The Dose Ledger
Retatrutide trial doses, read closely. An independent editorial project.
Pharmacokinetics

Retatrutide Half-Life: About 6 Days, and What It Means for Weekly Dosing

Updated 21 Sept 20267 min read4 sources
A glass hourglass with fine white sand next to a small glass specimen jar
~6 days
half-life, phase 1b (Lancet 2022)
45%
of a dose left after 7 days
4 to 5 wk
to reach steady state
<1%
of a dose left after 42 days

The phase 1b trial measured a half-life of approximately 6 days and dose-proportional exposure. That single number explains the once-weekly schedule, the slow climb to steady state, and why effects linger for weeks after the last dose.

The short version

  1. The phase 1b multiple-ascending-dose trial reported that retatrutide pharmacokinetics were dose proportional and its half-life was approximately 6 days.
  2. With a 6-day half-life and weekly dosing, steady state is reached after roughly 4 to 5 half-lives, about 4 to 5 weeks, which matches the 4-week steps used in the phase 2 escalation.
  3. At steady state the weekly trough is about 45% of the peak, so exposure never falls to zero between injections; after the last dose, under 1% remains at 42 days.
  4. In the phase 1 single-dose study a reduction in body weight persisted up to day 43 after one injection, in line with the slow clearance.

The measured number: approximately 6 days

The half-life of retatrutide comes from one primary source, the phase 1b multiple-ascending-dose trial published in The Lancet in 2022 (Urva and colleagues). Seventy-two adults with type 2 diabetes received weekly doses for 12 weeks in groups of 0.5, 1.5, 3, 3 then 6, and 3 then 6 then 9 then 12 mg.

The abstract states: "The pharmacokinetics of LY3437943 were dose proportional and its half-life was approximately 6 days." The earlier single-ascending-dose study in Cell Metabolism reached the same conclusion in different words, describing a pharmacokinetic profile that "supported once-weekly dosing".

"Dose proportional" is the second half of the finding and deserves equal weight: doubling the dose doubled the exposure across the range tested. That linearity is what lets the trial dose ladder (2, 4, 8, 12 mg) be read as a ladder of exposure too.

What does a 6-day half-life mean?

A half-life is the time for the amount of drug in the body to fall by half once absorption is complete. Six days is long for a peptide: unmodified GLP-1 has a half-life of a few minutes.

Retatrutide, like tirzepatide and semaglutide, carries a fatty-acid side chain that binds it to albumin in the blood, which shields it from enzymes and kidney filtration. The design goal is a molecule that can be injected once a week and still have a meaningful level in circulation on day seven.

Simple version

Half of the drug is gone every six days. That is slow enough that one injection a week keeps a steady level.

The decay curve

The chart draws the textbook first-order decay for a 6-day half-life. It is an illustration of the shape, not a measured plasma curve: real concentrations also depend on absorption from the injection site over the first days, and on individual variation.

Fraction of a single retatrutide dose remaining over 42 days, assuming a 6-day half-lifeExponential decay curve: 100 percent at day 0, 50 percent at day 6, 25 percent at day 12, 12.5 percent at day 18, 6.25 percent at day 24, about 3 percent at day 30, about 1.6 percent at day 36 and under 1 percent at day 42. Illustration of the approximately 6-day half-life reported by Urva et al., Lancet 2022.Fraction of one dose remaining, 6-day half-life (illustration)0%25%50%75%100%day 0day 650%day 1225%day 1812.5%day 246.3%day 30day 36day 42
A textbook first-order decay drawn with the approximately 6-day half-life reported in the phase 1b trial (Urva et al., Lancet 2022). Real plasma curves depend on absorption and on the individual; this is the shape, not a measurement.
A sand hourglass on a white windowsill in morning sun
A sand hourglass on a white windowsill in morning sun. Editorial photograph.

Time to steady state

With weekly dosing, each new dose lands on the roughly 45% of the previous one that is still present. The total climbs and then levels off when the amount eliminated each week equals the amount injected. That balance point, steady state, arrives after about 4 to 5 half-lives regardless of the dose: 24 to 30 days, or four to five weekly injections. At two weeks the level is about 80% of its eventual plateau; at four weeks about 96%.

This is the pharmacokinetic reason behind the trial schedules. The phase 2 registry states escalation was completed by week 12 through three steps for the 12 mg arm, which is a step every 4 weeks, and the phase 3 program uses 16 weeks. Each step waits for the previous level to reach its plateau, so that tolerability at that exposure can be judged before the next increase. The schedules themselves are in the dosing schedule guide.

Simple version

After any dose change it takes about a month for the level in the blood to settle. That is why the trials waited four weeks between steps.

Peak-to-trough within each week

Seven days is a little more than one half-life, so by the time the next injection is due about 45% of the post-dose level remains (0.5 raised to the power 7/6). The ratio of peak to trough is therefore about 2.2 to 1. That is a modest swing for a weekly drug, and it explains why the published trials never split the dose across the week: there was no pharmacokinetic need to.

The same arithmetic describes any gap in exposure. Fourteen days after an injection the level is about 20% of the post-dose peak, not zero; the trials do not publish a rule for interrupted dosing, and this site does not invent one. The figures here describe the shape of the curve, nothing more.

Washout after the last dose

Elimination is symmetrical with accumulation. After the final injection, 50% remains at day 6, 25% at day 12, 12.5% at day 18, 6.25% at day 24, about 3% at day 30 and under 1% at day 42. The trials build in a 4-week safety follow-up after the last dose, which covers about 94% of the washout.

The Cell Metabolism single-dose study found a body-weight reduction persisting up to day 43 after one injection, so the biological effect outlasts the presence of most of the drug. What weight does after that, once the compound is gone, has not been published for retatrutide; the question is taken up in the cycle length guide.

Why the half-life matters for reading the doses

Every dose figure on this site is a weekly dose, and the half-life is the reason a weekly dose is a meaningful unit. It also sets the interpretation of the 12 mg ceiling: at steady state the body carries not 12 mg but the accumulated total of the last several injections, which is why exposure-response modelling, not just the nominal dose, guided the phase 3 selection described in the TRIUMPH design paper.

The dose table and results live on the retatrutide dosage guide; how vial contents translate to those doses is in the reconstitution guide.

Questions readers ask

What is the half-life of retatrutide?

Approximately 6 days, as reported in the phase 1b multiple-ascending-dose trial in The Lancet (2022), with dose-proportional pharmacokinetics across the doses tested.

How long does retatrutide remain in the body after a dose?

Using first-order elimination with a 6-day half-life: 50% remains at 6 days, 25% at 12, 12.5% at 18, about 6% at 24, about 3% at 30 and under 1% at 42 days after the last dose.

How long does retatrutide take to reach steady state?

About 4 to 5 half-lives, so 24 to 30 days of weekly dosing at a constant dose. Each dose increase in the trials restarts that climb, which is why escalation steps were spaced 4 weeks apart.

Is retatrutide's half-life the same as tirzepatide's?

Both are in the same range of several days, which is what allows once-weekly dosing for both. This site only quotes the retatrutide figure, approximately 6 days, from its own phase 1b publication.

Sources

Reviewed against the primary sources on 21 Sep 2026. Every DOI resolves on CrossRef and every NCT number on ClinicalTrials.gov.

  1. Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet. 2022;400(10366):1869-1881. doi.org/10.1016/S0140-6736(22)02033-5
  2. Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism. 2022;34(9):1234-1247. doi.org/10.1016/j.cmet.2022.07.013
  3. Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine. 2023;389(6):514-526. doi.org/10.1056/NEJMoa2301972
  4. Giblin A, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Diabetes, Obesity and Metabolism. 2025;28:83-93. doi.org/10.1111/dom.70209

Back to the retatrutide dosage guide