Side-by-side · Research reference
GLP-1 (7-37)vsHumanin
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticHUMAN-REVIEWED16/43 cited
BAnimal-StrongHUMAN-REVIEWED14/52 cited
GLP-1 (7-37)
Incretin Hormone · Native Peptide
Research use only · IV/SC in experimental settings
Humanin
Mitochondrial-Derived Peptide · Cytoprotective
SQ · Experimental
01Mechanism of Action
Parameter
GLP-1 (7-37)
Humanin
Primary target
GLP-1 receptor (class B GPCR)Koole 2015
Pathway
GLP-1R activation → cAMP production → PKA signaling → insulin secretion (pancreatic β-cells)Lu 2025Koole 2015
Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival
Downstream effect
Glucose-dependent insulin release, glucagon suppression, delayed gastric emptying, reduced food intakeLu 2025Ding 2017
Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022Lue 2021Velentza 2024
Feedback intact?
Yes — physiological secretion and degradation preserved
Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis
Origin
Endogenous peptide cleaved from proglucagon in intestinal L cells; secreted postprandially
Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022Shahzaib 2026
Antibody development
—
Not reported in animal models
02Dosage Protocols
Parameter
GLP-1 (7-37)
Humanin
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.
—
Standard experimental dose (HNG)
—
4 mg/kg IP (rat)
Most common dose in rodent models.
Ex vivo bone culture
—
1 µg/mL
Protective against venetoclax-induced bone growth retardation.
Frequency
—
Daily (IP)
Duration
—
8–12 weeks in animal studies
Human data
—
None — no clinical trials reported
Analog (HNG)
—
Gly[14]-humanin — more potent variant
Substitution at position 14 enhances cytoprotective activity.
03Metabolic / Fat Loss Evidence
Parameter
GLP-1 (7-37)
Humanin
Mechanism
GLP-1R activation in hypothalamic satiety centers (arcuate nucleus) reduces food intakeLu 2025
Effect demonstrated with long-acting analogues (liraglutide).Lu 2025
—
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
—
Direct fat loss evidence
—
None
Mechanism overlap
—
Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect
04Side Effects & Safety
Parameter
GLP-1 (7-37)
Humanin
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
—
Animal model safety
—
Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks
Human safety data
—
None — no clinical trials
Theoretical fibrillation risk
—
Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.
Injection site reaction
—
Not reported in animal studies (IP route)
Reproductive safety
—
Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025
Absolute Contraindications
GLP-1 (7-37)
—Humanin
- ·Unknown — no human data
Relative Contraindications
GLP-1 (7-37)
—Humanin
- ·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)
05Administration Protocol
Parameter
GLP-1 (7-37)
Humanin
1. Research use only
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.
Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.
2. Storage
Lyophilised peptide stored at -20°C or below. Reconstituted solutions should be prepared fresh and used immediately due to rapid degradation.
Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.
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).
Daily administration in animal studies. Optimal timing not characterized.
4. Storage
—
Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.
5. Human use
—
No FDA approval, no IND, no clinical trials. Experimental research tool only.
06Stack Synergy
GLP-1 (7-37)
— no documented stacks
Humanin
+ MOTS-c
Multi-pathwayBoth are mitochondrial-derived peptides. MOTS-c enhances metabolic efficiency and insulin sensitivity via AMPK activation, while humanin prevents mitochondrial apoptosis. Combined, they address mitochondrial function (MOTS-c) and survival signaling (humanin), supporting cellular resilience under metabolic and oxidative stress.
- Humanin
- 4 mg/kg IP · daily (animal model)
- MOTS-c
- 5 mg/kg IP · daily (animal model)
- Frequency
- Once daily
- Primary benefit
- Mitochondrial health, metabolic efficiency, anti-apoptotic signaling