How it works
Retatrutide (Eli Lilly code LY3437943) is a single peptide that activates three receptors at once: GIP, GLP-1 and glucagon. The glucagon component is what separates it from the single (GLP-1) and dual (GIP and GLP-1) agonists that came before it. In the phase 1b trial its half-life was approximately 6 days with dose-proportional exposure, which is why every trial gives it once a week.
The dose is the lever. In the 48-week phase 2 obesity trial, weight fell 8.7% at 1 mg and 24.2% at 12 mg; in the liver substudy, liver fat fell 42.9% at 1 mg and 82.4% at 12 mg at 24 weeks. What follows is every dose the trials used, what it produced, and how it was reached.
What the trials showed
The human dose range of retatrutide was mapped in three steps: a 12-week phase 1b multiple-ascending-dose study, two 36 to 48-week phase 2 trials, and a phase 3 program that began in 2023. The table lists every weekly maintenance dose that has been published with results, and the starting dose that led to it.
Two things stand out. First, no trial has gone above 12 mg a week, so 12 mg is the ceiling of the human evidence. Second, the phase 3 designers dropped 1 mg and 8 mg and inserted 9 mg, a choice the Lancet authors say was informed by the phase 2 dose-response data.
| Trial | Weekly dose | Escalation | Weeks | Reported result |
|---|---|---|---|---|
| Phase 2 obesity, NEJM 2023 | 1 mg | no escalation | 48 | -8.7% body weight |
| Phase 2 obesity, NEJM 2023 | 4 mg | 2 or 4 mg start | 48 | -17.1% body weight |
| Phase 2 obesity, NEJM 2023 | 8 mg | 2, 4 then 8 mg (or 4 then 8) | 48 | -22.8% body weight |
| Phase 2 obesity, NEJM 2023 | 12 mg | 2, 4, 8 then 12 mg by week 12 | 48 | -24.2% body weight |
| Phase 2 obesity, NEJM 2023 | Placebo | none | 48 | -2.1% body weight |
| Phase 2 type 2 diabetes, Lancet 2023 | 0.5 mg | fixed | 36 | HbA1c -0.43 pts; weight -3.19% |
| Phase 2 type 2 diabetes, Lancet 2023 | 4 mg | 2 mg start, or none | 36 | HbA1c -1.39 / -1.30 pts; weight -7.92% / -10.37% |
| Phase 2 type 2 diabetes, Lancet 2023 | 8 mg | slow (2, 4, 8) or fast (4, 8) | 36 | HbA1c -1.99 / -1.88 pts; weight -16.81% / -16.34% |
| Phase 2 type 2 diabetes, Lancet 2023 | 12 mg | 2, 4, 8 then 12 mg | 36 | HbA1c -2.02 pts; weight -16.94% |
| Phase 3 TRANSCEND-T2D-1, Lancet 2026 | 4 mg | per protocol | 40 | HbA1c -1.69 pts; weight -11.5% |
| Phase 3 TRANSCEND-T2D-1, Lancet 2026 | 9 mg | per protocol | 40 | HbA1c -1.86 pts; weight -13.9% |
| Phase 3 TRANSCEND-T2D-1, Lancet 2026 | 12 mg | per protocol | 40 | HbA1c -1.94 pts; weight -15.3% |
| Phase 3 TRIUMPH-1 and 2 (registry) | 4, 9, 12 mg | 16-week fixed escalation | 80 | not yet published |
| Phase 3 TRIUMPH-3 and 4 (registry) | 9, 12 mg | 16-week fixed escalation | 80 | not yet published (68 wk in TRIUMPH-4) |
Table 1. Every retatrutide trial arm with a published human result, plus the completed phase 3 arms awaiting publication. Weight figures are least-squares mean changes at the end of treatment; HbA1c at 24 weeks (phase 2) or 40 weeks (phase 3). Sources: Jastreboff et al., NEJM 2023 (338 adults); Rosenstock et al., Lancet 2023 (281); Bajaj et al., Lancet 2026 (537); TRIUMPH registry entries. DOIs in the Sources section.
Weight change by dose: 8.7% at 1 mg, 24.2% at 12 mg
The clearest dose-response data comes from the NEJM phase 2 obesity trial. Participants had a BMI of 30 or higher, or 27 to 30 with a weight-related condition, and were followed for 48 weeks. The chart shows the least-squares mean percentage change in body weight at the primary endpoint (24 weeks) and at the end of treatment (48 weeks).
Figure 2
In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.
The curve flattens at the top. Going from 1 mg to 4 mg roughly doubled the effect, 4 mg to 8 mg added another 5.7 points, and 8 mg to 12 mg added 1.4 points. Weight was still falling at week 48 in the higher dose groups, which is one reason the phase 3 trials run to week 80.
How the protocols climbed: 2, 4, 8, 12
Every maintenance dose above 1 mg was reached by steps, not in one jump. In the phase 2 obesity trial the registry describes the 12 mg arm as "2 mg starting dose followed by 4 mg, 8 mg and then 12 mg", with escalation "up to Week 12".
That is three steps in twelve weeks, and the same 2 to 4 to 8 pattern was used for the 8 mg arm. Two arms were deliberately started at 4 mg instead of 2 mg to test whether the gentler start mattered; it did, for gastrointestinal tolerability, though not for the final weight result.
The phase 3 TRIUMPH trials use a "fixed dose escalation regimen" that takes 16 weeks, followed by 64 weeks of maintenance. The design paper does not print the intermediate steps, so this site does not guess them. Both programs allow a permanent dose reduction when gastrointestinal events or poor oral intake do not settle. The full week-by-week layout is in the dosing schedule guide, and the tolerability findings in the titration guide.
Figure 3
Why 12 mg is the number everyone quotes, and what it hides
By the numbers, 12 mg. It produced the largest mean weight change and the largest share of participants crossing each threshold: at 48 weeks, 100% lost at least 5%, 93% lost at least 10% and 83% lost at least 15% of their body weight. The 8 mg group was close behind at 100%, 91% and 75%.
Figure 4
Whether the extra 1.4 points from 8 to 12 mg is worth the dose-related increase in gastrointestinal events is exactly the question the phase 3 program was built to answer with larger numbers, which is why 9 mg sits between them in TRIUMPH.
In the liver substudy, 8 mg and 12 mg were almost identical (liver fat down 81.4% and 82.4% at 24 weeks), and in the type 2 diabetes trial the 8 mg and 12 mg HbA1c results were within 0.03 points of each other. All of those figures, by dose and by trial, are collected in the results page.
No standard dose, but one consensus: 4, 9 and 12 mg
No. Retatrutide has no marketing authorisation, so there is no label and no approved dose. The closest thing to a consensus is the phase 3 choice of 4, 9 and 12 mg once weekly, because that is what Lilly and its investigators considered worth testing in more than 5,800 people.
The first phase 3 publication, the 40-week TRANSCEND-T2D-1 trial in the Lancet in June 2026, reported mean weight changes of -11.5% at 4 mg, -13.9% at 9 mg and -15.3% at 12 mg in adults with type 2 diabetes, alongside HbA1c reductions of 1.69 to 1.94 percentage points.
Any text that presents a "protocol" outside these ranges, or a dose adjusted to body weight, is not drawn from the trials: none of the published studies dosed by weight, and none went below 0.5 mg or above 12 mg.
Retatrutide dosage in type 2 diabetes
The diabetes trials used the same ladder with one extra rung at the bottom: 0.5 mg. In the 2023 Lancet phase 2 trial, HbA1c at 24 weeks fell by 0.43 points at 0.5 mg, 1.30 to 1.39 at 4 mg, 1.88 to 1.99 at 8 mg and 2.02 at 12 mg, versus 0.01 with placebo and 1.41 with dulaglutide 1.5 mg.
Body weight at 36 weeks fell 3.19% at 0.5 mg and 16.94% at 12 mg. The dose-by-dose detail, including the 2026 phase 3 numbers, is in the type 2 diabetes dose guide.
A vial label is not a dose
Research suppliers sell retatrutide as lyophilised powder in vials labelled 5 mg, 10 mg or 20 mg. That number is the total peptide in the vial, not a weekly dose. A 10 mg vial reconstituted with 2 mL of diluent gives 5 mg/mL, so 4 mg (a phase 3 dose) occupies 0.8 mL and 12 mg would need more than one vial.
The arithmetic, with a calculator, is in the reconstitution guide, and the mapping of vial sizes to trial doses in the vial-size guide. Suppliers who publish a certificate of analysis per batch make it possible to check that the label matches the contents; one such listing is at See it at OXpeptides (research use only).
Side effects
The NEJM paper describes the adverse events in one sentence worth quoting in substance: the most common events were gastrointestinal, they were dose-related, mostly mild to moderate, and partially mitigated by the 2 mg starting dose compared with 4 mg. Heart rate increased in a dose-dependent way, peaked at 24 weeks and declined afterwards.
The side-effect profile by dose, including the heart-rate data, is the subject of the sister site retatrutiderisk.com, in particular its side-effects article.
Approval status
Retatrutide is an investigational compound. It has not been approved by the FDA, the EMA or any other regulator for any use, so there is no label and no approved dose. The phase 3 program (TRIUMPH-1 to 4, TRANSCEND-T2D) tests 4, 9 and 12 mg once weekly in more than 5,800 people; the first phase 3 paper, TRANSCEND-T2D-1, was published in The Lancet in 2026 and the obesity trials are registered with primary endpoints at week 80.
