What Is Retatrutide? Dosage, Half-Life & How to Track It
Also known as: LY3437943 · Triple-G agonist · Reta
Retatrutide is an investigational triple agonist — it activates GIP, GLP-1, and glucagon receptors at once — and produced up to 24% body-weight loss at 48 weeks in Phase 2 trials, more than either semaglutide or tirzepatide at comparable doses. Its ~6-day half-life supports once-weekly dosing, titrated slowly from 1 mg toward a 12 mg maximum over roughly five months. It is not yet FDA-approved; this is educational information, not medical advice.
What retatrutide is and how it works
Retatrutide (development code LY3437943) is the first triple-receptor agonist in the GLP-1 class, hitting GIP, GLP-1, and the glucagon receptor in a single molecule. Semaglutide activates one of those three; tirzepatide activates two.
The added glucagon-receptor activity is the differentiator. Where GLP-1 and GIP mainly suppress appetite and improve insulin sensitivity, glucagon signaling pushes the liver to burn fat for energy — a genuine thermogenic effect layered on top of eating less. That third pathway is the leading explanation for retatrutide’s edge in trial weight loss over dual and single agonists, and it’s also why it tends to raise resting heart rate more than they do.
The evidence is substantial for an investigational drug — Phase 2 data plus Phase 3 TRIUMPH topline results — but it’s still unapproved. Treat protocols below as trial-derived and community-adapted, not an approved label.
Typical dosing & titration
Trial dosing escalates far more slowly than semaglutide or tirzepatide, in part because the glucagon-receptor pathway is new territory even for people who have already run a GLP-1. The Phase 3 structure steps roughly every four weeks:
- Weeks 1–4: 1–2 mg
- Weeks 5–8: 2–4 mg
- Weeks 9–12: 4–6 mg
- Weeks 13–16: 6–9 mg
- Weeks 17–20: 9–12 mg (maximum studied dose)
| Vial | BAC water | Concentration | 1 unit (U-100) ≈ |
|---|---|---|---|
| 5 mg | 1 mL | 5 mg/mL | 50 mcg |
| 10 mg | 1 mL | 10 mg/mL | 100 mcg |
| 30 mg | 3 mL | 10 mg/mL | 100 mcg |
A 10 mg/mL concentration keeps every dose from 2 to 10 mg inside a single 1 mL syringe, which is why higher-mg vials are usually cut with more water rather than less. Doses above roughly 8 mg often need a second injection site — the calculator flags it when a volume exceeds 1 mL.
Half-life & what it means for frequency
Retatrutide’s half-life runs about 6 days, in the same range as tirzepatide. Steady state at any given dose takes roughly 4–5 half-lives — about four weeks — which is the whole reason the trial protocol holds each titration step for a month before allowing an increase: you can’t fairly judge a dose you haven’t reached steady state on yet.
The same math applies in reverse. After stopping, retatrutide takes about a month to fully clear. A short gap (a week or so) is fine to resume at the same dose; missing two or more weeks means restarting a rung lower, the same logic used with tirzepatide and semaglutide.
What to track & common side effects
Side effects follow the same GI pattern as other incretin drugs — nausea, diarrhea, vomiting, constipation — but run somewhat hotter at the top of the dose range, and retatrutide adds a heart-rate effect the others don’t: roughly 5–7 bpm average increase at the 12 mg dose, driven by the glucagon receptor.
Two things are worth tracking that don’t show up on a scale. Resting heart rate, since trial data flags it as dose-dependent and worth watching after each step-up. And, same as any GLP-class compound, protein intake and the loss rate — retatrutide’s stronger appetite suppression makes it easier to under-eat protein and lose weight faster than the 0.5–1%/week that best protects muscle.
How to track Retatrutide in Stackeddd
Log the weekly dose and which rung of the ladder you’re on — with a 4-week minimum per step, it’s easy to lose track of when you’re actually eligible to move up. Trend resting heart rate alongside weight so a real spike doesn’t get missed in the noise, and keep protein visible since retatrutide’s appetite suppression is strong enough to make undereating easy.
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Blood-Level Simulator
Model it yourself: pick retatrutide, set your weekly dose, and watch levels build toward the ~4-week steady state at each step — the same pharmacokinetic engine that runs inside the app.
Related compounds
Related reading: Semaglutide vs Tirzepatide: half-life, cadence, and what to track · Peptide reconstitution math: how much BAC water to add
Frequently asked questions
What is retatrutide used for?
It’s an investigational triple GIP/GLP-1/glucagon receptor agonist studied for obesity and type 2 diabetes. Phase 2 trials showed up to 24% body-weight loss at 48 weeks, and it is not yet FDA-approved.
What is the half-life of retatrutide?
About 6 days. Steady state at a given dose takes roughly 4–5 half-lives — around four weeks — which is why trial titration holds each dose step for a month before escalating.
How is retatrutide titrated?
Trial protocols step roughly every 4 weeks: 1–2 mg, then 2–4, 4–6, 6–9, up to a 9–12 mg maximum studied dose around week 20. Starting at 1–2 mg rather than higher meaningfully reduces early nausea.
Is retatrutide stronger than tirzepatide?
In trial data, yes on average — the added glucagon-receptor activity produces roughly 3–5% more weight loss than tirzepatide at comparable doses, though it also raises resting heart rate more. It remains investigational, unlike tirzepatide.
This is educational information, not medical advice. Doses and protocols above reflect published references and community practice — protocol decisions belong with your prescribing physician. Generic names used throughout. How this reference is built & how the AI is tested →
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