This is the highest-stakes comparison on the site, and the one where the marketing runs furthest ahead of the paperwork. People searching it usually want to know whether the newer compound is simply the better one. The mechanistic story — one receptor, then two, then three — makes that feel obvious. The regulatory story does not, and it is the one that actually separates these three. Here is what each has behind it.
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Evidence tier | ApprovedFDA-approved for at least one specific indication. Approval is for THAT indication only - it says nothing about the uses discussed in community protocols. | ApprovedFDA-approved for at least one specific indication. Approval is for THAT indication only - it says nothing about the uses discussed in community protocols. | Human trialsSubstantial human clinical trial data exists, but the compound is not approved for the use discussed here. |
| Regulatory status | FDA-approved | FDA-approved | Investigational - in trials |
| Researched for | GLP-1 receptor agonist. The most clinically validated peptide here — large randomised trials for glycaemic control and weight. | Dual GLP-1 and GIP receptor agonist, with large trial data behind both of its approved indications. | Investigational triple agonist — GLP-1, GIP and glucagon receptors at once. Phase 2 figures are the largest in the class so far. |
| What people use it for | Substantial weight loss; strong appetite suppression; reduced “food noise”; improved blood sugar and metabolic markers. | Weight loss and glycaemic control; appetite suppression. Reported by users as stronger than single-agonist GLP-1s. | Rapid and large-scale weight loss; strong visceral and liver fat reduction; solid appetite control. Often described as stronger than prior GLP-1s. |
| Reported figure | 5 mg vial + 1 mL water = 5,000 mcg/mL 1 mg → 0.20 mL · 20 unitsOne reported reference at that reconstitution — not a standard. | None given.The approved label titrates 2.5 mg to 15 mg weekly under supervision — a prescriber-managed range, not a reference figure. | 10 mg vial + 2 mL water = 5,000 mcg/mL 1 mg → 0.20 mL · 20 unitsOne reported reference at that reconstitution — not a standard. |
| Route | Subcutaneous, once weekly. | Subcutaneous, once weekly. Label titration runs under prescriber supervision. | Subcutaneous, once weekly by convention. No company-published dosing schedule exists. |
| Calculator entry | Yes — Semaglutide calculator | Yes — Tirzepatide calculator | Yes — Retatrutide calculator |
Scroll the table sideways →
Two of these are approved medicines and one is not, and no amount of receptor arithmetic changes that.
Semaglutide is graded here as “the most clinically validated compound on this site. Approved as Ozempic (type 2 diabetes) and Wegovy (chronic weight management), backed by large randomised trials.” The same entry adds a caveat worth reading twice: compounded semaglutide is a different supply route from the approved product. Trial data belongs to the approved product, not automatically to whatever arrives in a vial.
Tirzepatide is “approved as Mounjaro (type 2 diabetes) and Zepbound (obesity), with large trial data behind both. Label titration runs 2.5 mg up to 15 mg weekly under supervision.” That titration range is wide by design, it is prescriber-managed, and it is the reason this site publishes no single reference figure for it.
Retatrutide is the one people are most excited about and the one with the least settled behind it: “Investigational triple agonist in Phase 3 (TRIUMPH programme). Real, large, ongoing human trials — but not approved anywhere, and no company-published dosing schedule exists.” Those are real trials, not hand-waving. They are also not finished, and there is no manufacturer titration schedule to follow — every schedule circulating is reconstructed from trial protocols or community convention.
So the gradient runs approved, approved, investigational — while the hype gradient runs in the opposite direction. Both facts are true at once, and holding them together is most of what this comparison is for.
Education only. This page is educational. Most compounds referenced are not approved for human use, and a "research use only" label carries no legal status of its own.
A comparison, not a recommendation. Nothing on this page ranks one compound above another or suggests running either. Where a figure appears, it is one reported reference at the reconstitution shown — not a standard, not a clinical dose.
Reference ranges. Any amounts mentioned are values commonly reported in published research and community protocols, provided for reference only. Reported does not mean established, safe, or effective.
Not medical advice. Nothing here constitutes medical advice, diagnosis, or treatment. Several of these are prescription medicines in Canada and the US, and several are approved nowhere at all. Consult a qualified healthcare professional before beginning any protocol.