Retatrutide
Eli Lilly's investigational 'triple agonist.' Phase 2 results were striking, and the Phase 3 TRIUMPH program is underway.
Quick chart
Change these and every table below updates.
Dosing schedules (as studied)
Both schedules come from groups in the 48-week Phase 2 trial, with step-ups every 4 weeks. Each group then stayed at its target dose for the rest of the trial.
Gradual start
Lower-start groupsStarts at 2 mg and steps up every 4 weeks. Trial groups on this path stopped at 4 mg, 8 mg or 12 mg. The full path to 12 mg is shown.
| Phase | Weeks | Weekly dose | Syringe units | Volume | Doses per vial* |
|---|---|---|---|---|---|
| Start | 1–4 | 2 mg | 13.3 | 0.133 mL | 4 |
| Step 2 | 5–8 | 4 mg | 26.7 | 0.267 mL | 4 |
| Step 3 | 9–12 | 8 mg | 53.3 | 0.533 mL | 3 |
| Target | 13–48 | 12 mg | 80 | 0.8 mL | 2 |
* Limited by the vial's contents or the 28-day use limit after mixing, whichever comes first.
The trial found that starting at 2 mg rather than 4 mg partly reduced stomach side effects.
- 22 × 30 mg vials (each vial is used for at most 28 days after mixing)
- 44 mL bacteriostatic water (2 mL per vial)
- 48 × 1 mL (100-unit) U-100 insulin syringes
- 118 alcohol prep pads, plus a sharps container
Faster start
Higher-start groupsStarts at 4 mg and steps up once, reaching 8 mg at week 5. This was the quickest escalation the trial tested.
| Phase | Weeks | Weekly dose | Syringe units | Volume | Doses per vial* |
|---|---|---|---|---|---|
| Start | 1–4 | 4 mg | 26.7 | 0.267 mL | 4 |
| Target | 5–48 | 8 mg | 53.3 | 0.533 mL | 3 |
* Limited by the vial's contents or the 28-day use limit after mixing, whichever comes first.
This group reached its target sooner but had more gastrointestinal side effects than the 2 mg start.
- 16 × 30 mg vials (each vial is used for at most 28 days after mixing)
- 32 mL bacteriostatic water (2 mL per vial)
- 48 × 1 mL (100-unit) U-100 insulin syringes
- 112 alcohol prep pads, plus a sharps container
Reconstitution for this setup
- Let the 30 mg vial reach room temperature and wipe both stoppers with alcohol.
- Slowly add 2 mL of bacteriostatic water, aiming down the inside wall of the vial.
- Swirl gently until clear. Never shake.
- Label the vial: 15 mg/mL, with today's date. Refrigerate and use within 28 days.
Trial results by group
| Trial group | Starting dose | Target dose | Weight change at 48 weeks |
|---|---|---|---|
| 1 mg | 1 mg | 1 mg | −8.7% |
| 4 mg (low start) | 2 mg | 4 mg | −17.1% (both 4 mg groups) |
| 4 mg | 4 mg | 4 mg | |
| 8 mg (low start) | 2 mg | 8 mg | −22.8% (both 8 mg groups) |
| 8 mg | 4 mg | 8 mg | |
| 12 mg | 2 mg | 12 mg | −24.2% |
| Placebo | — | — | −2.1% |
- Side effects were mostly gastrointestinal and dose-related. Starting at 2 mg rather than 4 mg partly reduced them.
- Heart rate rose with dose, peaking at 24 weeks and declining afterward.
- Retatrutide is investigational. These are doses studied under medical supervision, not an approved regimen.
Research summary
Retatrutide adds glucagon-receptor activity to the GIP and GLP-1 approach used by tirzepatide. The idea is to increase energy expenditure as well as reduce appetite.
What the research shows
- In a 48-week Phase 2 trial (NEJM, 2023), the highest dose group lost an average of about 24% of body weight.
- Lilly's Phase 3 TRIUMPH trials are studying obesity, knee osteoarthritis, sleep apnea and cardiovascular outcomes. Check Lilly's announcements for the latest readouts.
- Side effects in trials were mainly gastrointestinal, along with dose-related increases in heart rate.
References
- Jastreboff AM, et al. Triple–hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med 2023. View source
- ClinicalTrials.gov NCT04881760: arm descriptions and dose-escalation paths for the Phase 2 trial. View source
- ClinicalTrials.gov NCT05882045: Phase 3 TRIUMPH trial of retatrutide. View source
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Last reviewed: November 2026