In short
Retatrutide is a triple agonist (GIP, GLP-1, glucagon); tirzepatide is a dual agonist (GIP, GLP-1). In trials retatrutide showed the greater weight reduction (up to 24.2% in Phase 2, ~28% in Phase 3) but is not yet approved; tirzepatide is already approved as Mounjaro/Zepbound. This comparison covers published research data only (RUO).
What is Retatrutide?
Retatrutide is Eli Lilly’s investigational LY3437943, the first triple hormone receptor agonist, activating GIP, GLP-1 and glucagon receptors at once. It is given once weekly and is not approved by the FDA or EMA. The glucagon arm is what distinguishes it, being linked in research to higher energy expenditure and effects on liver fat.
Retatrutide (Eli Lilly, LY3437943) is an investigational triple-hormone-receptor agonist that simultaneously activates the GIP, GLP-1 and glucagon receptors, the first of its kind in obesity research. Molecular mass 4731.3 Da, half-life ~6 days from a C20 fatty-diacid modification.
What is Tirzepatide?
Tirzepatide is the approved dual agonist of GIP and GLP-1, sold as Mounjaro and Zepbound, and it is the molecule that showed dual receptor activation outperforms either pathway alone. In the SURMOUNT programme it reached up to 20.9 percent mean weight reduction, which is what made the triple agonist worth pursuing.
Tirzepatide (Eli Lilly, Mounjaro/Zepbound) is a dual agonist of GIP and GLP-1, already approved by the FDA and EMA. In the SURMOUNT trial it reached up to 20.9% mean weight reduction (15 mg).
Comparison table
The table compares them on the criteria that actually differ: number of receptors, half-life, trial weight reduction and regulatory status. Retatrutide adds a third receptor and roughly six days of half-life against tirzepatide’s five. The decisive row is approval, because one is a marketed medicine and the other is not.
| Criterion | Retatrutide | Tirzepatide |
|---|---|---|
| Receptors | GIP + GLP-1 + glucagon (triple) | GIP + GLP-1 (dual) |
| Half-life | ~6 days | ~5 days |
| Trial weight reduction | up to 24.2% (Ph 2) / ~28% (Ph 3) | up to 20.9% (SURMOUNT) |
| Dosing (trials) | 1–12 mg, once weekly | 5–15 mg, once weekly |
| Approval status | investigational, not approved | approved (Mounjaro/Zepbound) |
| Molecular mass | 4731.3 Da | ~4813.5 Da |
Trial data
In the Phase 2 trial retatrutide at 12 mg reached a mean weight reduction of up to 24.2 percent at 48 weeks (Jastreboff, NEJM 2023), against tirzepatide’s up to 20.9 percent in SURMOUNT. The comparison is indicative rather than direct, because these are separate trials with different populations and durations.
In the Phase 2 trial (Jastreboff et al., NEJM 2023, PubMed 37366315) retatrutide at 12 mg reached mean weight reduction of up to 24.2% at 48 weeks. The Phase 3 TRIUMPH trial confirmed ~28% over 80 weeks, the strongest GLP-1 effect reported to date. A network meta-analysis found 23.77% (retatrutide) vs 16.79% (tirzepatide).
Half-life & dosing
Both are given once weekly by subcutaneous injection. Retatrutide has a half-life of roughly six days from its C20 fatty diacid and albumin binding, tirzepatide roughly five. Both use gradual titration over several weeks, because gastrointestinal tolerability rather than efficacy is what limits the starting dose.
Both molecules are given once weekly subcutaneously. Retatrutide has a half-life of ~6 days (C20 fatty-diacid, albumin binding), tirzepatide ~5 days. Each titration step requires ≥ 4 weeks to reach steady state in trials.
Legal status
Retatrutide is not approved (FDA, EMA) – it is in Phase 3, with EMA approval expected no earlier than 2027–2028. Tirzepatide is approved (Mounjaro/Zepbound). At Molequa® both are offered exclusively as research peptides (RUO), not for human consumption.
FAQ
What is the main difference? Retatrutide activates three receptors (GIP/GLP-1/glucagon), tirzepatide two (GIP/GLP-1).
Which is stronger in trials? Retatrutide showed greater weight reduction, but direct head-to-head trials are pending.
Are both approved? No, only tirzepatide is approved; retatrutide is investigational.
Legal notice: Retatrutide and tirzepatide are offered exclusively for scientific laboratory research (RUO). They are not intended for human or animal consumption. This article summarizes published research data and is not medical advice.
