Semaglutide vs tirzepatide
In SURMOUNT-5, the one head-to-head obesity trial, average weight change over 72 weeks was −20.2% on tirzepatide and −13.7% on semaglutide. Semaglutide acts on the GLP-1 receptor; tirzepatide acts on GIP and GLP-1. Both are FDA-approved, and semaglutide also has a large heart-outcome trial (SELECT).[1,2]
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At a glance
How do Semaglutide and Tirzepatide compare?
SURMOUNT-5 and SURPASS-2 compared the two drugs directly. SURMOUNT-5 was open-label (people knew which drug they were on) and was funded by Eli Lilly, which makes tirzepatide. The other rows come from separate placebo-controlled trials.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Receptors | SemaglutideGLP-1 | TirzepatideGIP and GLP-1 |
| Brand names | SemaglutideOzempic, Wegovy (Novo Nordisk) | TirzepatideMounjaro, Zepbound (Eli Lilly) |
| FDA status[3,4] | SemaglutideApproved: Wegovy for weight management (2021), Ozempic for type 2 diabetes | TirzepatideApproved: Mounjaro for type 2 diabetes (2022), Zepbound for weight management (2023) |
| How often | SemaglutideOnce a week | TirzepatideOnce a week |
| Head-to-head weight change (SURMOUNT-5, 72 weeks)[1] | Semaglutide−13.7% | Tirzepatide−20.2% |
| Head-to-head waist change (SURMOUNT-5)[1] | Semaglutide−13.0 cm | Tirzepatide−18.4 cm |
| Against placebo[5,6] | SemaglutideSTEP 1: −14.9% at 68 weeks on 2.4 mg (placebo −2.4%) | TirzepatideSURMOUNT-1: −20.9% at 72 weeks on 15 mg (placebo −3.1%) |
| Top weekly dose in those trials[5,6] | Semaglutide2.4 mg | Tirzepatide15 mg |
| Stopped because of side effects[5,6] | SemaglutideSTEP 1: 4.5% for stomach side effects (placebo 0.8%) | TirzepatideSURMOUNT-1: 4.3% to 7.1% (placebo 2.6%) |
| Heart-outcome trial[2] | SemaglutideSELECT: 20% lower risk of heart attack, stroke or cardiovascular death | TirzepatideNone among the sources on this page |
SURMOUNT-5: weight change at 72 weeks[1]
Phase 3b, open-label · 751 adults with obesity, no diabetes · highest tolerated dose of each
Receptors
Which receptors does each one act on?
Tap a drug to compare. Each extra receptor adds another hormone signal. More receptors does not by itself mean safer or better.
Which leads to more weight loss, semaglutide or tirzepatide?
Tirzepatide, in the trial that compared them. SURMOUNT-5 gave 751 adults with obesity the highest dose they could tolerate of either drug for 72 weeks. Average weight change was −20.2% on tirzepatide and −13.7% on semaglutide, and waist size fell by 18.4 cm versus 13.0 cm.[1]
How do semaglutide and tirzepatide work differently?
Semaglutide mimics one gut hormone, GLP-1, which slows stomach emptying, reduces appetite and helps the pancreas release insulin when blood sugar is high. Tirzepatide activates the GLP-1 receptor and also the receptor for a second gut hormone, GIP. According to its FDA label, this lowers appetite and food intake.[4]
Which has more side effects?
The side effects are the same kind. In SURMOUNT-5 the most common adverse events in both groups were gastrointestinal, mostly mild to moderate, and mostly during dose increases. In separate trials, 4.5% stopped semaglutide for stomach side effects (STEP 1) and 4.3% to 7.1% stopped tirzepatide for side effects (SURMOUNT-1).[1,5,6]
Is 2.4 mg of semaglutide the same as 15 mg of tirzepatide?
No. They are different molecules, so milligrams cannot be compared between them. Semaglutide's top weekly dose for weight management is 2.4 mg and tirzepatide's is 15 mg. How many syringe units that is depends on your vial and how much water you added, which the calculators work out.[7,4]
Work out the units for your vial
Milligrams are not comparable between compounds, and the units on your syringe depend on your vial and how much water you add. Each guide has a chart for its common vial sizes.
Questions
Common questions
Is tirzepatide stronger than semaglutide?
In the two head-to-head trials, tirzepatide led to more weight loss. In SURMOUNT-5 (obesity) it was −20.2% versus −13.7% at 72 weeks. In SURPASS-2 (type 2 diabetes) every tirzepatide dose lowered HbA1c and weight more than semaglutide 1 mg.
Are semaglutide and tirzepatide both FDA-approved?
Yes. Semaglutide is approved as Ozempic (type 2 diabetes) and Wegovy (weight management, 2021). Tirzepatide is approved as Mounjaro (type 2 diabetes, 2022) and Zepbound (weight management, 2023). Research powders of either are not the approved products.
Who paid for the head-to-head trial?
SURMOUNT-5 was funded by Eli Lilly, the maker of tirzepatide, and it was open-label, meaning participants knew which drug they were taking. It was published in the New England Journal of Medicine in 2025.
Does tirzepatide have heart-outcome data like semaglutide?
Semaglutide has SELECT, a trial of 17,604 adults in which 2.4 mg cut the risk of heart attack, stroke or cardiovascular death by 20%. The sources we cite for tirzepatide do not include a heart-outcome trial.
Do semaglutide and tirzepatide carry the same warning?
Tirzepatide's FDA label carries a boxed warning about thyroid C-cell tumours seen in rodents, and says not to use it with a personal or family history of medullary thyroid carcinoma or MEN 2. Read the current label for each medicine and talk to a clinician.
Sources
- 1.Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5)
Aronne LJ et al. N Engl J Med 2025;393:26-36 · Human trial - 2.Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT)
Lincoff AM et al. N Engl J Med 2023;389:2221-2232 · Human trial - 3.Wegovy approval letter
FDA. Wegovy (semaglutide) NDA 215256 approval letter, June 2021 · FDA - 4.Zepbound label
FDA. Zepbound (tirzepatide) prescribing information, 2024 · FDA - 5.Once-weekly semaglutide in adults with overweight or obesity (STEP 1)
Wilding JPH et al. N Engl J Med 2021;384:989-1002 · Human trial - 6.Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)
Jastreboff AM et al. N Engl J Med 2022;387:205-216 · Human trial - 7.Wegovy label
FDA. Wegovy (semaglutide) prescribing information, 2025 · FDA
Last reviewed Oct 4, 2026. Education only, not medical advice. PepDose sells no peptides.