Retatrutide Dosing & Titration: The Complete Protocol Guide

Dosing Overview

Retatrutide is administered as a once-weekly subcutaneous injection, similar to semaglutide and tirzepatide. The titration is gradual to minimize GI side effects.

Phase 3 (TRIUMPH-1) Titration Schedule

The Phase 3 protocol uses a 4-week-per-step escalation:

Weeks	Dose	Notes
1-4	2 mg	Starting dose
5-8	4 mg	First escalation
9-12	6 mg	Intermediate
13-16	8 mg	Intermediate
17-20	10 mg	Near-target
21+	12 mg	Maintenance (highest dose)

Total ramp-up time: 20 weeks to reach full maintenance dose.

Phase 2 Titration Schedule (Research Protocol)

The earlier Phase 2 trial used a different escalation:

Weeks	Dose
1-4	0.5 mg
5-8	1 mg
9-12	2 mg
13-16	4 mg
17-24	8 mg
25+	12 mg

This slower ramp gave researchers more safety data at each level.

Dose-Response Relationship

The TRIUMPH-1 data shows clear dose-dependent results:

• 4 mg maintenance: 19% body weight loss — comparable to tirzepatide
• 9 mg maintenance: 26% loss — exceeds any approved drug
• 12 mg maintenance: 28-30% loss — unprecedented in clinical trials

The jump from 4mg to 9mg provides the biggest incremental benefit. Going from 9mg to 12mg adds another 2-3 percentage points.

Side Effects by Dose Level

Side effects are dose-dependent and most common during titration:

2-4 mg (weeks 1-8): Mild nausea in ~15%, usually resolves within a few days of each increase.

6-8 mg (weeks 9-16): Nausea peaks here for most people. Appetite suppression becomes very noticeable. Some report reduced energy temporarily.

10-12 mg (weeks 17+): GI side effects typically stabilize. Strong appetite suppression. Some users report increased body heat (likely from the glucagon-mediated metabolic increase).

How It Differs from Semaglutide/Tirzepatide Dosing

• Faster titration — reaches maintenance in 20 weeks vs 16-20 for tirzepatide
• Fewer dose steps — larger jumps between levels
• Higher absolute doses — 12mg vs 2.4mg semaglutide or 15mg tirzepatide (not directly comparable due to different potencies)
• More pronounced thermogenic effect — the glucagon component means some users feel warmer, especially after meals

Injection Details

• Volume: Similar to tirzepatide — approximately 0.5 mL per injection at maintenance
• Sites: Abdomen, thigh, or upper arm (rotate weekly)
• Day of week: Any day, keep consistent
• Storage: Refrigerated (2-8°C), likely in pre-filled pen format if approved

Who Might Be Prescribed Retatrutide

Based on the trial inclusion criteria, likely candidates once approved:

• BMI ≥30 (obesity) OR BMI ≥27 with weight-related comorbidity
• Adults who have plateaued on current GLP-1 medications
• Patients with significant MASH/fatty liver disease (trials show dramatic liver fat reduction)

Current Status

Retatrutide is NOT yet approved or commercially available. The Phase 3 TRIUMPH program includes multiple trials. FDA submission is expected 2026-2027, with potential approval in 2027-2028.