Key takeaways
Semaglutide (Ozempic, Wegovy, Rybelsus) activates one gut-hormone receptor, GLP-1 (glucagon-like peptide-1). Tirzepatide (Mounjaro, Zepbound) activates two, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1, and in the SURMOUNT-5 head-to-head trial it produced more average weight loss at 72 weeks: 20.2% versus 13.7%. Both come as once-weekly injections with the same boxed warning about thyroid C-cell tumors.
- 01Different targets. Semaglutide is a GLP-1 receptor agonist; tirzepatide is a dual GIP and GLP-1 receptor agonist.
- 02Both are weekly. Half-lives are about 1 week for semaglutide and about 5 days for tirzepatide.
- 03The mg numbers do not compare. Wegovy steps from 0.25 to 2.4 mg; Zepbound steps from 2.5 to 15 mg.
- 04SURMOUNT-5 favored tirzepatide on weight in a trial funded by its maker, Eli Lilly.
- 05Compounded copies are not FDA-approved, and the FDA has declared both shortages resolved.
This article belongs to our GLP-1 Peptides category, which covers the wider topic.
This comparison sticks to the FDA prescribing information and published head-to-head trials. It is educational, not medical advice, and it does not suggest a dose or a drug for anyone.
How do semaglutide and tirzepatide work?
Both copy gut hormones released after meals. They differ in how many receptors they switch on.
GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are gut hormones that help release insulin when blood sugar rises. A receptor agonist binds to a receptor and turns it on. Both drugs are peptides, short chains of amino acids (see what peptides are).
The Ozempic prescribing information describes semaglutide as a GLP-1 analogue with 94% sequence homology to human GLP-1. The Zepbound prescribing information says tirzepatide activates both the GIP and GLP-1 receptors, in one molecule.
Why both are once weekly
Half-life is the time it takes for the drug level in your blood to fall by half. For semaglutide it is about 1 week. For tirzepatide it is about 5 days, or 5 to 6 days in people with obesity. Both last long enough for one injection a week.
Free calculator
Retatrutide Calculator. Retatrutide adds a third target, the glucagon receptor, and is still investigational (not FDA-approved); the retatrutide calculator covers its unit math.
Which brands contain each drug, and what are they approved for?
Approved uses belong to each brand, not to the molecule.
| Brand | Drug and form | FDA-approved uses |
|---|---|---|
| Ozempic injection | Semaglutide, weekly | Type 2 diabetes; lower heart and kidney risks in adults with type 2 diabetes and heart or kidney disease |
| Rybelsus, Ozempic tablets | Semaglutide, daily | Type 2 diabetes; lower risk of major heart events in high-risk adults |
| Wegovy injection | Semaglutide, weekly | Weight reduction in adults and children 12 and older; lower heart risk in adults with heart disease and excess weight; MASH with moderate to advanced fibrosis |
| Wegovy tablets | Semaglutide, daily | Weight reduction in adults; lower heart risk in adults with heart disease and excess weight |
| Mounjaro | Tirzepatide, weekly | Type 2 diabetes in adults and children 10 and older; lower risk of major heart events in high-risk adults |
| Zepbound | Tirzepatide, weekly | Weight reduction in adults; moderate to severe obstructive sleep apnea in adults with obesity |
From the US labels: Ozempic injection (5/2026), Rybelsus and Ozempic tablets (1/2026), Wegovy (6/2026), Mounjaro and Zepbound (8/2026).
MASH (metabolic dysfunction-associated steatohepatitis) is fatty liver disease with inflammation. Obstructive sleep apnea is when the airway keeps closing during sleep. The Wegovy prescribing information covers the injection and tablets; the Mounjaro prescribing information covers type 2 diabetes only.
Semaglutide vs tirzepatide at a glance
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Receptors activated | GLP-1 | GIP and GLP-1 |
| Brands | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound |
| Injection frequency | Once weekly | Once weekly |
| Elimination half-life | About 1 week | About 5 days |
| Label starting dose, injection | 0.25 mg weekly for 4 weeks | 2.5 mg weekly for 4 weeks |
| Label maximum, injection | 2 mg (Ozempic); 7.2 mg (Wegovy HD) | 15 mg (adults) |
| Weight maintenance (Wegovy, Zepbound) | 1.7 or 2.4 mg; up to 7.2 mg | 5, 10 or 15 mg |
| SURMOUNT-5 weight loss, 72 weeks | 13.7% | 20.2% |
| Boxed warning | Thyroid C-cell tumors in rodents | Thyroid C-cell tumors in rats |
Label doses show scale and are not dosing advice. Trial figures are mean weight changes.
What do the FDA labels say about titration?
Titration means starting low and stepping up in stages to limit stomach side effects. Both labels step up no faster than every 4 weeks.
The Wegovy label starts at 0.25 mg once weekly and steps up every 4 weeks to a week-17 maintenance dose of 2.4 mg (recommended) or 1.7 mg for adult weight reduction. Adults who have tolerated 2.4 mg for at least 4 weeks and need more weight reduction may go up to 7.2 mg (Wegovy HD).
The Zepbound label starts at 2.5 mg once weekly for 4 weeks, a dose meant only to start treatment. It then rises in 2.5 mg steps after at least 4 weeks on each dose, to a 15 mg maximum. Maintenance doses are 5, 10 or 15 mg for weight and 10 or 15 mg for sleep apnea.
Ozempic starts like Wegovy and Mounjaro like Zepbound, with adult label maximums of 2 mg and 15 mg.
| Weeks | Wegovy injection | Zepbound |
|---|---|---|
| 1 to 4 | 0.25 mg | 2.5 mg |
| 5 to 8 | 0.5 mg | 5 mg |
| 9 to 12 | 1 mg | 7.5 mg |
| 13 to 16 | 1.7 mg | 10 mg |
| 17 to 20 | 2.4 mg or 1.7 mg (maintenance) | 12.5 mg |
| 21 onward | Same maintenance dose | 15 mg (maximum) |
The fastest pace each label allows, shown to compare scale. Prescribers may hold a step longer or stop at a lower maintenance dose. This is not a schedule for any person.
What did head-to-head trials find?
Two large randomized trials compared the drugs directly. Both were open-label (participants knew their drug) and funded by Eli Lilly, which makes tirzepatide.
SURMOUNT-5: obesity without diabetes
SURMOUNT-5, published in the New England Journal of Medicine in 2025, randomized 751 adults with obesity and without type 2 diabetes to the maximum tolerated weekly dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks.
- Weight: average loss of 20.2% of body weight with tirzepatide and 13.7% with semaglutide.
- Waist: 18.4 cm smaller on average with tirzepatide and 13.0 cm with semaglutide.
- Side effects: mostly gastrointestinal and mild to moderate in both groups, mainly during dose escalation.
SURPASS-2: type 2 diabetes
SURPASS-2, published in the New England Journal of Medicine in 2021, compared tirzepatide 5, 10 and 15 mg with semaglutide 1 mg in 1,879 adults with type 2 diabetes for 40 weeks. HbA1c, a measure of average blood sugar over recent months, fell 2.01 to 2.30 percentage points with tirzepatide and 1.86 with semaglutide. Weight loss was 1.9 to 5.5 kg greater with tirzepatide.
How to read these results
- They are group averages. They do not predict what one person will experience; your prescriber can put them in context.
- SURPASS-2 did not test top semaglutide doses. It used 1 mg, below the current 2 mg Ozempic maximum.
How do the side effects and warnings compare?
Both labels list gut effects first and carry the same boxed warning.
- Semaglutide: the Ozempic label lists nausea, vomiting, diarrhea, abdominal pain and constipation. Wegovy adds headache, fatigue, dizziness and hair loss, among others.
- Tirzepatide: the Mounjaro label lists nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion and abdominal pain. Zepbound adds injection site reactions, fatigue, hair loss and reflux, among others.
Boxed warning: risk of thyroid C-cell tumors
A boxed warning is the FDA's strongest label warning. Both drugs caused thyroid C-cell tumors in rodents; whether they do in people is unknown. The labels say not to use either drug with a personal or family history of medullary thyroid carcinoma (MTC) or with multiple endocrine neoplasia syndrome type 2 (MEN 2). Report a neck lump, trouble swallowing, shortness of breath or lasting hoarseness to your prescriber.
Precautions the Wegovy and Zepbound labels share
- Acute pancreatitis and acute gallbladder disease
- Acute kidney injury from fluid loss after vomiting or diarrhea
- Severe gastrointestinal and allergic reactions
- Low blood sugar, mainly with insulin or drugs that raise insulin
- Diabetic retinopathy complications in type 2 diabetes
- Pulmonary aspiration (inhaling stomach contents) under anesthesia or deep sedation
How does the math differ between pens and vials?
A pen delivers a set dose in mg. A vial makes you measure a volume, so the math depends on the concentration.
Branded pens are labeled by the dose they deliver, so there is nothing to convert. Zepbound vials hold a fixed volume instead: 0.5 mL in a single-dose vial, or four 0.6 mL doses in a multi-dose vial. Each strength has its own concentration: a 2.5 mg single-dose vial is 5 mg/mL and a 15 mg one is 30 mg/mL.
Compounded vials have no standard strength; it depends on the pharmacy, or on how much water went into a powder. On a U-100 insulin syringe, 1 unit is 0.01 mL, so units measure volume, not drug (see how to read an insulin syringe).
Arithmetic only: at 5 mg/mL, 2.5 mg of tirzepatide is 0.5 mL, or 50 units. At 2.5 mg/mL, 0.25 mg of semaglutide is 0.1 mL, or 10 units.
So a unit count never carries over between drugs or vials. The mg to units calculator handles any strength.
Free calculator
Semaglutide Calculator. Convert a semaglutide dose in mg to mL and U-100 units for any vial, with the Ozempic and Wegovy label schedules.
Free calculator
Tirzepatide Calculator. Convert a tirzepatide dose in mg to mL and U-100 units, with the Zepbound and Mounjaro label schedule.
Are compounded semaglutide and tirzepatide still allowed?
Compounding is when a pharmacy makes its own version of a drug. It spread during the shortages, which are now over.
Pharmacies may copy an approved drug more freely while it is on the FDA shortage list. The FDA statement on compounding as GLP-1 supply stabilized says the tirzepatide shortage was declared resolved on October 2, 2024 (confirmed December 19, 2024) and the semaglutide shortage on February 21, 2025. Grace periods then ended for 503A pharmacies, which fill individual prescriptions, and 503B outsourcing facilities, larger FDA-registered compounders:
- Tirzepatide: for 503A, after a court denied an injunction on March 5, 2025; for 503B, on March 19, 2025.
- Semaglutide: for 503A, after a court denied an injunction on April 24, 2025; for 503B, on May 22, 2025.
In April 2026 the FDA said neither drug is on the shortage list or the 503B bulks list (bulk ingredients outsourcing facilities may use). A 503A pharmacy may not regularly compound copies of the brands unless a prescriber documents a significant difference for an identified patient. On April 30, 2026, it proposed formally excluding both drugs from the bulks list; we found no final decision as of October 14, 2026.
Compounded is not FDA-approved
The FDA does not review compounded drugs for safety, effectiveness or quality before sale. Their strength and labeling can differ from the brands, so ask your prescriber and pharmacist exactly what you were dispensed.
Frequently Asked Questions
Is tirzepatide stronger than semaglutide?
Not in a way the mg numbers can show. Tirzepatide doses are larger in mg because it is a different molecule. In SURMOUNT-5, average weight loss at 72 weeks was 20.2% with tirzepatide and 13.7% with semaglutide, but that is a group average from one open-label trial. Your prescriber can explain what it means for you.
Can you take semaglutide and tirzepatide together?
The labels advise against it. Wegovy and Zepbound each say use with any other GLP-1 receptor agonist is not recommended, and tirzepatide already acts on the GLP-1 receptor. Any move from one drug to the other is a decision to make with your prescriber.
Is 10 units of semaglutide the same as 10 units of tirzepatide?
No. A U-100 unit is 0.01 mL, so the mg in 10 units depends on the vial concentration: 0.25 mg at 2.5 mg/mL, but 2 mg at 20 mg/mL. Never reuse a unit count across drugs or vials. The semaglutide calculator and tirzepatide calculator show the math for your own vial.
How long do semaglutide and tirzepatide stay in your body?
Half-life is the time it takes for the blood level to fall by half. Semaglutide has a half-life of about 1 week, and the Wegovy label says it stays in the circulation for about 5 to 7 weeks after the last 2.4 mg or 7.2 mg dose. Tirzepatide has a shorter half-life, about 5 days.
Is Rybelsus the same drug as Ozempic?
Both contain semaglutide for type 2 diabetes, but Rybelsus (3, 7 and 14 mg) is a daily tablet and Ozempic injection is a weekly shot. Since 2026 the Ozempic name also covers a newer 1.5, 4 and 9 mg tablet. The label says Rybelsus and Ozempic tablets are not substitutable mg for mg.
Is compounded semaglutide or tirzepatide the same as the brand?
No. Compounded versions are not FDA-approved or reviewed for safety, effectiveness or quality. Both shortages were declared resolved, and the grace periods ended in 2025. Strengths vary by pharmacy, so check the mg/mL on any vial; the doses per vial calculator shows how many doses one holds.
Sources and References
- New England Journal of Medicine, via PubMed. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), 2025
- New England Journal of Medicine, via PubMed. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2), 2021
- DailyMed, U.S. National Library of Medicine. Zepbound (tirzepatide) injection: prescribing information (revised 8/2026)
- DailyMed, U.S. National Library of Medicine. Mounjaro (tirzepatide) injection: prescribing information (revised 8/2026)
- DailyMed, U.S. National Library of Medicine. Wegovy (semaglutide) injection and tablets: prescribing information (revised 6/2026)
- DailyMed, U.S. National Library of Medicine. Ozempic (semaglutide) injection: prescribing information (revised 5/2026)
- U.S. Food and Drug Administration. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (updated 4/2026)