Retatrutide
Retatrutide is an investigational injectable peptide designed to activate the GLP-1, GIP and glucagon receptors at once, which has now reported results from its first phase 3 obesity trial.
Regulatory status: Investigational. Phase 3 results from TRIUMPH-1 were reported in 2026, but retatrutide has no FDA or other regulatory approval and no approved label.
Default vial
10 mg
Default mix
2 mL
Reported range
4–12 mg (phase 3 arms)
Draw (U-100)
40 u
Investigational — no approved dose exists. Phase 3 TRIUMPH-1 randomised 4, 9 and 12 mg once weekly, every arm starting at 2 mg and escalating over 16 weeks. The earlier phase 2 trial used 1, 4, 8 and 12 mg; 8 mg is not a phase 3 dose.
Where these numbers come from
Phase 3 TRIUMPH-1 randomised 4, 9 and 12 mg once weekly. Every arm starts at 2 mg and steps up every four weeks across a 16-week escalation period before holding a maintenance dose; the 4 mg arm reaches its dose in a single step. The phase 2 ladder (2 → 4 → 8 → 12 mg) is historical — 8 mg is not a phase 3 dose. Investigational — no approved dose exists.
Dose ladder: Phase 3 escalation to the 12 mg arm: 2 mg → 4 → 6 → 9 → 12 mg in 4-week steps (16 weeks of escalation, then maintenance)
- Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity — TRIUMPH-1, NEJM 2026
- Rationale and design of the TRIUMPH registrational trials, Diabetes Obes Metab 2026 (16-week escalation, 4/9/12 mg arms)
- Jastreboff et al., Triple-Hormone-Receptor Agonist Retatrutide for Obesity — Phase 2, NEJM 2023 (historical)
Reviewed October 2026
What it is
- A triple hormone receptor agonist targeting GLP-1, GIP and glucagon receptors.
- An engineered single peptide, structurally related to the GIP/GLP-1 peptide scaffolds.
- Given once weekly by subcutaneous injection. The phase 3 trials randomised maintenance doses of 4, 9 and 12 mg.
- Subcutaneous, investigational use only.
How it is described to act
- 1
Administered subcutaneously in trial settings, on a weekly schedule like related incretin peptides.
- 2
Reported to reach tissues bearing GLP-1, GIP and glucagon receptors, including liver, adipose tissue, pancreas and central feeding centres.
- 3
Proposed to act across three receptor systems at once, with the glucagon component hypothesised to add an energy-expenditure effect beyond appetite suppression.
- 4
In the phase 3 cohort this was associated with substantial weight reduction over 80 weeks, with effects reported to track the assigned dose.
What the research has looked at
Phase 3 obesity trial (TRIUMPH-1)
- TRIUMPH-1 randomised 2,339 adults with obesity 1:1:1:1 to weekly retatrutide 4, 9 or 12 mg or placebo, treating for 80 weeks.
- Every arm started at 2 mg and stepped up every four weeks across a 16-week escalation period before holding its maintenance dose; per the trial design paper the 4 mg arm reached its dose in a single up-titration.
- Lilly reported mean weight reductions of 19.0%, 25.9% and 28.3% for the 4, 9 and 12 mg arms against roughly 2.2% on placebo in its on-treatment analysis; analyses counting everyone who started give lower figures, and the sponsor and press reports differ on the exact percentages.
- Lilly reported that 45.3% of participants on 12 mg reached a weight reduction of 30% or more.
Phase 2 obesity trial (historical)
- The earlier phase 2 trial (NEJM, 2023) tested 1, 4, 8 and 12 mg once weekly, escalating every four weeks from a 2 mg or 4 mg start.
- Jastreboff et al. reported substantial mean weight reduction at the 12 mg dose over 48 weeks compared with placebo, and noted weight loss had not plateaued by week 48 in the higher-dose groups.
- The phase 2 authors suggested that refining the escalation scheme for phase 3 might improve the side-effect profile. The phase 3 arms are 4, 9 and 12 mg — 8 mg was a phase 2 dose and is not used in phase 3.
Strength of evidence: Limited human evidence
Phase 3 randomised results have been reported for obesity, but retatrutide remains unapproved and the full trial programme, including cardiovascular outcomes, is not complete.
Some human data exist, but they are small, short, or not designed to answer the questions people ask online.
Reported cautions and unknowns
- Nausea, diarrhoea, vomiting and constipation were the most common adverse events in the trials, mostly during dose escalation.
- In TRIUMPH-1, Lilly reported discontinuation for adverse events in 4.1%, 6.9% and 11.3% of the 4, 9 and 12 mg arms against 4.9% on placebo — that is, dropout rose with dose.
- Lilly also reported dysesthesia (abnormal skin sensation) in 5.1%, 12.3% and 12.5% of those arms against 0.9% on placebo.
- Investigators in the phase 2 trial observed heart-rate increases, which the authors attributed to the glucagon-receptor component.
- Long-term pancreatitis, gallbladder, thyroid and pregnancy safety data are not established because the trial programme is incomplete.
References
- 1.Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1), NEJM (2026)
- 2.Rationale and design of the TRIUMPH registrational clinical trials, Diabetes Obes Metab (2026)
- 3.Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial, NEJM (2023)
- 4.Lilly — TRIUMPH-1 topline results announcement (21 May 2026)
Handling this vial
- Lyophilized vials are generally stored at 2–8 °C and kept out of light; once reconstituted with bacteriostatic water they are refrigerated and commonly discarded after 28 days.
- Mix by aiming water down the vial wall and rolling gently — do not shake — and never re-freeze a reconstituted vial.
- Pep-Tidy cannot verify what is in your vial. Ask your supplier for a current Certificate of Analysis (HPLC/MS).
Retatrutide questions people ask
How do you reconstitute Retatrutide?
A common starting point for a 10 mg vial of Retatrutide is 2 mL of bacteriostatic water, which gives 5 mg per mL. Aim the water down the inside wall of the vial, let it dissolve on its own, and roll gently instead of shaking. Pep-Tidy's reconstitution calculator will recalculate the numbers for any other vial size or water volume you use.
How many units of Retatrutide is one dose?
At 5 mg per mL, that works out to about 40 units on a U-100 insulin syringe for a 2000 mcg dose. Change the vial size, water volume, or target dose in the calculator and the syringe reading updates with it. This is arithmetic, not a dosing recommendation.
What dosing schedule is reported for Retatrutide?
Published and community sources describe 4–12 mg (phase 3 arms), subcutaneous, once weekly, typically run 24 weeks on. These figures describe what has been reported, not what anyone should take — talk to a licensed clinician first.
How should Retatrutide be stored?
Lyophilized Retatrutide vials are generally kept at 2–8 °C and out of light. Once reconstituted with bacteriostatic water they are refrigerated and commonly discarded after about 28 days. Never re-freeze a reconstituted vial and never shake it.
Read this before you act on anything above
Everything on this page is a summary of what other people have published — it is not medical advice, not a recommendation, and not a dosing instruction. Reported dose ranges describe what appears in the literature or in community protocols, not what anyone should take. Talk to a licensed clinician before using any peptide.