In the only head-to-head trial, tirzepatide reduced body weight more than semaglutide: 20.2% against 13.7% over 72 weeks. Retatrutide has not been placed alongside either of them in a single trial, but in a separate phase 3 study it produced a reduction of up to 25.0%.
Three molecules, three differences: the number of receptors, the strength of the effect on weight and the legal status. Semaglutide acts on one receptor, GLP-1. Tirzepatide combines two, GLP-1 and GIP. Retatrutide covers three, adding the glucagon receptor. The wider the set of receptors, the higher the average weight reduction in trials and the more side effects reported.
This article puts the trial data and the legal status side by side. The mechanism of incretins itself is covered in the article on how semaglutide, tirzepatide and retatrutide affect body weight.
Which peptide gives the largest weight reduction?
The highest average reduction belongs to retatrutide: 25.0% over 80 weeks at the 12 mg dose. Tirzepatide at 15 mg reached 20.9% over 72 weeks, and semaglutide at 2.4 mg about 15% over roughly two years. The semaglutide and tirzepatide figures come from the SURMOUNT-1 trial and the STEP programme, and the retatrutide figure from the phase 3 TRIUMPH-1 trial.
What did the only head-to-head trial show?
The single direct comparison in this group is SURMOUNT-5. It covered 751 people with obesity without diabetes, who for 72 weeks took the maximum tolerated dose of either tirzepatide or semaglutide, injected under the skin once a week.
Tirzepatide reduced body weight by 20.2% and semaglutide by 13.7%, a statistically significant difference. Waist circumference fell by 18.4 cm in the tirzepatide group and by 13.0 cm in the semaglutide group.
Retatrutide took part in no such comparison. Setting its 25.0% against the other two figures means comparing separate trials with different participants and different observation periods. Treat that number as an indication of direction, not the result of a contest.
The three molecules in a table
| Feature | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Receptors | GLP-1 | GLP-1 and GIP | GLP-1, GIP and glucagon |
| Main trial | STEP programme | SURMOUNT-1 | TRIUMPH-1, phase 3 |
| Average weight reduction | about 15% over about 2 years | 20.9% over 72 weeks | 25.0% over 80 weeks |
| Head-to-head data | SURMOUNT-5: tirzepatide 20.2% against semaglutide 13.7% over 72 weeks | none | |
| Status in Poland | prescription: Ozempic, Wegovy | prescription: Mounjaro | not approved for sale |
The table shows a direction, not a ranking from a single experiment. More receptors go together with a higher average weight reduction and with a larger number of side effects.
How do the side effects differ?
All three are dominated by gastrointestinal symptoms: nausea, vomiting, diarrhoea and constipation. The differences show up in the trial data, though they do not come from one comparison.
In SURMOUNT-5, 5.6% of people in the semaglutide group and 2.7% in the tirzepatide group stopped treatment because of gastrointestinal symptoms. In the retatrutide trial, at the highest dose, 42.4% of participants reported nausea, 32.0% diarrhoea, 26.1% constipation and 25.3% vomiting. Between 4.1% and 11.3% stopped treatment because of side effects, depending on dose.
The retatrutide figures concern higher doses and a different group than the semaglutide and tirzepatide comparison. No direct comparison of tolerability across all three exists.
Which of these is legal to buy?
Semaglutide and tirzepatide are prescription medicines. Semaglutide is sold as Ozempic, approved for type 2 diabetes, and as Wegovy, approved for obesity and for overweight with comorbidities. Tirzepatide has one product registered in Poland, Mounjaro. Retatrutide is not approved for sale and remains in phase 3 clinical trials.
The same names appear online on preparations labelled “for research”. That label does not change the legal status of the substance and gives the buyer no guarantee of quality, composition or safety of the kind required for a registered medicine.
In our shop the three molecules are available only as research material: semaglutide, tirzepatide and retatrutide. They are not sold for human use, the cart and the checkout are in English, and prices are shown in Polish zloty. Purchase and import rules are set out on the legal warning page.
Frequently asked questions
Is tirzepatide more effective than semaglutide?
In SURMOUNT-5 tirzepatide reduced body weight by 20.2% and semaglutide by 13.7% over 72 weeks, a statistically significant difference. That was the only direct comparison of the two in people with obesity without diabetes.
Is retatrutide better than tirzepatide?
They have not been tested in a single trial. Retatrutide reached up to 25.0% in TRIUMPH-1 and tirzepatide 20.9% in SURMOUNT-1, but the groups, doses and observation periods differed, so this is not a direct comparison.
Which of the three can be bought legally?
Semaglutide and tirzepatide are available legally only on prescription, as Ozempic, Wegovy and Mounjaro. Retatrutide is not approved for sale in any form.
Does one of them cause fewer side effects?
In SURMOUNT-5 fewer people stopped treatment because of gastrointestinal symptoms on tirzepatide (2.7%) than on semaglutide (5.6%). The retatrutide data come from a separate trial at higher doses, so they cannot be compared directly.
Why do sources quote different numbers for the same trial?
Because trials report results under more than one statistical approach. For TRIUMPH-1, one method gives 25.0% at the highest dose and another 28.3%; both describe the same study.
Where the figures in this article come from
The head-to-head result comes from the SURMOUNT-5 trial as described by the American College of Cardiology, published in the New England Journal of Medicine in 2025 (volume 393, pages 26 to 36). The figures for SURMOUNT-1 and the STEP programme come from the introduction to the SURMOUNT-3 trial in PubMed Central, reference PMC10667099. The retatrutide results from TRIUMPH-1 were reported by The Pharmaceutical Journal in May 2026. Legal status was described by Gazeta Prawna on 26 August 2026 and by Receptomat in its version of 22 July 2026. All pages were checked on 31 August 2026.