Side-by-side · Research reference
LL-37vsRetatrutide
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticHUMAN-REVIEWED15/35 cited
BPhase 2HUMAN-REVIEWED10/41 cited
LL-37
Cathelicidin · Human AMP
Broad-spectrumAntimicrobial activity
Endogenous · Secreted at inflammation sites
Retatrutide
Triple-receptor agonist · Phase 3
SQ · Abdomen · Once weekly
01Mechanism of Action
Parameter
LL-37
Retatrutide
Primary target
GLP-1R + GIPR + Glucagon receptor (triple agonism)Jastreboff 2023
Pathway
hCAP-18 precursor → Proteinase-3 cleavage → LL-37 release → Membrane insertion/disruption
Triple-receptor activation → ↑insulin (GLP-1+GIP), ↓gastric emptying, ↑lipid handling, ↑energy expenditure (glucagon component)Jastreboff 2023
Downstream effect
Membrane permeabilization, cytokine induction, autophagy, phagosome-lysosome fusion, chemotaxisAhmad 2026Zhang 2026
Maximal weight loss across class. Glucagon component drives lipolysis and energy expenditure beyond GLP-1+GIP aloneJastreboff 2023
Feedback intact?
—
—
Origin
Endogenous human cathelicidin (37-AA fragment, residues 134–170 of hCAP-18)
Synthetic peptide engineered for balanced affinity at three incretin / glucagon receptorsJastreboff 2023
Antibody development
—
—
02Dosage Protocols
Parameter
LL-37
Retatrutide
Endogenous expression
Constitutive in neutrophils, epithelial tissues
Upregulated during infection and inflammation.Pinheiro 2026
—
Exogenous (experimental)
Dose varies by study; antimalarial ~10–50 μM in vitro
No FDA-approved exogenous formulation.
—
Plasma levels (malaria)
Elevated in infected patients and miceHe 2026
Exogenous administration reduced parasitemia in murine models.He 2026
—
Evidence basis
In vitro, animal models, human observational
Phase 2 trial; Phase 3 ongoingJastreboff 2023
Frequency
—
Once weekly
Titration schedule
—
2 mg → 4 mg → 8 mg → 12 mg over 16 weeks
Duration
—
Indefinite for chronic indication (presumed)
Reconstitution
—
Investigational; not commercially available
Timing
—
Any time of day
Half-life
—
~6 days (estimated from class)
04Side Effects & Safety
Parameter
LL-37
Retatrutide
Cytotoxicity (high dose)
Membrane disruption in host cells at supraphysiological concentrations
—
Pro-inflammatory signaling
Can exacerbate inflammation in certain contexts (context-dependent)Pinheiro 2026
—
Theoretical cancer risk
Immunomodulatory roles in tumor microenvironment under investigation
—
Glucose handling
—
Glycemic improvement; rare hyperglycemia from glucagon component
Pancreatitis risk
—
Class warning
Thyroid C-cell tumours
—
Class warning (presumed)
Pregnancy / OB
—
Avoid (insufficient data)
Absolute Contraindications
LL-37
—Retatrutide
- ·MTC personal or family history (presumed class effect)
- ·Pregnancy / breastfeeding
Relative Contraindications
LL-37
- ·Active autoimmune disease (theoretical immune dysregulation)
Retatrutide
- ·Severe gastroparesis
- ·History of pancreatitis
- ·Severe cardiovascular disease (HR signal)
05Administration Protocol
Parameter
LL-37
Retatrutide
1. Natural secretion
LL-37 is constitutively expressed in neutrophils and epithelial cells, cleaved from hCAP-18 by proteinase-3 at sites of infection or inflammation.
Investigational peptide. Research vials reconstituted with bacteriostatic water per label.
2. Experimental formulations
Synthetic LL-37 and derivatives (e.g., SAMP-12aa) tested in vitro and animal models. Administered via topical, intraperitoneal, or intravenous routes in research settings.
SQ — abdomen, thigh, or upper arm. Rotate weekly.
3. Stability considerations
LL-37 is resistant to pepsin degradation at gastric pH. Synthetic short peptides designed to retain this stability while reducing toxicity.Lu 2026
Once weekly, same day.
4. Storage
—
Refrigerate 2–8 °C. Light-protected.
5. Needle
—
27–31G, 4–8 mm insulin syringe.