Metabolic

Retatrutide

Acylated peptide · GIP/GLP-1/glucagon triple agonist · Synthetic

FDA · PHASE 3 TRIALS

Half-life

~6.0 days

Long

minsdays

Route

SubQ injection

Evidence

Clinical trial data

Risk

Standard

Overview

Known for

Triple agonist (GLP-1/GIP/Glucagon). Most potent weight loss peptide currently available. Phase 3 trials showed average 28.7% body weight loss. Also being studied for NASH/fatty liver disease and sleep apnea.

Mechanism

Triple agonist — GIP + GLP-1 + glucagon receptors. Most potent weight loss peptide in trials. Glucagon component adds thermogenesis.

Key facts

Format
Lyophilized powder
Scientific name
LY3437943 · Acylated tri-agonist peptide (GLP-1 / GIP / glucagon receptor)
Mechanism targets
Classification
Active
Supply & nature
ExogenousExogenous
FDA category
Phase 3 trials

Evidence & standing

Evidence base
Clinical trial data
Risk level
Standard
Clinical phase
Phase 3
Best studies
4 references
  • Jastreboff et al. (2023) Phase 2 Trial. NEJM 389(6):514-526. DOI: 10.1056/NEJMoa2301972
  • Lilly TRIUMPH-4 Phase 3 (2025): 28.7% weight loss at 68wk, NCT05931367
  • Meta-analysis: PMC12026077 (2025) — 3 RCTs, 878 patients
  • NOT YET FDA APPROVED — Phase 3 program ongoing (7 trials, results expected 2026)

Dosage & protocol

Typical dose
0.5mg
Research range
1–12 mg
Cycle
Weekly injection
Onset
10 days first effects
Full effect
126 days
Half-life
~6d
~6 days (t½ ~136hrs)
Protocol

Titrate: 0.5mg → 1mg → 1.5mg → 2mg → 3mg → 4mg → 6mg weekly. Increase weekly or hold if sides are bad. Max ~8-12mg. SubQ once weekly.

Time to effects

EARLY: 1-2 weeks

FULL: 12-24 weeks

Week 1-2: Appetite suppression kicks in quickly. GI side effects (nausea, diarrhoea) are common early — this is the glucagon receptor activity.

Week 2-4: Measurable weight loss. Energy changes from glucagon receptor activation.

Week 4-8: Significant fat loss visible. Titration still progressing toward maintenance.

Week 12-24: Full effect at maintenance dose. Phase 3 trials showed ~28.7% body weight loss at 48 weeks. Liver fat reduction measurable by 24 weeks.

Minimum commitment: 12 weeks. Optimal: 24-48 weeks.

Recommended vial
  • 10mg vials

Standard titration (0.5→6mg) uses ~10mg over first 5-6 weeks ✓. Fits neatly within shelf life. At 6mg/wk maintenance, order more frequently.

Reference figures only

Dosing reflects published laboratory protocols and is not guidance for use in any living subject.

Safety

Reversibility
Unknown
Side effects

Nausea (23%), diarrhoea (22%), vomiting (11%), constipation (10%), ⚠️ dysesthesia/paraesthesia (20.9% at 12mg — NEW safety signal from TRIUMPH-4)

Interactions

Expected similar to tirzepatide: insulin, sulfonylureas, oral contraceptives. Glucagon component may affect hepatic drug metabolism.

Do not combine
CagrilintideCagrilintide Cagrilintide 5mg + Semaglutide 5mg (Blend)Cagrilintide 5mg + Semaglutide 5mg (Blend) SemaglutideSemaglutide SurvodutideSurvodutide TirzepatideTirzepatide

Handle with research caution

  • Do NOT combine with Tirzepatide, Semaglutide, or Survodutide (never stack GLP-1 agonists)
  • Do NOT combine with CagriSema (GLP-1 overlap)
  • Caution with insulin or sulfonylureas (hypoglycaemia risk)

Storage & handling

Lyophilised
12–24 months
2–8°C
Reconstituted
4–6 weeks
2–8°C

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