Zepbound vs Wegovy: what's the difference between tirzepatide and semaglutide?

Zepbound and Wegovy often get talked about as if they were the same thing. They're both once-weekly shots, and they work in similar ways. But they're different medicines, with different labels. Here's what's different, straight from each one's prescribing information: Wegovy and Zepbound.

1.What's in each one?

• Wegovy contains semaglutide, the same medicine as Ozempic. Its label covers a weekly shot and a daily tablet. This article compares the shots.
• Zepbound contains tirzepatide, the same medicine as Mounjaro.
• Don't use them together. Each label says using it with any other GLP-1 receptor agonist is not recommended (section 1, Limitations of Use).

2.How do they work differently?

Think of a receptor as a lock on the outside of a cell, and a hormone as the key. When the right key fits, the cell gets a message. After you eat, your gut releases hormones that act as keys, including GLP-1 (Holst, 2007). GIP is another of these hormones your body makes; the Zepbound label calls them native GIP and GLP-1.

• Wegovy is one key for one lock. Its label says semaglutide selectively binds to and activates the GLP-1 receptor (section 12.1).
• Zepbound is one key that fits two locks. Its label calls tirzepatide a GIP receptor and GLP-1 receptor agonist, and says it is built on the GIP sequence (sections 11 and 12.1).
• Both locks sit in appetite areas of the brain. The Zepbound label says both GIP and GLP-1 receptors are found in brain areas involved in appetite regulation, and that the extra GIP effect on food intake comes from nonclinical studies (section 12.1).
• Both slow the stomach. For tirzepatide, the label says the delay is largest after the first dose and gets smaller over time (section 12.2).

3.What is each one approved for?

Both labels say the medicine is used along with a reduced-calorie diet and more physical activity (section 1).

4.How do the doses step up?

Both start low and go up slowly. Each label says the steps are there to reduce the risk of stomach side effects. These are general facts from the labels; your prescriber decides your dose and when it changes.

• Wegovy shot: 0.25 mg once a week for weeks 1 to 4, then 0.5 mg, 1 mg and 1.7 mg, each for 4 weeks. The usual maintenance dose is 1.7 mg or 2.4 mg, and the label lists 7.2 mg as the maximum for some adults (section 2.2).
• Zepbound: 2.5 mg once a week for 4 weeks, then 5 mg. It can go up in 2.5 mg steps after at least 4 weeks on a dose. Maintenance is 5, 10 or 15 mg (10 or 15 mg for sleep apnea), and the maximum is 15 mg (sections 2.1 and 2.2).
• The milligrams don't compare. They're different molecules, so a bigger number on one isn't “more” than the other.

5.How long does each one stay in your body?

Both carry a fatty side chain that lets them hold on to albumin, a protein in your blood. That slows how fast the body clears them, which is why one shot lasts a week. Semaglutide's is a C18 fatty acid; tirzepatide's is a C20 fatty acid that, in its label's words, prolongs the half-life.

• Wegovy: half-life about 1 week. It peaks 1 to 3 days after a shot and is in your blood for about 5 to 7 weeks after the last dose (section 12.3).
• Zepbound: half-life about 5 to 6 days. It peaks about 24 hours after a shot (range 8 to 72 hours) and reaches a steady level after 4 weeks of weekly doses (section 12.3).

6.Do they have the same side effects?

The most common ones are much the same: nausea, diarrhea, vomiting, constipation and stomach pain, mostly while the dose is stepping up. Both labels say rates from one medicine's trials cannot be directly compared with another's (section 6.1), so we don't put their percentages side by side.

One real label difference is birth control pills. Because tirzepatide slows the stomach, the Zepbound label says pills may work less well for a while. Birth control that isn't taken by mouth shouldn't be affected. This note isn't in the Wegovy label.

7.Has anyone compared them head to head?

Yes. The SURMOUNT-5 trial (New England Journal of Medicine, 2025) compared the highest tolerated doses of tirzepatide and semaglutide in 751 adults with obesity and without type 2 diabetes, for 72 weeks. It was open-label, meaning people knew which one they got. On average, weight changed more with tirzepatide. That's a group average: it doesn't say which one is right for any one person.

8.How do I choose?

That's a decision for you and your prescriber, based on your health, your other medicines, how you tolerate it and what your plan covers. Cost and coverage change often, so check with your plan. If you're switching from one to the other, your prescriber decides the starting dose and the timing.