Semaglutide vs tirzepatide vs retatrutide: receptors, half-life and status compared
Semaglutide, tirzepatide and retatrutide are the three incretin-based peptides researchers ask about most. They differ in which hormone receptors they activate, how far they are through regulation, and how much clinical evidence exists. This page compares the molecules for laboratory and educational purposes. It is not treatment guidance.
- Semaglutide activates the GLP-1 receptor only. Approved as Ozempic, Wegovy and Rybelsus.
- Tirzepatide activates GIP and GLP-1 receptors. Approved as Mounjaro and Zepbound.
- Retatrutide activates GIP, GLP-1 and glucagon receptors. Investigational and still in Phase 3 trials.
- Research-grade powders of all three are not the approved medicines and may only be sold for laboratory research.
Side-by-side comparison
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Receptors activated | GLP-1 | GIP + GLP-1 | GIP + GLP-1 + glucagon |
| Developer | Novo Nordisk | Eli Lilly | Eli Lilly |
| Approved brands | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound | None (investigational) |
| Regulatory status (US/UK/EU) | Approved, prescription only | Approved, prescription only | Not approved; Phase 3 |
| Molecular weight | 4113.58 g/mol | 4813.45 g/mol | ≈4731 g/mol |
| Half-life | About 7 days | About 5 days | About 6 days (Phase 1 data) |
| Half-life extension | C18 fatty diacid side chain binds albumin | C20 fatty diacid side chain binds albumin | Fatty diacid side chain binds albumin |
| Key trial programmes | SUSTAIN, STEP | SURPASS, SURMOUNT | TRIUMPH (Phase 3) |
| WADA | Permitted | Permitted | Not approved; may fall under S0 |
Receptor targets: one, two or three
All three are synthetic peptides modelled on gut hormones. Semaglutide is a GLP-1 analogue. Tirzepatide is built on a GIP backbone and also activates the GLP-1 receptor. Retatrutide adds glucagon-receptor activity, which is studied for its effect on energy expenditure and liver fat. More targets do not automatically mean a better research tool; they make results harder to attribute to a single pathway.
What head-to-head data exist?
In the SURMOUNT-5 trial, published in 2025, tirzepatide produced greater average weight reduction than semaglutide over 72 weeks in adults with obesity. Retatrutide has not yet been compared head-to-head with either in a published Phase 3 trial; its strongest published evidence so far is a Phase 2 study in the New England Journal of Medicine (2023).
Research-grade powder vs approved medicines
Ozempic, Wegovy, Mounjaro and Zepbound are manufactured and tested to medicine standards. Research-grade powders sold online are different products, and FDA has issued warning letters to sellers who market them for people. If you source any of these for a laboratory, insist on a batch-specific certificate of analysis showing HPLC purity and mass-spectrometry identity. See each profile: semaglutide, tirzepatide, retatrutide.
Frequently asked questions
What is the difference between semaglutide, tirzepatide and retatrutide?
Semaglutide activates the GLP-1 receptor, tirzepatide activates GIP and GLP-1 receptors, and retatrutide activates GIP, GLP-1 and glucagon receptors. The first two are approved medicines; retatrutide is investigational.
Is retatrutide stronger than tirzepatide?
There is no published Phase 3 head-to-head trial yet, so this cannot be said reliably. Retatrutide adds glucagon-receptor activity, but it is still investigational.
Which has the longest half-life?
Semaglutide, at about 7 days. Retatrutide is about 6 days and tirzepatide about 5 days.
Is retatrutide FDA-approved?
No. As of 27 October 2026 it is still in Phase 3 trials.
Are GLP-1 drugs banned by WADA?
Semaglutide and tirzepatide are permitted. WADA has confirmed GLP-1 receptor agonists remain permitted on the 2027 list. Retatrutide is not yet approved and may fall under the S0 class.