The class page above sorts these compounds by receptor count. This goes one level down: what each receptor does when activated, what the trials behind tirzepatide and retatrutide measured and in whom, what the EU authorisation record says with dates, and how to read a comparison between them without being misled.
Three receptors, three different jobs
GLP-1 and GIP are the two incretin hormones proper: gut peptides released after a meal that raise insulin secretion only while glucose is high. GLP-1 also slows gastric emptying and reduces food intake (Müller TD et al. Glucagon-like peptide 1 (GLP-1). Mol Metab 2019. PMID 31767182). Those are the effects semaglutide relies on, and why a single-receptor compound produces weight loss at all.
GIP’s own contribution is harder to isolate. It comes from K cells in the upper gut, GLP-1 from L cells lower down; in type 2 diabetes the pancreas responds poorly to GIP while GLP-1 keeps its insulin-raising and glucagon-suppressing effects, which is why GLP-1 became the parent of the first incretin medicines, and GIP also acts on fat tissue and bone (Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab 2018. PMID 29364588). What GIP adds inside one molecule with GLP-1 is known only from tirzepatide’s trials; no GIP-only medicine exists (what is tirzepatide?).
Glucagon is not an incretin. It is insulin’s counter-regulatory hormone and raises blood glucose; its case in a weight-management compound rests on its other actions, higher energy expenditure, lower lipids and less food intake, shown largely in preclinical work, alone and with GLP-1 agonism (Habegger KM et al. The metabolic actions of glucagon revisited. Nat Rev Endocrinol 2010. PMID 20957001). Retatrutide was built on that design (what is retatrutide?): in obese mice, the calorie-intake reduction from the GIP and GLP-1 receptors was augmented by glucagon-receptor-driven energy expenditure, and the molecule was built with balanced glucagon and GLP-1 activity but more GIP activity (Coskun T et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab 2022. PMID 35985340).
What the trials measured, and in whom
SURMOUNT-1 randomised 2,539 adults with obesity or overweight and no diabetes to tirzepatide or placebo for 72 weeks including a 20-week dose-escalation period; mean weight change at week 72 was −15.0%, −19.5% and −20.9% at 5, 10 and 15 mg against −3.1% on placebo, and the commonest adverse events were gastrointestinal, mostly during escalation (Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022. PMID 35658024; NCT04184622). In the 1,032 who also had prediabetes, treatment continued to 176 weeks: weight change was −12.3%, −18.7% and −19.7% against −1.3%, and 1.3% on tirzepatide had developed type 2 diabetes against 13.3% on placebo (Jastreboff AM et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med 2025. PMID 39536238).
The retatrutide trial behind the interest is Phase 2: 338 adults, 48 weeks, placebo-controlled, with mean weight change of −24.2% at the 12 mg dose against −2.1% on placebo; gastrointestinal events were dose-related, and a dose-dependent rise in heart rate peaked at 24 weeks (Jastreboff AM, Kaplan LM, Frías JP et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med 2023. PMID 37366315).
The two head-to-heads, and the one that has not happened
Dual against single has been tested directly, twice (tirzepatide vs semaglutide). SURPASS-2 randomised 1,879 patients with type 2 diabetes to tirzepatide at 5, 10 or 15 mg or semaglutide at 1 mg for 40 weeks on top of metformin; tirzepatide was noninferior and superior on glycated haemoglobin, 2.01 to 2.30 percentage points against 1.86, with a further 1.9 to 5.5 kg of weight loss (Frías JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021. PMID 34170647; NCT03987919). The comparator there was the 1 mg diabetes dose. SURMOUNT-5 closed that gap: 751 adults with obesity and no diabetes, maximum tolerated tirzepatide (10 or 15 mg) against maximum tolerated semaglutide (1.7 or 2.4 mg) for 72 weeks, with weight change of −20.2% against −13.7% (Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025. PMID 40353578). Both were open-label. Triple against dual has never been tested head-to-head; that pairing is set out at retatrutide vs tirzepatide.
Receptors, evidence and the EU record, side by side
| Compound | Receptors | Strongest evidence in print | EU marketing authorisation |
|---|
| Semaglutide | GLP-1 | Completed Phase 3 programmes; comparator in SURPASS-2 and SURMOUNT-5 | Ozempic (type 2 diabetes); Wegovy (weight management) |
| Tirzepatide | GIP + GLP-1 | Completed Phase 3 in obesity and in type 2 diabetes | Mounjaro, both indications |
| Retatrutide | GIP + GLP-1 + glucagon | Phase 2 in obesity; one Phase 3 in type 2 diabetes | None |
Semaglutide was authorised as Ozempic on 8 February 2018 for type 2 diabetes (European Medicines Agency. Ozempic EPAR.) and as Wegovy on 6 January 2022 for weight management (European Medicines Agency. Wegovy EPAR.). Tirzepatide was authorised as Mounjaro on 15 September 2022, and that one authorisation now covers both type 2 diabetes and weight management; there is no separate EU product for the weight indication (European Medicines Agency. Mounjaro EPAR.).
Retatrutide holds no EU marketing authorisation. Its obesity programme, TRIUMPH, comprises four Phase 3 trials in over 5,800 participants (Giblin K et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab 2026. PMID 41090431); the lead trial, TRIUMPH-1 (NCT05929066), enrolled 2,335, is listed as completed on 30 April 2026, and has no results posted. The first Phase 3 result in print is in a different population: TRANSCEND-T2D-1, a 40-week trial in 537 people with type 2 diabetes, reported larger glycated-haemoglobin reductions than placebo at every dose and weight change of −15.3% at 12 mg against −2.6% (Bajaj HS et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet 2026. PMID 42250575). A diabetes trial does not stand in for the obesity programme, which has not reported.
How to read a cross-trial comparison
The receptor count tells you what a molecule was designed to do; the trial, what it did in a defined group over a defined time; the authorisation, what a regulator has assessed. A compound can score highest on the first and lowest on the other two, as retatrutide does today. Before accepting any figure, attach five things: the phase, since Phase 2 selects doses and Phase 3 is what regulators assess; the population, since obesity and type 2 diabetes were separate programmes above; the duration, since 24, 40, 48, 72 and 176 weeks are not points on one curve; the comparator and its dose; and whether the analysis counted people who stopped treatment. Apply those five to the 24.2% and the 20.9% and the gap between them stops looking like the important difference.
What we stock, and what the certificate shows
Three pens in our range belong to this class: TIRZEPATIDE 60, 60 mg in 3 ml and currently on pre-order, and RETATRUTIDE 32 and RETATRUTIDE 64, 32 mg and 64 mg in the same 3 ml, one compound at two concentrations. Semaglutide is not in our range. Each pen comes pre-loaded, so there is nothing to reconstitute (pen vs vial). Every batch is tested by an independent laboratory for identity by mass spectrometry, purity by HPLC and sterility; the certificate, showing the purity figure and the cartridge concentration, is reached from the QR code on the pen or the index at /coa. None of these pens is the authorised medicine: for tirzepatide one exists and a clinician can prescribe it; for retatrutide none exists anywhere (why these compounds are not EMA-authorised). Either compound is also listed with NAD+ as the Lean Stack or the Advanced Lean Stack, and the whole weight-loss goal is on one page.
