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Retatrutide

Metabolic

Also known as LY3437943, Reta

Triple agonist at the GIP, GLP-1 and glucagon receptors. Investigational.

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No approved label exists. Storage, stability after reconstitution and vial strength are undocumented for this compound, nothing sold as research material has verified identity, purity or sterility.

How it works

A single acylated peptide that activates three receptors at once. GLP-1 and GIP agonism suppress appetite and slow gastric emptying; adding glucagon receptor agonism raises energy expenditure, which is what separates it from the dual agonists.

Subcutaneous

In the body

Half-life
6 days
Time to peak
30 h
90% gone after
19.9 d
Builds up to
1.8×
Steady state after about 30.4 d at once weekly.
Aug 3Aug 6Aug 9Aug 12Aug 15Aug 18Aug 2112:09 PM

Shape of a single dose, modelled as one compartment with first-order absorption. The peak is normalised to 100% because bioavailability and volume of distribution are not published for most of these compounds.

Roughly 6 days, from the phase 1b multiple-ascending-dose study.

What happens, and when

  1. 0 min, 12 hAbsorbing from the injection site. Little felt yet.
  2. 12 h, 2 dPeak plasma levels. Appetite suppression and any nausea are usually strongest here.
  3. 2 d, 6 dPast peak, still around half of the peak level. Steady appetite effect.
  4. 6 d, 14 dFalling toward trough. Appetite often returns late in the week.

Doses

1 mg, 12 mgonce weeklyClinical trial

Range of maintenance doses studied in the phase 2 obesity trial.

Phase 2 escalation to 12 mg

NCT04881760 (phase 2 obesity), 2 mg starting arm · 48 weeks total

  1. wk 1, 42 mg4 weeks
  2. wk 5, 84 mg4 weeks
  3. wk 9, 128 mg4 weeks
  4. wk 13, 4812 mgMaintenance through week 48.

The dose sequence is verified from the trial registry. The four-week step length is the interval widely reported for this trial but could not be confirmed from the registry or the paper, so treat the timing as approximate.

Phase 2 escalation to 8 mg

NCT04881760, 2 mg starting arm · 48 weeks total

  1. wk 1, 42 mg4 weeks
  2. wk 5, 84 mg4 weeks
  3. wk 9, 488 mg40 weeks

Phase 1b rapid escalation

NCT04143802, cohort 5 · 12 weeks total

  1. wk 1, 23 mg2 weeks
  2. wk 3, 46 mg2 weeks
  3. wk 5, 89 mg4 weeks
  4. wk 9, 1212 mg4 weeks

Step lengths here are verified from the paper: two weeks, two weeks, then four and four.

Side effects

  • Nausea, vomiting, diarrhoea and constipation, all dose-related
  • Eructation, which showed up specifically at the highest doses
  • Heart rate rose 2 to 13 bpm at 24 hours post-dose in the three highest dose groups
  • Decreased appetite to the point of inadequate intake

Cautions

  • Not an approved medicine anywhere. There is no label, no established safety monitoring and no verified source of supply.
  • Trial exclusion criteria included personal or family history of medullary thyroid carcinoma and MEN 2, following the class warning on other incretin drugs.

Status

Investigational. Not approved by the FDA or any other regulator. Phase 3 (TRIUMPH) doses are blinded and not public.

Sources

Reference information for personal record-keeping. Not medical advice, and not a recommendation to use any of these compounds.