Published-trial titration record
Retatrutide: published trial titration schedule
Retatrutide is not MHRA-licensed and is supplied for laboratory research only. The doses below describe the schedule used in the Jastreboff et al. Phase 2 trial (NEJM 2023) — they are not protocols for human use. Phase 3 TRIUMPH-1 has retained the same titration framework but the registrational dose schedule may differ at marketing authorisation.
Trial anchor
Jastreboff et al. Phase 2 trial (NEJM 2023, PMID 37366315, DOI 10.1056/NEJMoa2301972).
Full molecule profile: Retatrutide
Published titration schedule (trial record)
| Step | Trial-arm dose | Notes |
|---|---|---|
| Week 1-2 | 2 mg weekly | Phase 2 starting dose. |
| Week 3-4 | 4 mg weekly | First therapeutic step in the 4 mg arm. |
| Week 5-8 | 8 mg weekly (target for 8 mg arm) | Higher doses jump every 2 weeks. |
| Week 9-12 | 12 mg weekly (highest tested dose) | Continued through week 48. ~24% mean weight reduction. |
Maintenance phase (as reported)
Phase 2 maintained 12 mg weekly through 48 weeks. Phase 3 TRIUMPH-1 has not published its final maintenance schedule but Eli Lilly disclosures suggest 12 mg remains the targeted maintenance dose.
Route & storage (trial protocol)
Subcutaneous in the Phase 2 trial. Storage protocols for research-grade material follow standard peptide handling: lyophilised at -20°C; reconstituted material at 2-8°C, used within 4-6 weeks.
Missed-dose handling (trial protocol)
Phase 2 protocol allowed a single missed dose to be administered up to 48 hours late; beyond 48 hours, the dose was skipped and the next dose was the next scheduled administration.
Methodological considerations
- Resting heart rate increase of 3-6 bpm observed at higher doses in Phase 2 — under continued investigation in Phase 3.
- Modest reductions in HDL-cholesterol seen at the 12 mg dose; longer-term implications pending.
- Glycaemic control in T2DM with concomitant glucagon-receptor agonism is the central open question — TRIUMPH-2 will address.
- Not approved for human use in the UK — for laboratory and analytical research only.
What this evidence does not prove
- · A published titration arm is not a prescription, recommendation or self-administration guide.
- · Trial-arm doses apply only within the studied population, comparator, duration and primary endpoint.
- · Individual suitability requires qualified clinical assessment where licensed; investigational compounds require authorised research oversight.
- · Off-label, compounded, grey-market or self-supplied versions of the same active ingredient may have substantially different identity, purity, sterility and pharmacokinetics.
FAQs
- Why are retatrutide weekly doses much smaller than tirzepatide?
- Receptor agonist potency on each individual receptor (GLP-1, GIP, glucagon) differs from tirzepatide's GIP/GLP-1 profile, and the molecular design optimises for triple binding rather than maximum single-receptor potency. The result is that effective doses in milligrams are lower for retatrutide than for tirzepatide despite producing larger weight reductions.
- Is retatrutide available privately in the UK?
- No. Retatrutide is not a licensed medicine. It is not legal to supply to patients. Research-grade material exists for laboratory use only and is not interchangeable with a registered pharmaceutical product.
- How long until retatrutide is approved?
- MHRA marketing authorisation typically follows 12-18 months after the pivotal Phase 3 readout. With TRIUMPH-1 expected to read out in H1 2026, the earliest realistic UK licensing window is late 2027 or 2028. SURMOUNT-MMO and SURPASS-CVOT analogues (CV-outcomes trials for retatrutide) would land later still.