Tirzepatide and semaglutide, the ingredients in popular weight loss drugs, can both cause side effects—but which one is easier to tolerate? Experts explain why the answer isn't so simple

Why You Might Tolerate One Weight Loss Drug Better Than Another, According to Experts

• Tirzepatide and semaglutide, the ingredients in popular weight loss drugs, can both cause side effects, such as nausea, vomiting, and diarrhea.
• One is not safer than the other—tolerance to the medications largely depends on the patient.
• There are several ways to avoid and ease side effects, experts said, such as starting with a low dose and eating small meals.

Prescriptions for Ozempic, Mounjaro, and other glucagon-like peptide-1 (GLP-1) receptor agonist drugs have skyrocketed in recent years. But even though the medications are used for similar purposes, people often have vastly different reactions to them.

Gastrointestinal issues, specifically nausea, are common among people who take GLP-1 drugs. However, sometimes side effects from tirzepatide (the active ingredient in Zepbound and Mounjaro) or semaglutide (Wegovy and Ozempic) can force people off the medications or lead them to try a different drug altogether.

There isn’t much data on the subject, but a 2024 study from researchers at Truveta found that, over a five-year period, about 11% of GLP-1 drug users switched from one medication to another.

And recent celebrity cases have brought the issue further into the spotlight.

In a March video posted to her Instagram, comedian Amy Schumer talked about how she switched from semaglutide to tirzepatide and is now having better results.

“I tried Wegovy, and I was like, puking, I couldn’t handle it. I don’t know if they’ve changed the formula, whatever. Mounjaro’s been great,” she said. “I’m having a really good experience with it.”

Previously, on a January episode of Howard Stern’s SiriusXM show, Schumer shared that when she was on Ozempic three years ago, she was left “bedridden” and “vomiting.”

So why, in Schumer’s case, did semaglutide cause unmanageable side effects, while tirzepatide didn’t?

According to obesity experts, people can react differently to GLP-1s, and how your body responds might depend on the medication itself and various factors, including age, sex, and diet.

Here’s what to know about semaglutide and tirzepatide side effects, why the drugs don’t always trigger the same reactions, and how to minimize adverse effects while you’re on a GLP-1 medication.

Which Side Effects Do People Experience on Semaglutide and Tirzepatide?

Semaglutide and tirzepatide have a lot in common. Both are GLP-1 receptor agonist medications that act on GLP-1 receptors in the brain, pancreas, and gastrointestinal tract, which in turn control blood sugar levels, slow stomach emptying, and reduce hunger and food cravings.

Tirzepatide and semaglutide also share a number of side effects—nausea, acid reflux or indigestion, constipation, and complete loss of appetite (beyond the intended effect) are most common, Rekha Kumar, MD, an endocrinologist at Weill Cornell Medicine, told Health.

Beyond these, the labels for Zepbound, Mounjaro, Ozempic, and Wegovy all warn users about possible diarrhea, vomiting, and stomach pain.

But there are slight variations beyond these side effects, particularly for the weight loss versions of these medications.

While Wegovy or Zepbound users are both warned about possible fatigue, belching, and heartburn, Zepbound could also cause injection site reactions, allergic reactions, or hair loss, and Wegovy could cause headache, dizziness, bloating, low blood sugar, stomach flu, gas, and runny nose or sore throat.

In general, though, these side effects are fairly similar. And for both medications, symptoms tend to improve over time as people get used to them, added Jorge Moreno, MD, internal medicine and obesity medicine physician at Yale Medicine.

Additionally, Morgan Stewart, PharmD, clinical associate professor of pharmacy practice at the University of Texas at Austin, told Health that these side effects are often dose-dependent. That means, regardless of whether people are taking tirzepatide or semaglutide, side effects are “more likely to happen at higher doses,” she said.

Why Might Your Body React Differently to Various GLP-1s?

Though they’re similar, tirzepatide and semaglutide are formulated differently. While semaglutide is just a GLP-1 agonist, tirzepatide is a dual-action medication, which means it’s both a GLP-1 agonist and a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist.

GIP is a hormone primarily responsible for lowering blood sugar. So tirzepatide, which acts on both GLP-1 and GIP receptors, is able to further lower blood sugar, cause weight loss, and improve lipid levels. This could be why both Zepbound and Mounjaro have been shown to outperform Wegovy and Ozempic in terms of weight loss benefits, said Stewart.

It might also be a potential explanation for why some people tolerate the medications differently. In her practice, Stewart said she's noticed that “tirzepatide sometimes causes more side effects than semaglutide because it works on two hormones instead of one.”

But Kumar has seen the opposite. She said it’s often easier to space out tirzepatide doses and increase them more gradually over time, so she’s noticed tirzepatide is less likely to cause gastrointestinal issues among her patients as compared to semaglutide.

Moreno told Health that he’s treated many people who experienced intense side effects with semaglutide that significantly lessened when they switched to tirzepatide. However, “I’ve had the reverse occur as well, where people tolerate semaglutide better,” he explained.

For now, this kind of anecdotal evidence is all that’s out there—there’s little research putting tirzepatide and semaglutide’s side effects head-to-head on a wide scale.

It may be that tolerating tirzepatide or semaglutide simply comes down to each individual—people can have different tolerances to medication types and doses depending on their age, genetics, and sex, Kumar said.

Lifestyle may change things, too. Your activity levels, the medications you take, and your diet can affect your risk of experiencing GLP-1 side effects, said Kumar.

The same is true for your starting dose. “If the starting dose is too high or increased too quickly, side effects like nausea are more likely,” said Stewart.

So, if you’re having fewer side effects after switching from Ozempic to Mounjaro, for example, it could be because your body handles the formulation better. Or it could be because your physician started you on a lower dose, or you’re now eating well and exercising more consistently.

How to Minimize Semaglutide and Tirzepatide Side Effects

Regardless of which GLP-1 medication you’re taking, there are a few steps you can take to lessen your chance of developing side effects.

For one, start at a low dose and ramp up gradually over time, Stewart recommended.

Eating smaller meals and limiting consumption of fried foods, desserts, and high-fat meats such as steak can also be incredibly helpful for some people, added Moreno, as these foods can exacerbate negative gastrointestinal side effects.

Prescription or over-the-counter anti-nausea or constipation medications can also be a good way to alleviate some of these issues.

It’s important to stay hydrated, too—Kumar said people often forget to drink water when their appetite is suppressed. “I have seen such bad dehydration that people land in the [emergency room] with kidney failure,” she said.

If you continue to experience harsh or uncomfortable side effects day after day, it’s best to talk to your doctor—especially if GLP-1 side effects are interfering with your ability to function.

In these situations, Kumar said she usually advises patients to stop taking their GLP-1 to see if side effects go away. From there, she’ll ask for a detailed account of her patient’s diet to see if certain foods or beverages might have triggered the bad reaction. Depending on those answers, she’ll have the patient try a lower dose of the drug with a few behavioral changes, or she’ll switch their medication.

At the end of the day, every person—and body—is unique, said Moreno, and obesity physicians should tailor the treatment plan to each patient’s needs.

“Obesity treatment is not a one-size-fits-all approach,” he said.

Edited by Health, where she edits and publishes news articles on trending health and wellness topics. Her work has been featured in The Heights, an independent student newspaper at Boston College, and Minnesota Monthly." tabindex="0" data-inline-tooltip="true"> Julia Landwehr Julia Landwehr Julia is the associate news editor for Health, where she edits and publishes news articles on trending health and wellness topics. Her work has been featured in The Heights, an independent student newspaper at Boston College, and Minnesota Monthly. learn more Read more:

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This story originally appeared on: Health News - Author:Julia Ries