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Comparison · sourced side by side
Tirzepatide vs Semaglutide
One trial has compared tirzepatide and semaglutide directly: SURMOUNT-5. It ran 72 weeks in 751 adults. Average weight change was -20.2% on tirzepatide and -13.7% on semaglutide. Both groups went up to the highest dose they could tolerate.
FDA label FDA label
What matters first
Is there a head-to-head trial?
Yes. SURMOUNT-5 was a phase 3b open-label randomized trial in adults with obesity, without diabetes. It compared both drugs in the same study. Everyone went up to the highest dose they could handle. The result therefore reflects how the drugs were used, not a matched dose on paper.
| Trial arm | Mean weight change |
|---|---|
| Tirzepatide (highest dose reached) | −20.2% |
| Semaglutide (highest dose reached) | −13.7% |
Source: Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med 2025;393:26-36 · retrieved 2026-08-12. Randomized head-to-head; 751 participants over 72 weeks. Trial results describe averages across a study population, not an individual outcome.
- Mean waist-circumference change: −18.4 cm with tirzepatide vs −13.0 cm with semaglutide.
- More people on tirzepatide reached each weight-loss mark: 10%, 15%, 20% and 25%.
- Both drugs were raised step by step to the highest dose each person could handle, using their own label schedules.
Side by side
Every row is read from the two records, and every clinical figure carries its own citation. Where a value does not exist, the row says so instead of guessing one.
| Property | Tirzepatide | Semaglutide |
|---|---|---|
| Drug class | GIP/GLP-1 dual receptor agonist | GLP-1 receptor agonist |
| Brand names | Zepbound, Mounjaro | Wegovy, Ozempic, Rybelsus |
| FDA approval | Approved | Approved |
| Strongest source | FDA label | FDA label |
| Dosing | 5–15 mg | 1.7–2.4 mg |
| Half-life | ≈ 5 days | ≈ 7 days |
| Boxed warning | Risk of thyroid C-cell tumors | Risk of thyroid C-cell tumors |
| Reactions on record | 15 | 15 |
| Typical vial sizes | 5 mg · 10 mg · 15 mg · 30 mg · 60 mg | 2 mg · 5 mg · 10 mg |
4Comparison details
How they work differently
Tirzepatide is a gip/glp-1 dual receptor agonist. Semaglutide is a glp-1 receptor agonist. They switch on different signals in the body. That can change both benefits and side effects. Sharing one target does not make two drugs interchangeable.
More targets do not guarantee a better result. They change both the effect and the side-effect pattern. A clinician weighs those tradeoffs for each person.
Side effects compared
Side effects below come from each compound’s own page, grouped by whether both records list them. A side effect on one list only means the other record does not carry it — not that it never happens.
Regulatory status compared
Tirzepatide
FDA-approved as branded pens.
Compounded tirzepatide now faces tight limits. FDA declared the shortage over in late 2024. It has proposed dropping tirzepatide from the 503B bulks list.
That leaves one narrow lane: 503A compounding for a named patient with a documented clinical need.
Semaglutide
FDA has approved the branded pens, and the oral tablet Rybelsus.
FDA declared the semaglutide shortage resolved in February 2025. Mass compounding has wound down since. FDA has also proposed dropping it from the 503B bulks list.
Keep reading
A comparison is a summary of two records. These are the pages themselves, plus the tools and schedules the rows above are read from.
Tirzepatide on its own page, outside tirzepatide vs semaglutide
Wegovy vs zepbound, the counterpart to tirzepatide vs semaglutide
The semaglutide page behind tirzepatide vs semaglutide
Work out a tirzepatide draw, one side of tirzepatide vs semaglutide
The semaglutide calculator behind tirzepatide vs semaglutide
Tirzepatide dosing in full, beyond tirzepatide vs semaglutide
Every semaglutide step, outside tirzepatide vs semaglutide
Mixing math for any peptide, with tirzepatide vs semaglutide as one example
The dated regulatory page behind tirzepatide vs semaglutide
Where tirzepatide vs semaglutide sits among the comparisons
Common questions
Which is more effective, tirzepatide or semaglutide?
In SURMOUNT-5, tirzepatide came out ahead on average weight change — -20.2% against -13.7% over 72 weeks. That is an average across a trial group, not a prediction for you, and it is only one of the things a prescriber weighs.
Can these two be compared using their separate trial results?
Not reliably. Separate trials can include different people, run for different lengths of time, and measure different things. Only a head-to-head trial measures the difference.
Are the side-effect profiles the same?
They overlap a lot — 14 side effects appear on both records, mostly stomach-related. The lists also differ. Evidence from an approved label is stronger than an early trial report.
Is either one approved by the FDA?
Both are approved and both have prescribing labels, so their dosing and side-effect figures come from regulatory documents.
Does a newer compound mean a better one?
No. A newer drug often has less evidence, a shorter safety record, and no approved label. The strength of the evidence above is more useful than age alone.
Can someone switch between them?
A clinician decides that based on the reason for treatment, the current dose, and how the first drug felt. A prescribing clinician should advise on any treatment change.
Questions readers ask
How long does it take to lose 20 lbs on tirzepatide?
Why would a doctor prescribe semaglutide instead of tirzepatide?
What makes you less sick, semaglutide or tirzepatide?
Do you lose more muscle on semaglutide or tirzepatide?
- Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med 2025;393:26-36retrieved 2026-08-12Human trial
- Zepbound (tirzepatide) — FDA-approved Prescribing Informationretrieved 2026-07-22FDA label
- Wegovy (semaglutide) — FDA-approved Prescribing Information (DailyMed)retrieved 2026-08-20FDA label