Tirzepatide vs Semaglutide: What the Labels and a Trial Say

Short answer: Semaglutide (the active ingredient in Wegovy® and Ozempic®) activates one receptor, the GLP-1 receptor. Tirzepatide (the active ingredient in Zepbound® and Mounjaro®) activates two, the GIP receptor and the GLP-1 receptor. The labels also differ on what each medicine is approved to treat. One company-funded trial compared the two head to head in adults with obesity. This page lays out the differences from the FDA labels and that trial. It does not rank the medicines, and your prescriber decides what fits you.

How do tirzepatide and semaglutide work?

The Wegovy, Ozempic, Zepbound and Mounjaro injections are all given under the skin once a week. The labels describe the mechanism like this:

• Semaglutide: Wegovy’s label says semaglutide “acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor.” It describes it as a GLP-1 analogue with 94% sequence homology to human GLP-1.
• Tirzepatide: Zepbound’s label says tirzepatide “is a GIP receptor and GLP-1 receptor agonist” that “selectively binds to and activates both the GIP and GLP-1 receptors.” It adds that nonclinical studies suggest the GIP part “may further contribute to the regulation of food intake.”

For a plain-language introduction to GLP-1 medicines in general, see What is a GLP-1?.

What is each medicine approved for?

Each medicine is sold under more than one brand name, and each brand has its own label. The indications below are quoted or summarized from the labels on DailyMed as of October 30, 2026.

Brand	Active ingredient	Indicated for (summary)
Wegovy	Semaglutide	Reduce excess body weight and maintain weight reduction in adults with obesity or overweight plus a weight-related condition, and in certain patients 12 and older with obesity; reduce major cardiovascular events in adults with established cardiovascular disease and obesity or overweight; treat noncirrhotic MASH with moderate to advanced liver fibrosis in adults
Ozempic	Semaglutide	Improve glycemic control in adults with type 2 diabetes; reduce cardiovascular events and kidney outcomes in certain adults with type 2 diabetes
Zepbound	Tirzepatide	Reduce excess body weight and maintain weight reduction in adults with obesity or overweight plus a weight-related condition; treat moderate to severe obstructive sleep apnea in adults with obesity
Mounjaro	Tirzepatide	Improve glycemic control in adults and pediatric patients 10 and older with type 2 diabetes; reduce major cardiovascular events in certain adults with type 2 diabetes

The weight labels (Wegovy, Zepbound) say the medicine is used “in combination with a reduced calorie diet and increased physical activity.” The other brand pairs are covered in Ozempic vs Wegovy and Mounjaro vs Zepbound.

How long do they stay in the body?

The labels give the half-life, the time it takes for the amount of the medicine in the body to fall by half. The Ozempic label says semaglutide has a half-life of approximately 1 week, so it “will be present in the circulation for about 5 weeks after the last dose.” The Zepbound label refers to “the half-life of tirzepatide of approximately 5 days.” These are label averages from studies, not a prediction for any one person.

Did a trial compare tirzepatide with semaglutide directly?

Yes. SURMOUNT-5, published in the New England Journal of Medicine in 2025, randomized 751 adults with obesity but without diabetes to tirzepatide or semaglutide. According to the PubMed abstract, the average change in body weight at week 72 was -20.2% with tirzepatide and -13.7% with semaglutide, and the authors concluded that tirzepatide was superior for weight and waist circumference in that trial.

Keep the context in mind:

• The trial was funded by Eli Lilly, which makes tirzepatide.
• It enrolled adults without diabetes. Results may differ in other groups.
• Averages do not say how any one person will respond, and weight is only one of several things people and prescribers weigh.

Are the side effects different?

Both labels list stomach and bowel effects such as nausea, diarrhea, vomiting and constipation as common, and both open with a boxed warning about thyroid C-cell tumors seen in rodents. The two labels report percentages from different trials with different designs, so they should not be compared line by line. The numbers are in GLP-1 side effects: a plain-language guide.

What should you ask your prescriber?

Questions people bring to appointments include:

• Which label fits my diagnosis, such as obesity, sleep apnea or type 2 diabetes?
• Does my history include anything the boxed warning or contraindications mention?
• What does my insurance cover, and which brand is on the plan’s list?
• What should I track between visits?

How can you keep your own record?

If you switch medicines or brands, a log of dates, injection areas and how you felt gives your prescriber a clear timeline. Weeko, a shot tracker coming to iPhone and Android, is being built around that kind of simple log. It is a logbook, not medical guidance.

When to call your doctor

Call your prescriber or get emergency care if you have severe or ongoing stomach pain, signs of an allergic reaction such as swelling of the face or throat or trouble breathing, a lump or swelling in your neck, or symptoms of dehydration. Ask your prescriber before changing, switching or stopping any medicine.