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Metabolic

Retatrutide Protocol

Dosing & Research

Last Updated: September 4, 2026

Chemical Identity
Molecular Formula
C221H342N46O68
Molecular Weight
4731.42 g/mol
CAS Number
2381089-83-2

Obesity and diabetes trials, Triple incretin pharmacology, Weight-loss studies, Cardiometabolic disease research

Evidence Level
Human Clinical Data Available
Species Studied
Human • Rat • Mouse
Half-Life
~6 Days
Administration
Subcutaneous
Frequency
Once Or Twice Weekly, Same Day Each Week

How It Works

  • Obesity and diabetes trials
  • Triple incretin pharmacology
  • Weight-loss studies
  • Cardiometabolic disease research

Dosing Structure

Dose
0.5–2.0 mg weekly
Frequency
Once Or Twice Weekly, Same Day Each Week
Notes
1x Weekly titration: Week 1-4: 2mg | Week 5-8: 4mg | Week 9-12: 6mg | Week 13-16: 8mg | Week 17+: 8-12mg. 2x Weekly titration: Week 1-4: 1mg | Week 5-8: 2mg | Week 9-12: 3mg | Week 13-16: 4mg | Week 17+: 4-6mg. *First-time GLP-1 users should consider starting at 1mg per week. No need to increase dose if experiencing benefits. Inject: Abdomen, thigh, upper arm (rotate weekly). Any time of day, same day each week. Typically follows a weekly titration schedule.

Example Protocols

Dose: 0.5–2.0 mg weekly
Frequency: Once Or Twice Weekly, Same Day Each Week
Duration: 8-48 weeks
Off Period: Not listed
Calculate dosing →

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Protocol Notes

1x Weekly titration
Week 1-4: 2mgWeek 5-8: 4mgWeek 9-12: 6mgWeek 13-16: 8mgWeek 17+: 8-12mg
2x Weekly titration
Week 1-4: 1mgWeek 5-8: 2mgWeek 9-12: 3mgWeek 13-16: 4mgWeek 17+: 4-6mg
•
*First-time GLP-1 users should consider starting at 1mg per week.
•
No need to increase dose if experiencing benefits.
•
Inject: Abdomen, thigh, upper arm (rotate weekly).
•
Any time of day, same day each week.
•
Typically follows a weekly titration schedule.

What Is Retatrutide?

Retatrutide is an investigational once-weekly injectable that activates three hormone receptors simultaneously - GLP-1, GIP, and glucagon - making it the first triple incretin agonist to enter advanced clinical trials. Its Phase 2 results showed the highest percentage weight loss ever recorded for a pharmaceutical compound in a randomized controlled trial.

Research Observations - Not Medical Claims
  • ▸Phase 2 weight loss trial (NEJM, 2023; PMID: 37351564): 338 adults with obesity received retatrutide for 48 weeks. The 24 mg dose group achieved a mean body weight reduction of 24.2% - the highest ever reported for a pharmaceutical in an RCT at that time.
  • ▸Dose escalation: The 12 mg dose produced 17.5% weight loss and the 4 mg dose 8.7%, demonstrating clear dose-response.
  • ▸Liver fat: Retatrutide significantly reduced liver fat fraction - mean reduction of ~82% in the highest dose group among participants with metabolic-associated fatty liver.
  • ▸Glucagon receptor contribution: The addition of glucagon agonism increases energy expenditure compared to GLP-1 alone, contributing to the enhanced weight loss beyond what tirzepatide achieves.
  • ▸Cardiometabolic markers: Significant improvements in triglycerides (−45%), blood pressure, and waist circumference observed in Phase 2.

Evidence Summary

Human Clinical Data AvailableInvestigational - Phase 3 clinical trials ongoing (Eli Lilly); not yet approved by FDA or EMA
Evidence StrengthStrong
PreliminaryModerateStrong
Curated Citations3
Largest Study (n)338
Most Recent Study2024
Species Studied
HumanRatMouse

Commonly Researched With

Tirzepatide
Head-to-head comparison context - both dual/triple incretin agonists studied for metabolic disease; not combined.
Semaglutide
GLP-1 class benchmark - researchers compare retatrutide outcomes against semaglutide as the established standard.
NAD+
NAD+ restoration and incretin agonism are both studied in metabolic longevity research for complementary mechanisms.

Research & Studies

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