In short
Retatrutide (Eli Lilly, LY3437943) is an investigational triple hormone receptor agonist that activates the GIP, GLP-1 and glucagon receptors at once. In the Phase 2 trial it reached up to 24.2% mean weight reduction at 48 weeks (Jastreboff et al., NEJM 2023), the strongest effect reported for this drug class to date. It is not yet approved by the FDA or EMA and is offered exclusively as a research peptide (RUO).
What is retatrutide?
Retatrutide is an experimental once weekly peptide that simultaneously activates three metabolic hormone receptors, the first triple agonist of its kind in obesity and metabolic research. Its molecular mass is 4731.3 Da and a C20 fatty diacid modification gives it a half life of roughly six days, which supports once weekly dosing in trials.
Where earlier drugs targeted one or two receptors, retatrutide adds glucagon receptor activation to the GIP and GLP-1 mechanisms, and this third pathway is the main reason it is studied so intensively.
How does retatrutide work?
Retatrutide is a triple agonist: it activates the GIP receptor, the GLP-1 receptor and the glucagon receptor together. GLP-1 and GIP agonism reduce appetite and improve insulin response, while glucagon receptor activation is associated in research with increased energy expenditure and effects on liver fat metabolism. Combining all three is the hypothesis behind its potency: the pathways are thought to add up rather than overlap.
This is the same logic that separates it from dual agonists such as tirzepatide, which we cover in the retatrutide vs tirzepatide comparison.
Retatrutide trial results
In the Phase 2 trial (Jastreboff et al., NEJM 2023, PubMed 37366315), retatrutide at 12 mg produced a mean weight reduction of up to 24.2% at 48 weeks, with most participants losing 5% or more of their initial body weight. The Phase 3 TRIUMPH program has reported figures around 28% over longer treatment, the strongest weight effect published for an incretin based compound so far.
Trials also reported improvements in secondary cardiometabolic markers including blood pressure, HbA1c and blood lipids, and notable reductions in liver fat in participants with fatty liver (NAFLD). These are trial outcomes, not guaranteed results.
Retatrutide vs tirzepatide (quick view)
Retatrutide is a triple agonist (GIP/GLP-1/glucagon); tirzepatide is a dual agonist (GIP/GLP-1). Retatrutide showed greater weight reduction in trials, but tirzepatide is already approved while retatrutide is not. In trials retatrutide reached up to 24.2% at 48 weeks against 20.9% for tirzepatide in SURMOUNT-1, but these are separate programmes with different populations, so the comparison is indicative rather than direct.
| Criterion | Retatrutide | Tirzepatide |
|---|---|---|
| Receptors | GIP + GLP-1 + glucagon | GIP + GLP-1 |
| Trial weight reduction | up to 24.2% (Ph 2) / ~28% (Ph 3) | up to 20.9% (SURMOUNT) |
| Half-life | ~6 days | ~5 days |
| Approval | investigational | approved (Mounjaro/Zepbound) |
For the full breakdown see the dedicated retatrutide vs tirzepatide article.
Half-life and dosing in trials
Retatrutide is given once weekly by subcutaneous injection in trials, supported by its roughly six day half life. Trial protocols use stepwise titration, with each dose step held for at least four weeks to reach steady state and manage tolerability, up to a maximum studied dose of 12 mg. These figures describe trial design for research context only and are not a dosing recommendation.
Side effects reported in trials
The most common side effects in retatrutide trials are gastrointestinal: nausea, diarrhoea, vomiting, constipation and reduced appetite, typically mild to moderate, dose dependent and improving over time. Transient increases in heart rate were also recorded. No new “unusual” adverse effects beyond those common to the GLP-1 drug class were reported in the published trials, but long term safety continues to be evaluated in Phase 3.
Legal status and where retatrutide fits
Retatrutide is investigational: it is in Phase 3 and is not approved by the FDA or EMA, with regulatory approval not expected before 2027 to 2028. At Molequa® it is available strictly for laboratory research. If your protocol requires a reference grade compound, our retatrutide research peptide is HPLC/MS tested with batch documentation and EU shipping. It is supplied as research use only (RUO) and is not intended for human or animal consumption.
FAQ
What is retatrutide? An investigational once weekly triple agonist (GIP/GLP-1/glucagon) studied for body weight and metabolic parameters.
How strong is retatrutide in trials? Up to 24.2% mean weight reduction at 48 weeks in Phase 2, with roughly 28% reported in Phase 3.
Is retatrutide approved? No, it is investigational and not approved by the FDA or EMA.
How is retatrutide different from tirzepatide? Retatrutide adds glucagon receptor activation to GIP and GLP-1, making it a triple rather than dual agonist.
Where can I buy retatrutide for research? Molequa® supplies retatrutide as a research peptide (RUO) with HPLC/MS testing and EU delivery.
Legal notice: Retatrutide is offered exclusively for scientific laboratory research (RUO). It is not intended for human or animal consumption. This article summarises published research data and is not medical advice.
