What Is Retatrutide's Half-Life?
A drug's elimination half-life (t½) is the time for plasma concentration to fall 50% after the peak following a single dose. For retatrutide, Coskun et al. (2022) measured t½ across therapeutic dose levels:
| Dose | Mean Half-Life |
|---|---|
| 0.5 mg | ~144 hours (6.0 days) |
| 1.5 mg | ~156 hours (6.5 days) |
| 4.5 mg | ~165 hours (6.9 days) |
| 9 mg | ~162 hours (6.75 days) |
Source: Coskun T et al. Cell Metabolism 2022. Half-life is approximately dose-independent across the therapeutic range — a key property for predictable PK modeling.
How Retatrutide Half-Life Compares to Other Weekly Injectables
| Drug | Half-Life | Steady State |
|---|---|---|
| Semaglutide (Ozempic / Wegovy) | ~7 days (168 h) | ~5 weeks |
| Retatrutide (LY3437943) | ~6 days (144–165 h) | ~4–5 weeks |
| Tirzepatide (Mounjaro / Zepbound) | ~5 days (120 h) | ~4 weeks |
| Dulaglutide (Trulicity) | ~5 days | ~4 weeks |
Dose Stacking: What the 6-Day Half-Life Means for Weekly Dosing
At a 168-hour injection interval (once weekly) and a 6-day half-life, approximately 53–60% of the prior dose remains when the next injection is given. After several weeks on a stable dose, the total drug exposure reaches plateau:
| Week | Approx. Level (as multiple of single injection) |
|---|---|
| After week 1 | 1.0× |
| After week 2 | ~1.6× |
| After week 3 | ~2.1× |
| After week 4 | ~2.5× |
| Steady state (weeks 5+) | ~3.0–3.5× |
This is the stacking phenomenon. Your "dose" is not the injection amount — your effective drug exposure at steady state is three or more times the injection amount. Escalating to a new dose at week 4 adds the new, higher dose on top of 2.5× the old dose, which is why peak concentrations spike during escalation windows before settling.
How Long Does Retatrutide Stay in Your System?
Approximately five half-lives are needed for a drug to be effectively cleared (~97% eliminated). For retatrutide:
- 1 half-life (~6 days): 50% remains
- 2 half-lives (~12 days): 25% remains
- 3 half-lives (~18 days): 12.5% remains
- 4 half-lives (~24 days): ~6% remains
- 5 half-lives (~30 days): ~3% remains — effectively cleared
Skipping one injection and waiting a full week before the next reduces your level by only about 13% compared to having injected on schedule. The 6-day half-life means even a two-week gap drops the level by only ~50–60%. This is not a reset — returning at the same dose will re-accumulate to prior steady state over weeks 4–5.
Clinical Significance of the Half-Life for Dosing
The dose-independent half-life across the therapeutic range means the stacking math is consistent and predictable — which is what makes pharmacokinetic modeling practically useful. If the half-life varied widely with dose, a simple model would be unreliable. Because it does not, a one-compartment model calibrated to the Coskun et al. (2022) PK constants can produce reliable level estimates from injection history alone.
This is the foundation of what Retadose computes: an estimated retatrutide concentration curve derived from your injection log, using the published PK constants.