Starting protocol · Retatrutide

Standard Starting Protocol: Dosage Schedule from TRIUMPH-4 Phase 3 Trial

The TRIUMPH-4 escalation protocol starting at 2 mg/week — the fastest path to therapeutic levels with the most published safety and efficacy data behind it.

Who Is This Protocol For?

Standard Dosage Chart (TRIUMPH-4)

Week Weekly Dose Frequency What to Expect
1–42.0 mg1× weeklyAppetite suppression begins; nausea common weeks 1–3
5–84.0 mg1× weeklySignificant appetite control; GI events typically improve
9–126.0 mg1× weeklyMost users' effective range; evaluate weight trajectory
13–169.0 mg1× weeklyOnly if 6 mg plateau; expect increased side effects
17+12.0 mg1× weeklyMaximum trial dose; ~20% dropout rate at this level

Reta dosing chart: source is TRIUMPH-4 Phase 3 trial protocol. Each step is 4 weeks — the minimum for retatrutide to approach steady state (based on ~6-day half-life).

Phase 2 Efficacy Data by Dose

24.2% weight loss at 12 mg / 48 weeks
22.8% at 8 mg — similar efficacy, fewer side effects
17.1% at 4 mg — already clinically significant

Jastreboff et al. (2023, N=338, 48 weeks) showed diminishing returns above 8 mg — the 12 mg arm added only 1.4 percentage points of weight loss with meaningfully higher GI adverse events. Many practitioners target 6–8 mg as the maintenance dose.

Why 2 mg Is the Starting Dose

The Phase 2 trial compared starting at 2 mg vs 4 mg when escalating to the same final dose. Starting at 2 mg produced lower nausea rates, comparable weight loss at 48 weeks, and better participant retention.

At steady state, 2 mg/week produces total drug exposure of approximately 3.7 mg equivalent — enough for measurable appetite suppression in most individuals while keeping GI burden manageable.

Dose stacking — what 2 mg really means

With a ~6-day half-life, ~54% of each dose is still active when the next injection is given. After 4 weeks on 2 mg/week, your total drug exposure is roughly 3.7 mg — not 2 mg. This accumulation is exactly why escalation must wait for steady state, and why doubling the dose feels like more than a doubling of effect.

How to Take This Protocol

Reta is injected subcutaneously once per week, on the same day each week. Pick a day that works for your schedule — consistency matters more than which day you choose. Common injection sites: abdomen (2 inches from navel), outer thigh, or upper arm. Rotate sites weekly. If you experience injection-day nausea, try evening dosing.

Companion Requirements

Exit Strategy

Phase Duration Action
Pre-taper2 weeksIncrease calories by 200–300/day before last full dose
Taper 12 weeksReduce to 50% of working dose
Taper 22 weeksReduce to 25% of working dose
Post-taperOngoingMaintain calorie + training habits; expect hunger rebound
Never stop abruptly

BMJ data suggests 4 kg/month regain without a structured exit protocol. Weight typically returns fully within 1.7 years of cessation without habit maintenance. The taper is non-negotiable.

Track Your Standard Protocol with Retadose

Log your injections and see your estimated drug concentration curve — know exactly when you've reached steady state at each dose level and whether escalation timing makes sense for your individual PK profile.

Start the standard 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.
  4. Wilding JPH et al. "Weight regain and cardiometabolic effects after withdrawal of semaglutide." Diabetes, Obesity and Metabolism 2022.