Key takeaways
- Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on the GIP and GLP-1 receptors.
- In SURMOUNT-5, a 72-week trial of FDA approved medicines, average weight change was -20.2% with tirzepatide and -13.7% with semaglutide. The trial was open-label and funded by Eli Lilly.
- Those results come from FDA approved Zepbound and Wegovy. They do not apply to compounded versions, which are not FDA approved.
- Both medicines carry a boxed warning about thyroid C-cell tumors seen in rodents.
- A licensed provider decides whether either medicine is appropriate for you.
What is the difference between tirzepatide and semaglutide?
Both are once-weekly injectable medicines that act on gut hormone receptors. Semaglutide acts on one receptor, GLP-1. Tirzepatide acts on two, GIP and GLP-1. FDA approved versions exist for each: Zepbound contains tirzepatide and Wegovy contains semaglutide. Both labels say not to combine the medicine with another GLP-1 receptor agonist.
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist [3]. Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist [2].
What did the head-to-head trial find?
In SURMOUNT-5, a 72-week trial of the FDA approved medicines, adults taking tirzepatide (Zepbound) had a larger average weight change than adults taking semaglutide (Wegovy). The trial enrolled 751 adults with obesity and no type 2 diabetes. It was open-label and funded by Eli Lilly, the maker of tirzepatide.
Each person was randomly assigned to one medicine at the maximum tolerated dose [1]. Open-label means participants and investigators knew which medicine was used.
| Measure at week 72 | Tirzepatide (Zepbound) | Semaglutide (Wegovy) |
|---|---|---|
| Average change in body weight | -20.2% | -13.7% |
| Average change in waist circumference | -18.4 cm | -13.0 cm |
More people in the tirzepatide group reached weight reductions of at least 10%, 15%, 20% and 25% [1]. The most common side effects in both groups were gastrointestinal. Most were mild to moderate and occurred mainly while the dose was being increased [1].
These figures come from trials of FDA approved Zepbound and Wegovy. They do not apply to compounded tirzepatide or compounded semaglutide. See the next section.
Do these results apply to compounded versions?
No. Results from trials of FDA approved products do not apply to compounded versions. Compounded tirzepatide and compounded semaglutide are not FDA approved, are not generic versions of Zepbound or Wegovy, and are not equivalent to them. The FDA does not review compounded drugs for safety, effectiveness or quality.
Source: [4]. A trial of one product does not show what a different product will do. Stackhaus Health prescriptions for these medicines are compounded and prepared by a state-licensed pharmacy for an individual patient.
What safety warnings do both medicines share?
Both carry a boxed warning about thyroid C-cell tumors seen in rodents. It is unknown whether either medicine causes these tumors, including medullary thyroid carcinoma (MTC), in humans. Both are contraindicated in people with a personal or family history of MTC or with multiple endocrine neoplasia syndrome type 2 (MEN 2).
Sources: [2][3]. Gastrointestinal side effects were the most common in the trial [1]. Because compounded medications are not FDA approved, complete information about how often side effects occur with them is limited.
Important safety information. Tell your provider if you are pregnant, planning a pregnancy or breastfeeding, and about all medications and health conditions. Your provider reviews your health history before prescribing. Do not use either medicine if you or a family member has had MTC, or if you have MEN 2.
Which one is right for you?
Your provider decides. Neither medicine is the right choice for every person. A licensed provider reviews your health history, current medications, other conditions and preferences. SURMOUNT-5 studied one group of adults for 72 weeks at maximum tolerated doses, so it cannot tell any one person which medicine fits them.
Eligibility, formulation, dosage and treatment decisions are made individually after a medical review.
How does it work at Stackhaus Health?
You complete a free online intake about your health history and goals. A licensed provider reviews it and decides whether compounded tirzepatide or semaglutide is appropriate, and in which form. Completing the intake does not guarantee a prescription. If prescribed, a state-licensed pharmacy prepares and ships it, and its name appears on your label.
See compounded tirzepatide, compounded semaglutide, all weight loss options, our pharmacy network and our editorial policy.
What research supports
- In one open-label trial of FDA approved medicines, average weight change at 72 weeks was larger with tirzepatide than with semaglutide [1].
- Both labels carry the same boxed warning about thyroid C-cell tumors seen in rodents [2][3].
What research does not show
- Whether these results apply to compounded tirzepatide or compounded semaglutide. Compounded versions have not been studied in trials like this one.
- A blinded head-to-head trial. SURMOUNT-5 was open-label and funded by the maker of tirzepatide [1].
- Results in people with type 2 diabetes. SURMOUNT-5 enrolled adults without it [1].
- Results beyond 72 weeks, or at doses below the maximum tolerated dose.
Frequently asked questions
How do tirzepatide and semaglutide compare in trials?
In SURMOUNT-5, a 72-week open-label trial of FDA approved Zepbound and Wegovy, average weight change was larger with tirzepatide. These results do not apply to compounded versions, and they do not show which medicine fits any one person.
Do the trial results apply to compounded tirzepatide or semaglutide?
No. Results from trials of FDA approved products do not apply to compounded versions.
Is compounded tirzepatide or semaglutide FDA approved?
No. Compounded medications are not FDA approved. FDA does not review them for safety, effectiveness or quality.
Is compounded tirzepatide a generic of Zepbound?
No. Compounded tirzepatide is not a generic version of, or equivalent to, Zepbound. The same is true of compounded semaglutide and Wegovy.
Who should not take tirzepatide or semaglutide?
Do not use either medicine if you or a family member has had medullary thyroid carcinoma (MTC), or if you have multiple endocrine neoplasia syndrome type 2 (MEN 2). Tell your provider if you are pregnant, planning a pregnancy or breastfeeding.
Can I take tirzepatide and semaglutide together?
Both drug labels say not to use the medicine together with another GLP-1 receptor agonist. Your provider decides what is appropriate for you.
What are the common side effects of tirzepatide and semaglutide?
In SURMOUNT-5, the most common side effects in both groups were gastrointestinal, such as nausea, diarrhea, vomiting and constipation. Most were mild to moderate and occurred mainly while the dose was being increased [1]. Tell your provider about any side effect that bothers you or does not go away.
Is tirzepatide or semaglutide safer?
SURMOUNT-5 was not designed to show that one medicine is safer than the other, and it does not apply to compounded versions. Both labels carry the same boxed warning about thyroid C-cell tumors seen in rodents [2][3]. Your provider weighs your health history and decides what is appropriate for you.
Who decides which medicine I get?
Your provider, after reviewing your health history and medications. Follow your prescription label.
References
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36. PMID: 40353578. DOI
- U.S. Food and Drug Administration. Zepbound (tirzepatide) prescribing information. FDALabel. View label
- Novo Nordisk Inc. Wegovy (semaglutide) prescribing information. DailyMed, National Library of Medicine. View label
- U.S. Food and Drug Administration. Compounding and the FDA: Questions and Answers. FDA
_logo_late_2025.svg){kind=logo}
