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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

Head-to-head evidence
SURMOUNT-5, 751 adults
Tirzepatide record
FDA label; 2 sourced dose rows
Semaglutide record
FDA label; 2 sourced dose rows

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.

SURMOUNT-5 — mean weight change at week 72Mean weight change
2Exact values 2 rows in the data table
SURMOUNT-5 — mean weight change at week 72
Trial armMean 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.

Tirzepatide and Semaglutide side by side: drug class, brand names, FDA approval, strongest source, dosing, half-life, boxed warning, reported reactions and typical vial sizes
PropertyTirzepatideSemaglutide
Drug classGIP/GLP-1 dual receptor agonistGLP-1 receptor agonist
Brand namesZepbound, MounjaroWegovy, Ozempic, Rybelsus
FDA approvalApprovedApproved
Strongest sourceFDA labelFDA label
Dosing5–15 mg once weekly (5, 10, or 15 mg)1.7–2.4 mg once weekly
Half-life5 days7 days
Boxed warningRisk of thyroid C-cell tumorsRisk of thyroid C-cell tumors
Reactions on record1515
Typical vial sizes5 mg · 10 mg · 15 mg · 30 mg · 60 mg2 mg · 5 mg · 10 mg
4Comparison detailsMechanism, side effects, regulatory context, and source records

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.

On both records
  • Nausea
  • Diarrhea
  • Constipation
  • Vomiting
  • Abdominal pain
  • Dyspepsia (indigestion)
  • reactions where injected
  • Fatigue
  • Acute pancreatitis
  • Gallbladder disease (cholelithiasis)
  • Hypoglycemia (with insulin or a sulfonylurea)
  • Acute kidney injury (from dehydration)
  • Diabetic retinopathy complications
  • Severe hypersensitivity reactions
Recorded for Tirzepatide only
  • Decreased appetite
Recorded for Semaglutide only
  • Headache

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.

The full regulatory tracker →

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

An approved tirzepatide label exists — beyond tirzepatide vs semaglutide.

Wegovy vs zepbound, the counterpart to tirzepatide vs semaglutide

SURMOUNT-5 studied 751 adults for 72 weeks. This sits beyond tirzepatide vs semaglutide.

The semaglutide page behind tirzepatide vs semaglutide

Semaglutide has an approved label, separate from tirzepatide vs semaglutide.

Work out a tirzepatide draw, one side of tirzepatide vs semaglutide

Tirzepatide vial sizes: 5 mg, 10 mg, 15 mg, 30 mg and 60 mg. These do not come from tirzepatide vs semaglutide.

The semaglutide calculator behind tirzepatide vs semaglutide

The semaglutide vial presets are 1 mL and 2 mL of water. They belong to this tool, not to the tirzepatide vs semaglutide page.

Tirzepatide dosing in full, beyond tirzepatide vs semaglutide

Tirzepatide has an approved label. This is separate from tirzepatide vs semaglutide.

Every semaglutide step, outside tirzepatide vs semaglutide

2 sourced semaglutide values, each traceable without going via tirzepatide vs semaglutide.

Mixing math for any peptide, with tirzepatide vs semaglutide as one example

Concentration, units per draw and draws per vial, including Tirzepatide vs semaglutide

The dated regulatory page behind tirzepatide vs semaglutide

Every entry cites its source. It comes from the Federal Register or fda.gov, with tirzepatide vs semaglutide as context

Where tirzepatide vs semaglutide sits among the comparisons

Molecule and product comparisons stay separate, including Tirzepatide vs semaglutide

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?

The trial gives a percentage, not a deadline. After 72 weeks, average weight loss was 20.2% on tirzepatide and 13.7% on semaglutide.

Neither arm was tracked to a pound target, and both were open-label — everyone knew which drug they had.

Why would a doctor prescribe semaglutide instead of tirzepatide?

The approved uses differ. Semaglutide labels include certain heart and kidney benefits that tirzepatide labels do not.

Tirzepatide’s labels carry neither of those. Coverage and device also decide plenty of prescriptions, and neither is a clinical judgment about the molecule.

What makes you less sick, semaglutide or tirzepatide?

SURPASS-2 compared symptom counts directly, and the results were close. Nausea affected 17 to 22 in 100 on tirzepatide and 18 on semaglutide. Vomiting affected 6 to 10 and 8.

Serious problems of any kind separated further: 5 to 7 in 100 against 3. That trial ran in adults with type 2 diabetes, so it does not describe people taking either drug for weight.

Do you lose more muscle on semaglutide or tirzepatide?

Nobody has published this. SURMOUNT-5 measured body weight and waist size, and did not scan anyone to separate fat from muscle.

That means any figure circulating for muscle loss on either drug is not coming from the head-to-head trial.

3primary sources, each with the day we read it — open the documents used on this page