Tirzepatide produced more weight loss than semaglutide in the one head-to-head obesity trial: 20.2% versus 13.7% of body weight at 72 weeks in SURMOUNT-5. In type 2 diabetes, tirzepatide also beat semaglutide 1 mg on A1c and weight in SURPASS-2. They are different drugs. Semaglutide acts on one receptor, GLP-1. Tirzepatide acts on two, GLP-1 and GIP. Both are once-weekly shots with similar stomach side effects. If you are new to the drug, read our tirzepatide guide first.
Key takeaways
- Semaglutide (Wegovy, Ozempic) is a GLP-1 receptor agonist. Tirzepatide (Zepbound, Mounjaro) is a dual GIP and GLP-1 receptor agonist.
- SURMOUNT-5: tirzepatide -20.2% versus semaglutide -13.7% at 72 weeks in adults with obesity without diabetes.
- SURPASS-2: tirzepatide 5, 10 and 15 mg lowered A1c by 2.01, 2.24 and 2.30 points versus 1.86 for semaglutide 1 mg, with more weight loss at every dose.
- Both drugs list stomach effects as the most common side effects; the tirzepatide label puts nausea, diarrhea, vomiting and constipation at the top.
- Compounded semaglutide and compounded tirzepatide are not FDA approved and are not interchangeable with Wegovy, Ozempic, Zepbound or Mounjaro.
What is the difference between semaglutide and tirzepatide?
The difference is the receptor list. Both drugs copy gut hormones that tell your brain you are full, slow how fast your stomach empties, and help your pancreas release insulin when blood sugar is high. Semaglutide copies one hormone, GLP-1. Tirzepatide copies two, GLP-1 and GIP. GIP stands for glucose-dependent insulinotropic polypeptide, a second gut hormone. Acting on both receptors is the working explanation for why tirzepatide produced more weight loss in the head-to-head trial, though the trial itself measured outcomes, not mechanism.
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Receptors | GLP-1. | GLP-1 and GIP. |
| Weight management brand | Wegovy. | Zepbound. |
| Type 2 diabetes brand | Ozempic. | Mounjaro. |
| How often | Once weekly injection. | Once weekly injection. |
| Tirzepatide maximum dose | Not applicable. | 15 mg once weekly. |
| Head-to-head weight loss (SURMOUNT-5, 72 weeks) | -13.7%. | -20.2%. |
| Other tirzepatide-only indication | None. | Zepbound: moderate to severe obstructive sleep apnea in adults with obesity (approved December 20, 2024). |
Source: Zepbound and Mounjaro prescribing information (DailyMed); SURMOUNT-5, Aronne et al., NEJM 2025.
Tirzepatide vs semaglutide for weight loss: SURMOUNT-5
SURMOUNT-5 is the trial that answers "which is better for weight loss" directly. It randomized adults with obesity and without diabetes to tirzepatide or semaglutide for 72 weeks, on top of diet and exercise counseling.
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Take the Assessment →| SURMOUNT-5 outcome at 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Mean change in body weight | -20.2% | -13.7% |
Source: SURMOUNT-5, Aronne et al., NEJM 2025.
For context, tirzepatide's own placebo-controlled trial, SURMOUNT-1, showed -15.0% at 5 mg, -19.5% at 10 mg and -20.9% at 15 mg versus -3.1% for placebo over 72 weeks. The SURMOUNT-5 tirzepatide result sits inside that range. Semaglutide's 13.7% is a large loss too. "Better on average" is not "works for everyone"; some people respond more to one drug than the other, and tolerance matters as much as the average.
Semaglutide vs tirzepatide in type 2 diabetes: SURPASS-2
SURPASS-2 compared three doses of tirzepatide with semaglutide 1 mg (the Ozempic dose used in the trial) over 40 weeks in adults with type 2 diabetes.
| SURPASS-2 arm (40 weeks) | A1c change (percentage points) | Weight change (kg) |
|---|---|---|
| Tirzepatide 5 mg | -2.01 | -7.6 |
| Tirzepatide 10 mg | -2.24 | -9.3 |
| Tirzepatide 15 mg | -2.30 | -11.2 |
| Semaglutide 1 mg | -1.86 | -5.7 |
Source: SURPASS-2, Frias et al., NEJM 2021.
Every tirzepatide dose beat semaglutide 1 mg on both measures. Note the comparator: 1 mg is a diabetes dose of semaglutide, not the higher Wegovy dose. SURMOUNT-5 is the fairer weight loss comparison.
Dosing: how the schedules differ
Tirzepatide follows one label schedule for Zepbound and Mounjaro. Start at 2.5 mg once weekly for 4 weeks. Increase in 2.5 mg steps after at least 4 weeks on the current dose. Maintenance doses are 5, 10 or 15 mg; 15 mg is the maximum. The drug can be injected at any time of day, with or without food, in the abdomen, thigh or upper arm. Semaglutide for weight management (Wegovy) is also titrated in steps, from 0.25 mg weekly up to a 2.4 mg weekly maintenance dose.
| Tirzepatide label step | Dose | Minimum time before the next step |
|---|---|---|
| Start | 2.5 mg once weekly | 4 weeks |
| Step 2 | 5 mg | At least 4 weeks |
| Step 3 | 7.5 mg | At least 4 weeks |
| Step 4 | 10 mg | At least 4 weeks |
| Step 5 | 12.5 mg | At least 4 weeks |
| Maximum | 15 mg | Stay here if tolerated |
Source: Zepbound and Mounjaro prescribing information (DailyMed).
The milligram numbers are not comparable between the two drugs. Tirzepatide 15 mg is not "six times" semaglutide 2.4 mg; they are different molecules with different potencies. Never convert a dose from one to the other on your own. Switching is a prescriber decision, and the Zepbound label says coadministration with any GLP-1 receptor agonist is not recommended.
Tirzepatide vs semaglutide side effects
Both drugs share the same family of side effects because they act on the same gut pathway. The Zepbound label lists these as the most common adverse reactions, at least 5% and more than placebo: nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection site reactions, fatigue, hypersensitivity reactions, burping, hair loss and reflux. Both drug labels also carry a boxed warning about thyroid C-cell tumors seen in rats.
| SURMOUNT-1 adverse event (tirzepatide, 72 weeks) | Placebo | 5 mg | 10 mg | 15 mg |
|---|---|---|---|---|
| Nausea | 9.5% | 24.6% | 33.3% | 31.0% |
| Diarrhea | 7.3% | 18.7% | 21.2% | 23.0% |
| Vomiting | 1.7% | 8.3% | 10.7% | 12.2% |
| Constipation | 5.8% | 16.8% | 17.1% | 11.7% |
| Stopped drug for adverse events | 2.6% | 4.3% | 7.1% | 6.2% |
Source: SURMOUNT-1, Jastreboff et al., NEJM 2022.
Does tirzepatide have fewer side effects than semaglutide? We do not print semaglutide side effect rates because the semaglutide trial data are not in our verified source list, and comparing rates across different trials is unreliable anyway. SURMOUNT-5 was the head-to-head trial; its primary result was weight, and the summary numbers we can cite are the weight numbers above. What both labels agree on: stomach effects are the main issue, they cluster during dose increases, and most are mild to moderate.
Semaglutide vs tirzepatide cost
| Product | Price | Notes |
|---|---|---|
| FormBlends compounded semaglutide | $99 first month, then $190 a month; $165 with Subscribe & Save | Plans: 3 months $399, 6 months $714, 12 months $1,188. |
| FormBlends compounded tirzepatide | $149 first month, then $239 a month; $214 with Subscribe & Save | Plans: 3 months $627, 6 months $1,194, 12 months $2,148. |
| Zepbound vials, LillyDirect self-pay | $299 (2.5 mg), $399 (5 mg), $499 (7.5 mg), $699 (10, 12.5, 15 mg) a month | Eli Lilly published pricing, accessed September 4, 2026; as little as $25 with commercial coverage and the savings card. |
Source: FormBlends pricing (verified September 5, 2026); Eli Lilly LillyDirect pricing (accessed September 4, 2026).
FormBlends prices do not change with dose, shipping and injection supplies are included, lab work is not, and there is no membership fee. Wegovy and Ozempic prices are not printed because they are not in our verified list. See the pricing page for both compounded drugs.
What this means for compounded tirzepatide
Every number on this page comes from trials of the branded drugs. Compounded semaglutide and compounded tirzepatide are not FDA approved, are not interchangeable with Wegovy, Ozempic, Zepbound or Mounjaro, and have no trial data of their own. If you are choosing between the two compounded drugs, the trial results are the best guide to what the molecules do, but a licensed provider decides which, if either, is appropriate for you. Start with the assessment.
Frequently Asked Questions
Is tirzepatide better than semaglutide?
For weight loss on average, yes. In SURMOUNT-5, tirzepatide produced 20.2% mean weight loss versus 13.7% for semaglutide at 72 weeks. In SURPASS-2, tirzepatide beat semaglutide 1 mg on A1c and weight. Individual response and tolerance still vary.
Is semaglutide the same as tirzepatide?
No. Semaglutide acts on the GLP-1 receptor only. Tirzepatide acts on both the GLP-1 and GIP receptors. They are different molecules sold under different brand names: Wegovy and Ozempic for semaglutide, Zepbound and Mounjaro for tirzepatide.
Which has fewer side effects, semaglutide or tirzepatide?
Both cause mainly stomach side effects, and both carry the same boxed warning. We do not have verified semaglutide side effect rates to compare, and cross-trial comparisons are unreliable. In SURMOUNT-1, nausea affected 24.6% to 33.3% of people on tirzepatide versus 9.5% on placebo.
What is the tirzepatide vs semaglutide dosage for weight loss?
Tirzepatide starts at 2.5 mg weekly and rises in 2.5 mg steps to a maximum of 15 mg. Wegovy semaglutide rises from 0.25 mg to a 2.4 mg weekly maintenance dose. The milligrams are not comparable between the drugs.
Should I take semaglutide or tirzepatide?
That is a prescriber decision. Tirzepatide has the stronger average weight loss result, semaglutide has a longer track record, and cost, coverage and tolerance all matter. Do not take both; the Zepbound label says coadministration with any GLP-1 receptor agonist is not recommended.
Is compounded semaglutide or compounded tirzepatide better?
The compounded products have no trial data of their own. The branded trial results above are the best guide to what the molecules do. Compounded semaglutide and tirzepatide are not FDA approved and are not interchangeable with the brands; a licensed provider decides.
Sources
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), Aronne et al., New England Journal of Medicine, 2025.
- Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2), Frias et al., New England Journal of Medicine, 2021.
- Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), Jastreboff et al., New England Journal of Medicine, 2022.
- Zepbound (tirzepatide) prescribing information, DailyMed, National Library of Medicine, revised 08/2026.
- Mounjaro (tirzepatide) prescribing information, DailyMed, National Library of Medicine, revised 08/2026.
- FormBlends pricing, Form Blends LLC, verified September 5, 2026.
- FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss, U.S. Food and Drug Administration.
Next steps
For the diabetes-brand version of this question, read tirzepatide vs Ozempic; for the weight-brand version, is Wegovy the same as tirzepatide. If you are thinking about using both, read can you take semaglutide and tirzepatide in the same week, and for every price, the tirzepatide cost guide. Browse the tirzepatide hub for every other tirzepatide question. Talk to a clinician before you choose or switch. Compounded tirzepatide is not FDA approved and is not interchangeable with Zepbound or Mounjaro; a licensed provider decides whether it is appropriate for you.
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