The difference is how many receptors each one activates. Semaglutide acts on GLP-1 alone. Tirzepatide adds GIP. Retatrutide adds glucagon on top of both. That is also the order of how much is known about them: semaglutide has the deepest evidence base, retatrutide the thinnest.
| Retatrutide from $80 | Tirzepatide from $140 | Semaglutide from $130 | |
|---|---|---|---|
| Receptors | GIP + GLP-1 + Glucagon | GIP + GLP-1 | GLP-1 |
| Agonist type | Triple | Dual | Single |
| Developer | Eli Lilly | Eli Lilly | Novo Nordisk |
| Trial stage | Phase 2 published | Approved medicine | Approved medicine |
| Australian status | Not approved | Registered (Mounjaro) | Registered (Ozempic, Wegovy) |
| Published data | Thinnest | Extensive | Most extensive |
| Strengths stocked | 5–30MG | 10–20MG | 10–20MG |
These three are often described as versions of the same idea getting progressively stronger. That is not quite right. They are three different mechanisms: adding a receptor is not turning up a dial, it recruits a different signalling pathway with its own effects and its own unknowns.
Semaglutide targets the GLP-1 receptor only, which makes it the cleanest tool for isolating GLP-1 effects. Tirzepatide adds GIP, and is GIP-biased rather than balanced. Retatrutide adds glucagon receptor agonism, which is associated with energy expenditure rather than intake signalling — a different arm of metabolism entirely.
GLP-1 and GIP are incretins — gut hormones released after eating, involved in insulin release and satiety signalling. Glucagon is usually framed as insulin's opposite, but glucagon receptor agonism is also associated with increased energy expenditure and hepatic fat handling, which is why it appears in a metabolic research compound at all.
Whether GIP agonism helps was genuinely unsettled before tirzepatide: both GIP agonism and GIP antagonism had been proposed as strategies. Tirzepatide is the compound that made the agonist case, and its own receptor balance is lopsided — considerably higher affinity for GIP than for GLP-1.
Semaglutide has the deepest evidence base of the three, with the SUSTAIN and STEP programmes behind it and cardiovascular outcome data from SELECT in 2023. Tirzepatide has the SURPASS and SURMOUNT programmes, plus later work in sleep apnoea and heart failure.
Retatrutide has two phase 2 trials published in 2023 and no completed phase 3 anywhere. That gap matters when reading claims about it: everything known is early-stage, and there is no long-term safety or outcome data at all.
Semaglutide and tirzepatide are registered prescription medicines here, as Ozempic, Wegovy and Mounjaro. Retatrutide is registered nowhere in the world. Research-grade material is a separate thing from any of those products: it is a laboratory reagent, not a medicine, and OzPeptides supplies all three strictly for in-vitro and laboratory research.
Semaglutide came first and set the template. It is a GLP-1 analogue modified at position 8 to resist DPP-4, the enzyme that clears native GLP-1 within minutes, and carrying a fatty-acid chain that binds albumin and stretches its half-life to about a week. Everything after it is an answer to the question of what else could be added.
Tirzepatide answered that with GIP. It is built on the GIP sequence rather than the GLP-1 one, which is the detail most summaries skip: it is a GIP peptide taught to activate the GLP-1 receptor, not the reverse. Its affinity remains considerably higher for GIP, so describing it as a balanced dual agonist overstates the symmetry.
Retatrutide added glucagon. That is a larger conceptual jump than adding a second incretin, because glucagon receptor agonism pushes on energy expenditure and hepatic fat handling rather than on intake signalling. Balancing three receptor activities in one molecule — enough of each to matter, not so much that one dominates — is the hard part of the design, and it is what the published dose-finding work spends its pages on.
Semaglutide's record runs from SUSTAIN in type 2 diabetes through STEP in obesity to SELECT in 2023, which reported cardiovascular outcomes in people with overweight or obesity and established cardiovascular disease. That last one matters for a reason beyond the headline: outcome trials measure events, not surrogate markers, and very few compounds in any category have one.
Tirzepatide has SURPASS for type 2 diabetes and SURMOUNT for obesity, with SURPASS-2 the head-to-head against semaglutide. Later work extended to obstructive sleep apnoea and to heart failure with preserved ejection fraction in people with obesity — indications that follow the metabolic effect rather than repeat it.
Retatrutide has two phase 2 trials, both published in 2023: a 48-week obesity trial in the New England Journal of Medicine and a type 2 diabetes trial in The Lancet. Phase 2 establishes dose and signal. It does not establish long-term safety, rare adverse events, or durability, and no phase 3 has reported. Anyone comparing headline percentages across these three is comparing a 48-week phase 2 against completed phase 3 programmes, which is not a fair comparison in either direction.
All three are long peptides with lipid side chains, which makes them demanding syntheses and puts the same class of impurity in all three: truncated chains that stopped short, and deletion sequences missing a residue. These are what HPLC separates, and why a purity figure on a 39-residue peptide carries more information than the same figure on a tripeptide.
Retatrutide is the longest and the newest to manufacture at scale, so batch-to-batch consistency is the thing to watch. Semaglutide is the most widely produced and, for the same reason, the most widely counterfeited: material sold as semaglutide is a common place to find something that is not. Mass spectrometry is what separates a correct peptide backbone with the wrong acylation from the real thing, and neither appearance nor a purity percentage will do it.
Reconstitution arithmetic is identical across the three — a 10mg vial is 10mg whichever compound it holds — so the calculator applies to all of them without adjustment.
No published trial compares retatrutide against tirzepatide head to head, so any claim that one outperforms the other rests on cross-trial comparison, which is unreliable: different populations, different durations, different endpoints.
None of it tells you anything about research-grade material bought online, including ours. A trial establishes what a pharmaceutical-grade compound did in a controlled population; it says nothing about what is in a given vial. That is what batch testing is for, and it is a separate question from efficacy.
And none of it is a reason to use any of these compounds. They are sold here for laboratory research, they are not approved for human use in that form, and the trial literature is about registered medicines given under supervision.
If the question is about GLP-1 specifically, semaglutide is the cleaner instrument: one receptor, the deepest characterisation, and the compound every other result is measured against. Introducing a dual or triple agonist into a study designed to isolate GLP-1 effects adds variables rather than sensitivity.
If the question is what GIP contributes on top of GLP-1, tirzepatide is the tool that exists, with the caveat that its receptor balance is not even. And if the question involves glucagon receptor agonism alongside incretin signalling, retatrutide is currently the only compound of its kind — which is also why so little is settled about it.
We stock all three across seven strengths: retatrutide from 5MG to 30MG, tirzepatide and semaglutide at 10MG and 20MG. Each strength has its own page, its own batch and its own per-milligram price.
The published phase 2 data reports larger effects, but comparing across separate trials with different designs is not the same as a head-to-head result, and retatrutide has no phase 3 data at all.
To resist DPP-4, the enzyme that clears native GLP-1 within minutes. The fatty-acid chain that binds albumin is what extends its half-life to about a week.
No. It is built on the GIP sequence and taught to activate the GLP-1 receptor, which is the reverse of how it is usually described.
Semaglutide and tirzepatide are registered prescription medicines here. Retatrutide is not approved anywhere in the world.
Not from the published data. There is no head-to-head trial involving retatrutide, so any ranking rests on comparing across trials with different populations, durations and endpoints.
Semaglutide. SELECT, reported in 2023, measured cardiovascular events rather than surrogate markers. Neither tirzepatide nor retatrutide has an equivalent.
No. Its affinity is considerably higher for the GIP receptor, and published pharmacology describes its GLP-1 activity as comparatively weak in isolation.
Glucagon receptor agonism is associated with energy expenditure and hepatic fat handling, rather than the intake signalling the two incretin receptors govern.
The number of receptors each activates. Semaglutide acts on GLP-1 only, tirzepatide on GIP and GLP-1, and retatrutide on GIP, GLP-1 and glucagon.
Semaglutide, by a distance. Retatrutide has the least — two phase 2 trials and no completed phase 3.
It acts on an additional receptor, which is a different mechanism rather than a stronger version of the same one. No head-to-head phase 3 comparison has been published.
Semaglutide and tirzepatide are registered prescription medicines. Retatrutide is not approved anywhere. Research-grade material of any of the three is not a medicine.
This comparison summarises published research for educational purposes. It is not medical advice. OzPeptides products are sold for research and laboratory use only, not for human consumption. 18+ only.