Semaglutide, tirzepatide and retatrutide are three peptides that mimic gut hormones known as incretins. What separates them is the number of receptors they act on: semaglutide stimulates one (GLP-1), tirzepatide two (GLP-1 and GIP) and retatrutide three (GLP-1, GIP and the glucagon receptor). In clinical trials, each widening of that set comes with a larger average reduction in body weight.
The scale of the difference is clear. Semaglutide at 2.4 mg reduces body weight by roughly 15% over two years, tirzepatide at 15 mg by 20.9% over 72 weeks, and retatrutide at 12 mg by 25.0% over 80 weeks in a phase 3 trial. All figures come from the studies described below, with sources given.
Semaglutide and tirzepatide are prescription medicines. Retatrutide is not approved for sale anywhere.
The sections that follow describe the mechanism of each molecule, the trial data and the legal status. This is not a set of instructions for use, because that is a decision for a doctor.
What are incretins and the GLP-1, GIP and glucagon receptors?
Incretins are hormones the gut releases after a meal to prepare the body for incoming nutrients. The two main ones are GLP-1, glucagon-like peptide 1, and GIP, gastric inhibitory polypeptide. Semaglutide, tirzepatide and retatrutide are peptides, short chains of amino acids, that attach to the same receptors as the natural hormones and set off the same pathways.
What does the GLP-1 receptor do?
Stimulating the GLP-1 receptor helps the pancreas release the right amount of insulin when blood sugar is high, slows gastric emptying and reduces appetite. The effect on body weight comes mostly from the last two: a meal stays in the stomach longer and appetite drops. Semaglutide acts on this receptor alone.
What does the GIP receptor add?
GIP is the second incretin. Tirzepatide stimulates the GIP receptor and the GLP-1 receptor at the same time, which is why it is called a dual agonist. Combining both pathways in the SURMOUNT-1 trial was associated with weight reduction of around 20% in people with obesity. Why that second receptor matters is covered in the article on tirzepatide and its two receptors.
Why does retatrutide add the glucagon receptor?
Retatrutide adds a third target, the glucagon receptor, which is why it is described as a triple agonist of the GIP, GLP-1 and glucagon receptors. The glucagon component is what sets retatrutide apart from the other two molecules. Its share of the final effect on weight has not yet been fully quantified. Until the full phase 3 results are published, retatrutide remains an investigational molecule, not a medicine.
How does semaglutide work and what did the weight trials show?
Semaglutide is a GLP-1 receptor agonist which, in obesity trials, reduced body weight by roughly 15% over about two years, against 2 to 3% on placebo. The result applies to people with obesity or overweight without diabetes, at a dose of 2.4 mg injected under the skin once a week.
The dose is raised gradually over several weeks to limit side effects. The most common are gastrointestinal: nausea, vomiting, diarrhoea and constipation.
Semaglutide is sold under two names. Ozempic is approved for type 2 diabetes, and Wegovy for the treatment of obesity and of overweight with comorbidities, at a body mass index of at least 30 or at least 27. Both require a prescription.
How does tirzepatide work and how does it differ from semaglutide?
Tirzepatide is a dual agonist of the GLP-1 and GIP receptors which, in the SURMOUNT-1 trial, reduced body weight by 20.9% over 72 weeks, against 3.1% on placebo. The trial covered people with obesity or overweight without diabetes, and the result applies to the 15 mg dose. Compared with semaglutide, it differs by the additional GIP pathway and by a higher average reduction in body weight.
The dosing schedule is the same: a subcutaneous injection once a week, with slow escalation. The side effect profile is also similar and dominated by gastrointestinal symptoms.
The tirzepatide product registered in Poland is Mounjaro, approved for type 2 diabetes and for obesity and overweight with metabolic complications, available on prescription.
How does retatrutide work and what do the phase 3 trials show?
Retatrutide is a triple agonist of the GIP, GLP-1 and glucagon receptors which, in the phase 3 TRIUMPH-1 trial, reduced body weight by an average of 25.0% over 80 weeks at the 12 mg dose. The 9 mg dose gave 23.7%, the 4 mg dose 17.6%, and placebo 3.9%. The trial covered 2,339 people with obesity without diabetes, and in the subgroup continuing to 104 weeks the reduction reached around 30%.
Side effects were more frequent than with the other two molecules and again concerned the digestive tract. 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% of people stopped treatment because of side effects, depending on dose, against 4.9% on placebo. The full trial programme is described in the article on retatrutide and the phase 3 results.
Retatrutide is not approved for sale in the European Union or the United States. It remains a molecule in clinical trials.
Semaglutide, tirzepatide and retatrutide compared
| Feature | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Receptors | GLP-1 | GLP-1 and GIP | GLP-1, GIP and glucagon |
| Average weight reduction | about 15% over about 2 years (2.4 mg) | 20.9% over 72 weeks (15 mg) | 25.0% over 80 weeks (12 mg) |
| Placebo group in those trials | 2 to 3% | 3.1% | 3.9% |
| Trial | STEP programme | SURMOUNT-1 | TRIUMPH-1, phase 3 |
| Administration | subcutaneous, once weekly | subcutaneous, once weekly | subcutaneous, once weekly in trials |
| Status in Poland | prescription: Ozempic, Wegovy | prescription: Mounjaro | not approved for sale |
The figures come from different trials over different periods, so the table is not a head-to-head comparison of the three molecules in one experiment. It shows a direction: more receptors, a higher average reduction in body weight and more side effects.
Why are two of these prescription medicines and the third unavailable?
Semaglutide and tirzepatide are dispensed on prescription. Pharmacies dispense them on a prescription written after assessment of indications and contraindications. Retatrutide has not completed registration, so pharmacies do not dispense it.
Online, the same names appear on preparations described as "for research" or "research use only". That label does not change the legal status of the substance and gives the buyer no guarantee of the quality, safety or composition expected of a registered medicine. A research preparation may contain an uncertain amount of active substance, impurities, or be counterfeit.
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 euro.
Before reaching for any of these molecules, check its current legal status in your country and consult a doctor. Our rules on purchase and import are set out on the legal warning and safety page.
Frequently asked questions
Which of these peptides gives the largest weight reduction?
In the available trials the highest average reduction was recorded for retatrutide: 25.0% over 80 weeks at the 12 mg dose. Tirzepatide reached 20.9% over 72 weeks and semaglutide about 15% over roughly two years. These come from different trials over different periods, so they are not a head-to-head comparison.
Are semaglutide and tirzepatide prescription medicines?
Yes, as medicines. Pharmacies dispense semaglutide as Ozempic and Wegovy and tirzepatide as Mounjaro on prescription. In our shop both molecules are available as research material.
How does a research peptide differ from a registered medicine?
A preparation described as research material is not subject to the quality control required of a medicinal product. It may contain an uncertain amount of active substance, impurities, or be counterfeit, and its labelling does not change the legal status of the substance.
Is retatrutide available as a medicine yet?
Not yet. As of the publication of this article, retatrutide remains in phase 3 clinical trials and is not registered as a medicine in the European Union or the United States.
What are the most common side effects of GLP-1 peptides?
Gastrointestinal symptoms dominate: nausea, vomiting, diarrhoea and constipation. In the retatrutide trial, 42.4% of participants on the highest dose reported nausea.
Where the figures in this article come from
The figures for semaglutide and tirzepatide come from the introduction to the SURMOUNT-3 trial in PubMed Central, reference PMC10667099, which reports a 15% weight reduction for semaglutide 2.4 mg and 20.9% for tirzepatide 15 mg in SURMOUNT-1. The retatrutide results from the phase 3 TRIUMPH-1 trial were reported by The Pharmaceutical Journal in May 2026. The legal status of semaglutide was described by Gazeta Prawna on 26 August 2026 and that of tirzepatide by Receptomat in its version of 22 July 2026. All pages were checked on 31 August 2026.
Sources
- Jastreboff AM, Aronne LJ, Ahmad NN et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1 trial). New England Journal of Medicine, 2022, 387(3): 205-216. https://doi.org/10.1056/NEJMoa2206038
- Wadden TA, Chao AM, Machineni S et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine, 2023, 29(11): 2909-2918. https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/
- Phase III retatrutide study demonstrates 30% weight loss. The Pharmaceutical Journal, May 2026. https://pharmaceutical-journal.com/article/news/phase-iii-retatrutide-study-demonstrates-30-weight-loss
- Ozempic (semaglutide). European public assessment report (EPAR), European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic
- Mounjaro (tirzepatide). European public assessment report (EPAR), European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro