Retatrutide (LY3437943) is a once-weekly injectable GIP/GLP-1/glucagon triple agonist currently available through compounding pharmacies as an off-label preparation. It has no FDA-approved commercial form as of 2026. The primary dosing reference is the Phase 2 randomized controlled trial (Jastreboff et al. 2023, N=338, 48 weeks).
What Doses Does Retatrutide Come In?
Compounding pharmacies supply retatrutide as a multi-dose vial, typically at concentrations of 2–10 mg/mL for subcutaneous injection. Common prescribed injection amounts: 0.5 mg, 1 mg, 2 mg, 4 mg, 8 mg, and 12 mg per weekly injection.
The Phase 2 Trial Retatrutide Dosing Schedule
The clearest published escalation reference comes from the 12 mg arm of Jastreboff et al. (2023):
| Weeks | Dose | Cumulative weeks at dose |
|---|---|---|
| 1–4 | 2 mg | 4 weeks |
| 5–8 | 4 mg | 4 weeks |
| 9–12 | 8 mg | 4 weeks |
| 13+ | 12 mg | Maintenance |
Source: Jastreboff et al. (2023). The 8 mg and 4 mg arms used similar 4-week step intervals from a 2 mg or 4 mg starting dose. All arms used once-weekly subcutaneous injection.
The Half-Life Problem That Makes Retatrutide Dosing Non-Obvious
Retatrutide has a mean elimination half-life of approximately 6 days (144–165 hours) across therapeutic dose ranges, per Coskun et al. (2022). At once-weekly (168-hour) dosing intervals, this means:
- At injection #2: approximately 53–60% of injection #1 is still circulating
- At injection #3: residual from injections #1 and #2 both remain
- At steady state (weeks 4–5): total drug exposure stabilizes at roughly 3–4× the single-injection amount
Escalating the dose every 4 weeks means the new, higher dose stacks on top of residual levels from weeks 1–3. Peak drug concentration climbs steeply with each escalation before settling — which is why GI side effects cluster during escalation windows and typically improve as each new dose level reaches steady state.
Five half-lives is the standard pharmacokinetic rule for reaching approximate steady state (~97% of plateau). At a 6-day half-life, that's 30 days — roughly 4 weeks. The trial protocol escalated at 4 weeks because that's when most participants had roughly reached steady state at each level. It is the minimum safe escalation interval derived from the PK, not a clinically optimized window.
Retatrutide Dosing Schedule: Trial Protocol vs Adjusted Protocol
Many practitioners using compounded retatrutide apply longer intervals between dose steps than the trial protocol — 6 to 8 weeks per step — and hold escalation when GI symptoms are present.
The key principle: the goal is your therapeutic window — the sustained drug level at which appetite control is effective and side effects are acceptable. That window is individual. Some people achieve their response at 4 mg steady state; others need 8 mg or 12 mg. The standard protocol has no mechanism for identifying or holding you within your window; it simply escalates on schedule.
Starting Dose Considerations
The trial demonstrated that starting at 2 mg produced better tolerability than starting at 4 mg, with meaningfully lower nausea rates in participants escalating to the same final dose. Many practitioners now start compounded retatrutide at 0.5 mg or 1 mg — lower than any arm in the published trial — to minimize the dose-escalation GI burden while building up to an effective level.
The Phase 2 trial found 24.2% weight loss at 12 mg vs 22.8% at 8 mg — a 1.4 percentage point difference. The GI adverse event profile at 12 mg was meaningfully higher. Many practitioners target 8 mg as the maintenance dose for this reason.
Tracking Your Retatrutide Level During Dosing
Because each dose adds to prior residual drug, the total drug level at any timepoint is not just the last injection — it is the integral of all prior injections decaying at different rates. The Retadose app computes this using published PK parameters (Coskun et al. 2022) and your logged injection history, producing an estimated concentration curve that shows your level right now and how it will evolve through future injections.