in the brain. This is why Fishman says those with a history of anxiety and insomnia aren’t great candidates for naltrexone/bupropion, and that’s also why it carries a warning from the FDA that it may lead to suicidal thoughts and behaviors (though the risk is very small). It can also produce dizziness, headache, and nausea—with nausea impacting roughly 30% of people, and fewer than 20% reporting any of the other adverse events.

As scary as all that can sound, the side effects tend to be mild, and your doctor might recommend modifying your daily dose to take one pill instead of two. One thing to keep in mind is that for this medication, the side effects don’t fade. “They are unlikely to improve with prolonged use,” says Fishman. So if they don’t go away and your side effects are intense, talk to your doctor about alternative weight-loss medications.

This isn’t the full list of side effects for naltrexone/bupropion HCL—you can find that in the medication guide for Contrave.

Possible side effects of phentermine/topiramate ER (Qsymia) for weight loss

Qsymia is a stimulant medication that combines phentermine and topiramate: phentermine works as a weight-loss medication by impacting the hypothalamus to suppress appetite, while topiramate is an anti-seizure medication that helps with weight loss, possibly by also suppressing your appetite.

Qsymia’s side effects include an increase in blood pressure in about 20% of patients—making it not advised for those with hypertension—as well as headache, nausea, and brain fog, which happen less commonly. These side effects can persist for as long as you take the medication. If that’s the case, Fishman says you could talk to your healthcare provider about taking just the phentermine without the topiramate, which will help with the brain fog. Otherwise, staying hydrated and taking over-the-counter pain relievers may help with headaches.

More seriously, Qsymia can cause birth defects. “I find that for people who have the potential to start a family or to continue their family, it's a very high-risk medication,” says Fishman, Thus, the FDA recommends that if you are of child-bearing potential, that you use a highly effective method of birth control and talk to your doctor about weaning off the medication if you consider getting pregnant in the near future.

This isn’t the full list of side effects for phentermine/topiramate ER—look in the medication guide for Qsymia for that.

Possible side effects of orlistat (Xenical/Alli)

While orlistat—which works by inhibiting the enzymes that break down fat in the gut, preventing your body from absorbing it—debuted back in 1999 to a lot of fanfare, Fishman says it’s become less popular for two big reasons: “side effects and minimal benefits.” Those side effects are mostly gastrointestinal, and can include diarrhea and abdominal pain in up to 30% of patients. Plus, says Vash, when you go to the bathroom, “it causes an oily discharge.” (Yep—the fat that your body isn’t absorbing has to leave your body somehow.) And, he says, it results in an average 6% weight loss, which is much lower than other weight-loss medications. The primary way to address orlistat’s side effects is to simply limit your fat intake, which prevents the non-absorbed fat from throwing off your digestive system.

This isn’t the full list of side effects for orlistat. You can learn more by reading the medication guides for Xenical and Alli.

The bottom line

The potential for side effects from weight-loss medication isn’t something to brush off—obesity is a chronic condition and these medications are designed for long-term use, so you want to find a drug that doesn’t cause a major disruption to your quality of life. If you’re experiencing more severe side effects on a daily basis, it’s worth talking to your healthcare provider to explore your other options or see how you can adjust your dosage.

It’s also important to pair any medical weight-loss option (obesity treatment) with a balanced diet, quality sleep, stress reduction, and regular physical activity—since they can not only improve your long-term results, but also ease the severity of some side effects. “If these medications are used with a behavioral lifestyle program to change eating behaviors, that's where the real magic comes in,” says Vash. “That, in my mind, signals long-term, successful weight management.”