Side-by-side · Research reference
DihexavsGLP-1 (7-37)
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED7/28 cited
BHuman-MechanisticHUMAN-REVIEWED16/43 cited
Dihexa
Angiotensin IV Analogue · Pre-Clinical
Not established — animal studies only
GLP-1 (7-37)
Incretin Hormone · Native Peptide
Research use only · IV/SC in experimental settings
01Mechanism of Action
Parameter
Dihexa
GLP-1 (7-37)
Pathway
HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization
GLP-1R activation → cAMP production → PKA signaling → insulin secretion (pancreatic β-cells)Lu 2025Koole 2015
Downstream effect
Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models
Feedback intact?
—
Yes — physiological secretion and degradation preserved
Origin
Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015
Endogenous peptide cleaved from proglucagon in intestinal L cells; secreted postprandially
Antibody development
—
—
02Dosage Protocols
Parameter
Dihexa
GLP-1 (7-37)
Human dosing
Not established — no human trials
—
Animal studies
Mouse/rat models only — dosing not translatable to humans
—
Evidence basis
Pre-clinical / Rodent models
—
Clinical status
No Phase 1, 2, or 3 trials published
—
Clinical use
—
None — native GLP-1 not used therapeutically
Engineered analogues (semaglutide, liraglutide) used clinically.Friedman 2024
Research dosing
—
Variable — 0.1–10 nmol/kg in animal models
Used as reference standard for analogue comparison.
Modified analogues
—
t½ extended to 13 h (liraglutide), 165 h (semaglutide)
Via DPP-4 resistance + fatty acid acylation.
03Metabolic / Fat Loss Evidence
Parameter
Dihexa
GLP-1 (7-37)
Mechanism
—
Native GLP-1 efficacy
—
Minimal — rapid degradation prevents sustained appetite suppression
Gastric emptying
—
Delayed in animal models, contributing to satiety
Body weight impact
—
Not observed with native GLP-1 — requires analogue formulations
04Side Effects & Safety
Parameter
Dihexa
GLP-1 (7-37)
Human safety data
None available — no human clinical trials
—
Theoretical c-Met risks
c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile
—
Pre-clinical tolerability
Not systematically reported in available studies
—
Native GLP-1
—
Well-tolerated in research settings; no prolonged exposure data
Hypoglycemia risk
—
Low — insulin secretion is glucose-dependent
Analogue side effects
—
Nausea, vomiting, diarrhea (GLP-1R agonists)
Not applicable to native GLP-1 due to non-therapeutic use.
GLP-1 resistance
—
High glucose-induced PKCβ overexpression may reduce GLP-1 responsiveness in endothelial cellsPujadas 2016
Absolute Contraindications
Dihexa
- ·Not approved for human use — research compound only
GLP-1 (7-37)
—Relative Contraindications
Dihexa
- ·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)
GLP-1 (7-37)
—05Administration Protocol
Parameter
Dihexa
GLP-1 (7-37)
1. Human administration
No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.
Native GLP-1(7-37) is not formulated for therapeutic use. Administered IV or SC in experimental protocols to study GLP-1R pharmacology and as reference standard for analogue development.
2. Legal status
Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.
Lyophilised peptide stored at -20°C or below. Reconstituted solutions should be prepared fresh and used immediately due to rapid degradation.
3. Clinical alternatives
—
For therapeutic GLP-1R activation, use FDA-approved long-acting analogues: semaglutide (once weekly), liraglutide (once daily), dulaglutide (once weekly), or exenatide (twice daily or once weekly).