Starting protocol · Retatrutide

Split Dose Protocol: Dosage Chart for Twice-Weekly Injection

Divide your weekly retatrutide dose across 2 injections to reduce peak drug concentration by an estimated 30–40% — smoother levels, fewer GI spikes, same total weekly exposure.

Who Is This Protocol For?

Split Dose Dosage Chart

Week Weekly Total Split As Example Days Notes
1–20.5 mg0.25 mg × 2Wed / SunUltra-conservative start
3–41.0 mg0.5 mg × 2Wed / SunAppetite suppression begins
5–82.0 mg1.0 mg × 2Wed / SunTherapeutic threshold
9–124.0 mg2.0 mg × 2Wed / SunFull effect; evaluate at 12 wk
13+6.0 mg3.0 mg × 2Wed / SunOnly if plateau detected

Reta dosing chart: each step lasts at least 4 weeks. Weekly totals match the conservative protocol — only the delivery pattern changes.

How Splitting Reduces Side Effects

30–40% estimated Cmax reduction vs single weekly injection
injections per week — same total dose
~6 days half-life — makes splitting pharmacokinetically viable

With a ~6-day half-life, splitting a weekly dose into two injections 3–4 days apart produces lower peak concentration (each injection is half the dose), more stable trough levels (less "valley" on days 5–7), and essentially the same total weekly drug exposure. You're not using less drug — just distributing it more evenly.

The TRT analogy

This is the same principle used in testosterone replacement therapy, where splitting weekly injections into twice-weekly reduces estradiol spikes and improves hormonal stability. For retatrutide, the benefit is a smoother GLP-1/GIP/glucagon activation curve with fewer acute GI events on injection day.

Choosing Injection Days

The ideal split puts 3–4 days between injections:

Pattern Days Between
Monday / Thursday3 and 4 days
Tuesday / Friday3 and 4 days
Wednesday / Sunday4 and 3 days
Monday / Friday4 and 3 days

Retadose supports arbitrary injection-day selection. Set your dose days in Settings and the PK model computes your concentration curve using the actual timing of each injection.

How to Take a Split Dose

Each reta injection is subcutaneous — under the skin, same technique as once-weekly. The only difference: you inject twice per week at half the dosage each time. Use separate injection sites for each dose (e.g., left abdomen Wednesday, right abdomen Sunday). Consistent timing matters most — set reminders for both dose days.

Switching from Single to Split Dosing

  1. Wait until your next scheduled injection day
  2. Inject half your current weekly dose
  3. 3–4 days later, inject the other half
  4. Continue on the split pattern going forward

No washout period is needed. The total weekly dose stays the same — only the delivery pattern changes. Your PK curve in Retadose will update automatically when you log the split doses.

Companion Requirements

When split dosing may not help

Split dosing reduces peak-related side effects. It does not help with sustained nausea lasting 3+ days (a total-dose problem), appetite suppression that's too strong (same AUC regardless of split), or injection site reactions (more injection events may worsen site discomfort).

Track Your Split Doses with Retadose

Retadose models split doses natively — each injection is logged independently and the PK engine computes overlapping decay curves. See the flatter concentration profile that split dosing produces compared to single weekly injection.

Start the split dose protocol →

References

  1. Jastreboff AM et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." N Engl J Med 2023; 389:514–526. DOI: 10.1056/NEJMoa2301972.
  2. Coskun T et al. "LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist." Cell Metabolism 2022; 34(11). DOI: 10.1016/j.cmet.2022.09.014.
  3. TRIUMPH-4 Phase 3 trial protocol. ClinicalTrials.gov NCT05929066.