Tirzepatide stimulates two incretin receptors at once: GLP-1 and GIP. The GLP-1 receptor alone is responsible for insulin secretion, slower gastric emptying and reduced appetite. Adding the GIP receptor lowers blood sugar further in trials and suppresses appetite more strongly.
In practice this shows up in the result. In a head-to-head trial, tirzepatide produced greater weight reduction than a GLP-1 agonist on its own. The mechanism of the incretins is described in the pillar article on GLP-1, and a direct comparison of the three molecules in a separate side-by-side article.
What does the GLP-1 receptor do?
Stimulating the GLP-1 receptor prompts the pancreas to secrete insulin and brings down raised blood sugar. On top of that it slows gastric emptying and suppresses appetite. Those last two effects account for the impact on body weight.
Insulin secretion after stimulation of this receptor depends on the glucose level. That means the effect appears when blood sugar is raised and fades when it is low. Hence the profile of this class of drugs, in which action on the GLP-1 receptor alone rarely leads to hypoglycaemia.
What does the GIP receptor add?
GIP is the second gut incretin. Tirzepatide is a synthetic peptide acting simultaneously on the GLP-1 receptor and the GIP receptor. According to the reviews, dual stimulation lowers raised blood sugar more clearly than a GLP-1 agonist alone and reduces the patient's appetite more strongly.
Newer work describes two routes for that effect. Stimulating the GIP receptor activates appetite-suppressing circuits in the brain and increases heat production, that is thermogenesis. This adds a mechanism the GLP-1 receptor does not have on its own, and it explains why two molecules acting on one pathway give a different result from one molecule acting on two.
The GIP receptor paradox: stimulate or block?
The same receptor is today the target of two opposing strategies, and both reduce body weight. It sounds like a contradiction, but the explanation is simpler than it seems.
Stimulating the GIP receptor, the tirzepatide route, works through the appetite-suppressing circuits mentioned above and through thermogenesis. Blocking the same receptor, studied in other molecules, in turn strengthens the GLP-1 receptor signal and removes the effect of the body's own GIP on fat deposition. A review published in the journal Appetite in 2026 sums this up in one sentence: both pharmacological stimulation and blockade of the signal from the GIP receptor lower body weight.
For a reader this means one practical thing. The bare fact that a molecule "acts on GIP" does not yet say in which direction or with what result. What counts is the direction of action and the outcome of the trial, not the name of the receptor in a product description.
Do two receptors give a better effect on body weight?
In the available data, yes. In SURMOUNT-5, the only direct comparison of these two drugs, tirzepatide reduced body weight by 20.2 per cent and semaglutide by 13.7 per cent over 72 weeks, a statistically significant difference. The trial covered 751 people with obesity and without diabetes.
The earlier SURMOUNT-1 trial, run without a semaglutide arm, gave a mean reduction of 20.9 per cent over 72 weeks at the highest dose. Waist circumference fell in the comparative trial by 18.4 cm in the tirzepatide group and by 13.0 cm in the semaglutide group.
Is tirzepatide better tolerated?
The side-effect profile is close to that of other drugs in this class and is dominated by the digestive tract. Nausea and diarrhoea appear in up to about 10 per cent of patients; vomiting and heartburn are reported less often. A drop in appetite is also common, and it works in favour of the intended weight reduction.
In SURMOUNT-5, fewer people discontinued treatment because of gastrointestinal symptoms in the tirzepatide group than in the semaglutide group, 2.7 per cent against 5.6 per cent. These numbers come from one trial and one group of participants, so they are not a rule for every patient.
What is the status of tirzepatide?
The United States Food and Drug Administration approved tirzepatide in May 2022 for the treatment of type 2 diabetes. It is sold under the name Mounjaro in diabetes and Zepbound in the obesity indication. In Poland, where this shop is based, Mounjaro is registered and dispensed on prescription.
A peptide of the same name offered as a reagent is not a substitute for a registered medicine and carries no guarantee of composition or purity of the kind a medicine has. The whole picture is set out in the article on the legal status of peptides.
What is in the shop?
In this shop tirzepatide is stocked strictly as research material, on the tirzepatide page. It is not sold for human use.
The other molecules in this class are collected in the weight loss peptides category, among them semaglutide and retatrutide. The third of them is described in the article on retatrutide and the phase 3 trials. The terms of purchase are set out on the legal warning page.
Frequently asked questions
How does tirzepatide differ from semaglutide in the way it acts?
Semaglutide stimulates only the GLP-1 receptor, while tirzepatide stimulates the GLP-1 receptor and the GIP receptor at the same time. That is why it is called a dual agonist.
Why does tirzepatide need a second receptor?
According to the reviews, stimulating the GIP receptor alongside the GLP-1 receptor lowers raised blood sugar more clearly and reduces appetite more strongly than action on GLP-1 alone. It also adds thermogenesis, that is increased heat production.
Why does blocking the GIP receptor also lower body weight?
Reviews from 2026 describe both directions as effective. Stimulation works through appetite-suppressing circuits and thermogenesis, while blockade strengthens the GLP-1 receptor signal and removes the effect of the body's own GIP on fat deposition.
By how much did tirzepatide lower body weight in trials?
In SURMOUNT-5 by 20.2 per cent over 72 weeks, against 13.7 per cent on semaglutide. In SURMOUNT-1 the mean reduction at the highest dose was 20.9 per cent over 72 weeks.
Is tirzepatide an approved medicine?
Yes. The United States Food and Drug Administration approved it in May 2022. In Poland, Mounjaro is registered and dispensed on prescription.
What are the most common side effects of tirzepatide?
Gastrointestinal symptoms dominate. Nausea and diarrhoea occur in up to about 10 per cent of patients, vomiting and heartburn less often.
Where this information comes from
The description of the mechanism of tirzepatide, the role of the GLP-1 receptor, the contribution of the GIP receptor, the date and indication of approval by the United States Food and Drug Administration and the most common side effects come from the tirzepatide chapter in the StatPearls database on NCBI Bookshelf. The SURMOUNT-5 result comes from a review by the American College of Cardiology, with publication in the New England Journal of Medicine in 2025; the figures of 20.2 per cent against 13.7 per cent, the change in waist circumference and the discontinuation rates come from there. The SURMOUNT-1 result comes from the introduction to the SURMOUNT-3 trial in PubMed Central, PMC10667099. The status of Mounjaro in Poland was described by the Receptomat service, version of 22 July 2026. These pages were checked on 31 August 2026.
The description of the two opposing strategies towards the GIP receptor, including the part played by appetite-suppressing circuits and thermogenesis under stimulation and the strengthening of the GLP-1 signal under blockade, comes from the paper by Gao SX and Borner T, "One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy", Appetite 2026, PMID 42492687, and from the paper by Nauck M and co-authors, "Clinical Potential of GIP in Type 2 Diabetes and Obesity", Diabetes Care 2026, PMID 41973737. The abstracts were read through Europe PMC on 7 September 2026.
Sources
- Tirzepatide. StatPearls, NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK585056/
- Aronne LJ, Horn DB, le Roux CW et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5 trial). New England Journal of Medicine, 2025, 393(1): 26-36. https://doi.org/10.1056/NEJMoa2416394
- 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/
- Gao SX, Borner T. One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy. Appetite, 2026, 227: 108723. https://doi.org/10.1016/j.appet.2026.108723
- Nauck M, Gribble F, Reimann F et al. Clinical Potential of GIP in Type 2 Diabetes and Obesity. Diabetes Care, 2026, 49(8): 1308-1317. https://doi.org/10.2337/dci25-0141