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Trial protocolFat loss and metabolism

Retatrutide escalation, the phase 2 schema behind TRIUMPH-1

Weight loss with an investigational triple receptor agonist

The schedule a registered trial actually ran, taken from the paper and the trial registration rather than from a label summary. Every one carries a PubMed or ClinicalTrials record you can open.

Not advice. This is a record of a schedule, not a dose for you.

The schedule, as reported

Each field below is what the source states, not a rounded version of it. Where the source does not publish a detail, the field says so instead of filling the gap.

Amount
1 mg, 4 mg, 8 mg or 12 mg at maintenance, from a starting dose of either 2 mg or 4 mg
Frequency
Once weekly
Route
Subcutaneous injection
Duration
48 weeks in the phase 2 trial. The phase 3 TRIUMPH-1 ran 80 weeks with a further 24 week extension.

How it was reached, step by step

  1. 01

    Randomised 2:1:1:1:1:2:2 to one of six retatrutide arms or placebo

  2. 02

    The arms were 1 mg, 4 mg from a 2 mg start, 4 mg from a 4 mg start, 8 mg from a 2 mg start, 8 mg from a 4 mg start, and 12 mg from a 2 mg start

  3. 03

    Once weekly subcutaneous dosing for 48 weeks

  4. 04

    The published report does not give the week by week step timings, so they are not written here

What was measured

Percentage change in body weight from baseline to 24 weeks, primary. Percentage change at 48 weeks and the proportions reaching 5, 10 and 15 percent reductions were secondary. Safety, gastrointestinal events and heart rate were assessed.

What was reported

Results as the trial reported them, with their comparators.

  • At 24 weeks the least squares mean weight change was -7.2 percent on 1 mg, -12.9 percent on the combined 4 mg arms, -17.3 percent on the combined 8 mg arms and -17.5 percent on 12 mg, against -1.6 percent on placebo.

  • At 48 weeks it was -8.7 percent, -17.1 percent, -22.8 percent and -24.2 percent against -2.1 percent on placebo.

  • At 48 weeks a reduction of at least 15 percent had occurred in 60 percent of the 4 mg group, 75 percent of the 8 mg group and 83 percent of the 12 mg group, against 2 percent on placebo.

  • Gastrointestinal adverse events were dose related, mostly mild to moderate, and were partially reduced by starting at 2 mg rather than 4 mg. This is the reason the starting dose was itself randomised.

  • Heart rate rose in a dose dependent way, peaked at 24 weeks and declined afterwards.

Where this comes from

Jastreboff et al., Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial, New England Journal of Medicine, 2023. 338 adults, funded by Eli Lilly.

The phase 3 TRIUMPH-1 registration labels its arms Dose 1, Dose 2 and Dose 3 without publishing the milligram amounts, so the only retatrutide dosing schema on public record with amounts attached is the phase 2 one written above. Anyone quoting a phase 3 retatrutide dose is quoting something the registry does not state.

What this protocol cannot tell you

Required on every entry in this registry, and never empty.

Retatrutide is not approved anywhere, for anything. Every milligram figure above comes from a 338 person phase 2 whose primary endpoint was 24 weeks, and phase 2 doses are chosen to find the range rather than to be correct. The registry does not publish the phase 3 arm doses, so nobody outside Lilly can say what the trial that reported 28.3 percent actually gave. Heart rate rose with dose. Material sold as retatrutide is not made by the sponsor and nothing verifies its identity or content.

The compounds in this protocol

Each profile carries the full evidence record, the legal status and what the trials did not show.

  • Retatrutide

    An investigational once-weekly triple receptor agonist producing the largest pharmacological weight loss reported to date in trials.

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