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Retatrutide

Metabolic & Weight Loss

Retatrutide is a next-generation triple agonist peptide targeting GLP-1, GIP, and glucagon receptors, designed for potent weight loss and metabolic enhancement. It significantly improves body composition, glycemic control, and metabolic rate through synergistic mechanisms affecting appetite regulation, insulin sensitivity, and energy expenditure. Retatrutide is currently under clinical evaluation for obesity and type 2 diabetes management, demonstrating superior efficacy compared to GLP-1 monotherapies like Semaglutide or Tirzepatide. It is currently undergoing Phase II/III clinical trials for obesity and type 2 diabetes.

Reconstitute
2 mL BAC + 20mg vial
100 mcg/unit
Daily Range
2–12 mg Subcutaneous (SQ)
Once weekly
Standard Dose
4 mg
Cycle
4–8 weeks
then reassess
Retatrutidetriple agonistobesityGLP-1GIPglucagonfat lossweight management

Dosing & Reconstitution Guide

Clinical trials have tested weekly subcutaneous doses ranging from 4–12 mg. These are experimental protocols under FDA supervision

Standard / Gradual Approach

20mg Vialstandard
PhaseDoseVolume
Weeks 1–42,000 mcg (2 mg)20 units (0.20 mL)
Weeks 5–84,000 mcg (4 mg)40 units (0.40 mL)
Weeks 9–128,000 mcg (8 mg)80 units (0.80 mL)
Weeks 13+12,000 mcg (12 mg)120 units (1.20 mL) — split into 2 injections or use 2 vials

Standard / Gradual Approach

30mg Vialstandard
PhaseDoseVolume
Weeks 1–42,000 mcg (2 mg)20 units (0.20 mL)
Weeks 5–84,000 mcg (4 mg)40 units (0.40 mL)
Weeks 9–128,000 mcg (8 mg)80 units (0.80 mL)
Weeks 13+12,000 mcg (12 mg)120 units (1.20 mL) — split into 2 injections or use 2 vials

Standard / Gradual Approach

10mg Vialstandard
PhaseDoseVolume
Weeks 1–42,000 mcg (2 mg)40 units (0.40 mL)
Weeks 5–84,000 mcg (4 mg)80 units (0.80 mL)
Weeks 9–128,000 mcg (8 mg)160 units (1.60 mL) — use 2 vials or split injection
Weeks 13+12,000 mcg (12 mg)240 units (2.40 mL) — use 2 vials or split injection

Standard / Gradual Approach

5mg Vialstandard
PhaseDoseVolume
Weeks 1–42,000 mcg (2 mg)80 units (0.80 mL)
Weeks 5–84,000 mcg (4 mg)160 units (1.60 mL) — use 2 vials
Weeks 9–128,000 mcg (8 mg)320 units (3.20 mL) — use 2 vials
Weeks 13+12,000 mcg (12 mg)480 units (4.80 mL) — use 3 vials

Protocol Summary

Subcutaneous (SQ): Once weekly · Dose range 2–12 mg with gradual titration
Cycle Length: 4–8 weeks typical; reassess before extending

Frequency & Cycling

Subcutaneous

Retatrutide is dosed weekly, typically starting at 2 mg for the first 4 weeks, then increasing by 2 mg increments every 4 weeks up to 12 mg. Overlapping with other incretin-based therapies (like GLP-1 or GIP agonists) should be avoided unless supervised.

🧪 Quick Start

Vial Size
20 mg
BAC Water
2 mL
Concentration
10 mcg/unit
Starting Dose
2,000 mcg (2 mg) (20 units (0.20 mL))
Maintenance Dose
12,000 mcg (12 mg) (120 units (1.20 mL) — split into 2 injections or use 2 vials)

Potential Benefits & Use Cases

Retatrutide is a research compound in clinical development. It is not approved for medical use.
Achieves up to 24% body weight reduction at 48 weeks with 12 mg weekly dosing (Phase 3)
Reduces HbA1c by ~2.0% in adults with type 2 diabetes (Phase 3)
Reduces osteoarthritis knee pain by 75.8% (WOMAC score) with 14% achieving complete pain remission (human trial)
Reverts 72% of prediabetic participants to normoglycemia (Phase 3)
Improves lipid profiles — ~20% reduction in non-HDL cholesterol, significant triglyceride reduction (Phase 3)
Convenient once-weekly subcutaneous administration (Phase 3)
Clinical data Strong preclinical Limited data

Mechanism of Action

→GLP-1 receptor agonism (enhances insulin secretion, delays gastric emptying, reduces appetite)
→GIP receptor agonism (increases insulin sensitivity, suppresses appetite)
→Glucagon receptor agonism (enhances energy expenditure and fat oxidation)

Lifestyle & Optimization

timing

Weekly injection. Consistent timing.

diet

Protein-forward diet (1.0–1.2 g/kg) to preserve lean mass. Smaller, more frequent meals for GI management. Adequate hydration during titration.

exercise

Resistance training (2–3x weekly) and aerobic exercise.

sleep

Sleep 7–9 hours.

Peptide Research & Preclinical Studies

Evidence-Based Research Findings

Study TitleType
New England Journal of Medicine — Jastreboff AM et al. (2023) Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 TrialReference
The Lancet — Rosenstock J et al. (2023) Retatrutide, a GIP, GLP-1, and glucagon receptor agonist, for people with type 2 diabetesReference
ClinicalTrials.gov — NCT05929066: TRIUMPH Phase 3 trial of Retatrutide in obesityReference
Nature Reviews Drug Discovery — Triple agonist (GIP/GLP-1/glucagon) drugs for obesity and diabetesReference
Eli Lilly Press Release — Retatrutide Phase 2 results (up to 24.2% body weight reduction)Reference

Side Effects & Safety

Common Side Effects

• GI effects (nausea, diarrhea, vomiting) — mild-moderate, diminish over time
• Lower starting dose (2 mg vs 4 mg) reduces initial GI events

🧮 Dose Calculator

Concentration
100.0
mcg/unit
Draw Volume
5
units (0.050 mL)
For a 500 mcg dose, draw 5 units on a U-100 insulin syringe
🧬

Bioavailability & Absorption

SubQ Injection
High efficacy with once-weekly subcutaneous administration; sustained GLP-1, GIP, and glucagon receptor activation.
Oral Administration
No oral formulation currently available.
Half-Life
Estimated >6 days
Degradation
Primarily metabolized by proteolytic enzymes and renal clearance.
Tissue Specificity
Acts on pancreatic beta cells, central nervous system (appetite centers), liver, and adipose tissue.
⚗️

Peptide Details

Molecular Weight
4731.33
Formula
C223H343F3N46O70
Sequence
YA¹QGTFTSDYSIL²LDKK⁴AQA¹AFIEYLLEGGPSSGAPPPS³
⚖️

Legal Status & Regulatory

RegionStatus
FDANot Approved
EUNot Approved
AustraliaNot Approved
CanadaNot Approved

Storage Instructions

Lyophilized (Powder)
freeze at −20 °C (−4 °F); after reconstitution, refrigerate at 2–8 °C (35.6–46.4 °F) and use within 2–4 weeks
Reconstituted (Mixed)
Refrigerate at 2–8 °C (35.6–46.4 °F) immediately after mixing; use within 2–4 weeks for maximum potency