Tirzepatide vs. semaglutide for weight loss

Tirzepatide consistently outperforms semaglutide in head-to-head trials, producing 6%--7% more weight loss. But this edge in effectiveness is only one of the differences between the two drugs. Here's a closer look at tirzepatide vs. semaglutide for weight loss, in particular.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. 

• It’s the active ingredient in two brand-name medications: Zepbound and Mounjaro.

• Only Zepbound is approved by the US Food and Drug Administration (FDA) for weight loss and management. 

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. 

• It’s the active ingredient in two brand-name medications: Ozempic and Wegovy.

• Only Wegovy is FDA-approved for weight loss and management.

*Average list price before insurance, discounts, or savings programs 

Which one is better: semaglutide or tirzepatide?

If we’re just talking brass tacks (and only about the brand-name weight loss drugs)…

Tirzepatide may be better if:

• Your main priority is weight loss. In a recent head-to-head study, people taking tirzepatide lost an average of 20.2% of their body weight after 15 months of treatment, while those taking semaglutide lost 13.7%.

• You want to treat obstructive sleep apnea (OSA). Tirzepatide, as Zepbound, is FDA-approved to treat OSA in adults with obesity.

Semaglutide may be better if:

• You prefer a pill over an injection. Semaglutide is also available as a daily oral tablet that’s FDA-approved for weight loss (the Wegovy pill), though it’s slightly less effective than the injection. 

• You’re concerned about side effects. Compared to tirzepatide, semaglutide may have less intense and less frequent side effects in people with type 2 diabetes. However, side effects also depend on the dose (higher dose means higher risk of side effects). 

• You want to treat additional conditions. Semaglutide, as injectable Wegovy, is FDA-approved to treat fatty liver disease in certain adults with liver fibrosis and for cardiovascular risk reduction in adults with heart disease and obesity or overweight. 

That said, everyone is different. So, there’s no one-size-fits-all answer to whether semaglutide or tirzepatide is better.

Sure, one may be more effective at weight loss (tirzepatide), but that doesn’t make it inherently “better.” Plus, your healthcare provider is the best person to help you determine which medication makes the most sense for you. 

Before chatting with your provider, it’s a good idea to establish a strong understanding of semaglutide vs. tirzepatide. This way, you can have a more informed conversation and feel confident in the treatment decision. So, let’s dig into this comparison, shall we?

See if you qualify

• Drug class: Semaglutide is a glucagon-like peptide-one receptor agonist, or GLP-1. 

• Brand name(s) for weight loss: Wegovy is currently the only brand name version of semaglutide that is FDA-approved for weight loss and management.

• Mechanism of action: Semaglutide works by mimicking GLP-1, a hormone produced in the intestines that can help regulate blood sugar and appetite. 

• Form and frequency: Wegovy is available as a weekly subcutaneous (under-the-skin) injection that comes as a single-use, pre-filled pen. It’s also available as a daily oral tablet.

• Dose strengths: Wegovy injection comes in five dose strengths: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg. Wegovy pill comes in four dose strengths: 1.5 mg, 4 mg, 9 mg, and 25 mg.

• Cost: Wegovy has  a list price of $1,349.02. The Wegovy injection has a cash price of $199–$349 per month, depending on the dose. And the Wegovy pill has a cash price of $149–$299 per month, depending on the dose. 

How does semaglutide work?

Semaglutide works by mimicking GLP-1, a gut hormone produced by your body. Like natural GLP-1, semaglutide targets and binds to GLP-1 receptors throughout your gastrointestinal tract, pancreas, and brain. This results in: 

• Slowing down digestion

• Encouraging the release of insulin after eating 

• Lowering the amount of glucagon (sugar) that gets released after eating

• Sending satiety (fullness) signals to your brain 

Together, these effects help control blood sugar and promote weight loss.  

• Drug class: Tirzepatide is a dual GIP receptor and GLP-1 receptor agonist.

• Brand name for weight loss: Tirzepatide is approved for weight loss under the brand name Zepbound.  

• Mechanism of action: Tirzepatide mimics both GLP-1 and GIP, another gut hormone that can impact blood sugar and appetite. 

• Form and frequency: Zepbound comes as a single-dose pen or a single-use vial that you inject with a syringe. You inject Zepbound once weekly on the same day each week.  

• Dose strengths: Zepbound comes in six dose strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg. 

• Cost: ​​Zepbound pens cost $1,086.37 per month before insurance or other discounts and savings programs. You can also access Zepbound vials for $299–$449 per month, depending on the dose.  

How does tirzepatide work?

While semaglutide only targets and binds to GLP-1 receptors, tirzepatide is a dual agonist that acts on both GLP-1 and GIP receptors. Research suggests this dual action may be why tirzepatide can be more effective than semaglutide for weight loss and blood sugar control. 

Like semaglutide, tirzepatide helps you lose weight by lowering blood sugar, increasing feelings of fullness, and slowing down digestion. 

Compared to semaglutide, tirzepatide is more effective for both weight loss and blood sugar control. 

In a 2025 study of tirzepatide vs. semaglutide, people without type 2 diabetes who took:

• Tirzepatide experienced an average weight loss of 20.2% after 72 weeks (~16.5 months)

• Semaglutide experienced an average weight loss of 13.7%after 72 weeks (~16.5 months)

A 2024 cohort study of people with obesity or overweight outside of a clinical trial also compared tirzepatide vs. semaglutide. After 12 months of treatment, people who took:

• Tirzepatide lost an average of 15% of their body weight

• Semaglutide lost an average of 8% of their body weight 

While the potential weight loss outcomes with both drugs are promising, these medications aren’t a cure-all. They’re most effective when combined with healthy lifestyle changes, says Marlena Klein, DO, a board-certified internal medicine physician. 

These include following a reduced-calorie diet and doing about 150 minutes of moderate exercise each week. 

Tizepatide and semaglutide are also meant to be taken long-term. If you stop taking them or stop them too soon, your appetite and food cravings may return, and you may gain back some or all of the weight you lost. 

• A 2022 study on semaglutide found participants regained about two-thirds of the weight they’d lost a year after stopping the medication. 

• A 2023 study on tirzepatide found that participants who switched to a placebo after losing about 21% of their body weight in three years gained back about 14% over another year. Meanwhile, those who continued tirzepatide lost an additional 5.5%. 

“The success of each medication can vary,” Dr. Klein says. “It depends on how well the patient partners with the medication, maintains lifestyle changes, and prevents weight regain.” 

The cost of weight loss medications can vary widely depending on insurance coverage, eligibility for savings programs, and other discounts. 

The following table compares the costs of semaglutide vs. tirzepatide with and without insurance.

Many insurance plans do not cover weight loss medications, such as semaglutide and tirzepatide. Check with your insurance plan by calling them directly, referring to your plan’s drug formulary, or using Ro’s (free!) GLP-1 Insurance Coverage Checker. 

How to save money on tirzepatide for weight loss (Zepbound)

• Access single-use vials of Zepbound through Ro for $299–$449 per month, depending on the dose.

• The Zepbound Savings Card can lower the cost of Zepbound to just $25 for a one-month or three-month supply if you have insurance.

• Use Zepbound coupons from online drug discount sites. 

How to save money on semaglutide for weight loss (Wegovy)

• Opt for the Wegovy pill, which you can get through Ro starting at the cash price of $149 per month. 

• Access Wegovy injections through Ro for $199 per month for the first two months, followed by $349 per month thereafter when you pay with cash (Note: The promotional $199 price is available through March 31, 2026, and valid for 0.25 mg and 0.5 mg doses of the drug).

• If you have commercial insurance with coverage for Wegovy, you may be able to pay as little as $25 per month for Wegovy injections or the Wegovy pill with the Wegovy Savings Card. Limitations and eligibility restrictions apply, though.

• Use Wegovy coupons from online drug discount sites. 

See if you qualify

If you feel you’re not losing enough weight on one GLP-1 medication, or if you’ve reached a plateau, you may consider switching to tirzepatide, according to Dr. Klein. Or maybe the side effects of semaglutide are too much for you, and you want to see if you handle tirzepatide better. 

According to a 2024 study, people with type 2 diabetes who switched from semaglutide to tirzepatide lost even more weight over three months. 

You’ll likely start at a lower dose of tirzepatide and gradually increase it to minimize side effects. 

"However, I would avoid jumping ship too quickly to another medication or switching back and forth,” Dr. Klein adds.

Some common side effects of tirzepatide include:

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Abdominal pain

• Decreased appetite

• Dizziness

• Fatigue

• Indigestion/upset stomach

• Hair loss

• Injection site reactions (rash, itching)

Some common side effects of semaglutide may include:

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Constipation

• Headache

• Fatigue 

• Indigestion or heartburn

• Dizziness

• Bloating

The most commonly reported side effects of either medication are gastrointestinal (GI) in nature. But they tend to be mild and manageable and go away the longer you take the medication. (In other words, as your body gets used to the drug.) 

But Dr. Klein says that each person tolerates the medication differently, and neither medication is known to have worse side effects than the other. 

“I have patients who cannot tolerate Wegovy (semaglutide) but can tolerate Zepbound (tirzepatide), or, alternatively, they tolerate Wegovy but not Zepbound," she says.

Rare but serious side effects 

Both tirzepatide and semaglutide can cause more serious side effects, though these are rare. These include:

• Allergic reactions. Though rare, some people have reported severe allergic reactions (including anaphylaxis) with both tirzepatide and semaglutide.  

• Pancreatitis. Both medications may increase the risk for pancreatitis, or inflammation of the pancreas, though this may be more likely to occur in people with a history of pancreatitis or who have other risk factors.  

• Thyroid tumors. Both tirzepatide and semaglutide carry black box warnings about an increased risk of thyroid tumors, including a rare form of thyroid cancer (medullary thyroid carcinoma). 

• Gallbladder disease. GLP-1s may increase the risk of gallbladder inflammation or gallstones, potentially due to the slower digestion that occurs with these medications.

• Kidney problems. People with existing kidney issues may notice worsening symptoms while taking these medications. 

Who should not take tirzepatide or semaglutide?

Tirzepatide and semaglutide are generally safe, but they may not be suitable for everyone, including:

• People with a personal or family history of thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)

• People with a personal or family history of pancreatitis 

• People with known hypersensitivity to any component of the medication 

• People who are pregnant, breastfeeding, and planning to become pregnant

Always consult a healthcare provider before starting a new medication. They can evaluate your individual and family health history, goals, and other medications to help determine if treatment with tirzepatide or semaglutide is right for you. 

See if you qualify

Choosing the right medication is a personal decision you should make with the guidance of your healthcare provider. 

Here are some helpful questions to ask to help figure out whether semaglutide or tirzepatide is right for you:

• Am I a good candidate for weight loss medication?

• How do Zepbound and Wegovy compare in terms of effectiveness?

• Are there any factors that would make one medication a better choice than the other?

• What are the potential side effects, and how do I manage them?

• Are there any other serious side effects or risks I should know about?

• How long will I need to take the medication?

• How much weight can I expect to lose, and when will I start to see results?

• How much does each medication cost?

• Are GLP-1s covered by my insurance?

• Am I eligible for discounts or savings programs to help with out-of-pocket costs?

Tirzepatide and semaglutide can both be effective treatments for weight loss. Which treatment is better for you and your unique needs depends on factors like your health status, goals, and more.

• Tirzepatide and semaglutide are two distinct drugs that work in slightly different ways. Tirzepatide targets GLP-1 and GIP receptors, while semaglutide targets only GLP-1 receptors. 

• Research suggests that tirzepatide may lead to 6%–7% more weight loss than semaglutide. This may be due to its dual-action mechanism, and it has been observed in randomized trials as well as non-randomized studies. 

• Both medications can cost more than $1,000 per month, but the Wegovy pill tends to be the least expensive option when comparing the two drugs. Insurance, discounts, and savings programs may help offset out-of-pocket costs. 

• Common side effects of both drugs include nausea, diarrhea, and vomiting. Side effects tend to be mild and manageable, and may go away over time. 

• Neither drug is meant to work in isolation. For optimal results, treatment with tirzepatide or semaglutide should be paired with a balanced, healthy diet and regular exercise.