Side-by-side · Research reference

HexarelinvsVIP

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 1HUMAN-REVIEWED19/45 cited

BPhase 3HUMAN-REVIEWED9/42 cited

Hexarelin

Hexapeptide GHRP · Cardio-tropic

100–200 mcgPer doseSmith 1996

Phase 1Evidence levelGhigo 1997

~70 minHalf-lifeSemenistaya 2010

SQ · Multiple sites · 1–3×/day

VIP

Neuropeptide · VPAC1/VPAC2 Agonist · Emergency Use Authorization (COVID-19 ARDS)

IntravenousPrimary routeBrown 2023

ARDSLead indicationUdupa 2025

Phase 3Development stage

IV infusion · Inhaled (investigational)Brown 2023 Boesing 2022

01Mechanism of Action

Parameter

Hexarelin

VIP

Primary target

Ghrelin receptor (GHS-R1a) + cardiac CD36Smith 1996 Ghigo 1997

VPAC1 and VPAC2 G-protein-coupled receptorsUdupa 2025

Pathway

GHS-R1a → Gαq → Ca²⁺ → GH release. CD36 engagement → direct cardio-tropic actionGhigo 1997

VIP → VPAC1/VPAC2 activation → cAMP elevation → Pulmonary vasodilation + epithelial protection

Downstream effect

Strong GH pulse + IGF-1 elevation; cardio-protective effects in animal MI modelsGhigo 1997

Anti-inflammatory cytokine modulation, alveolar-capillary membrane stabilization, pulmonary smooth muscle relaxation, reduced neutrophil infiltration

Feedback intact?

Yes initially; tachyphylaxis with chronic useGhigo 1997

Yes — exogenous VIP acts as physiological agonist

Origin

Synthetic hexapeptide His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂Smith 1996

Endogenous 28-amino-acid neuropeptide; synthetic analogue (aviptadil) identical to natural VIP

Antibody development

—

02Dosage Protocols

Parameter

Hexarelin

VIP

Standard dose

100–200 mcg per injectionSmith 1996

—

Frequency

1–2× per day max (tachyphylaxis with chronic 3× daily)

—

Lower / starter dose

50 mcg per dose

—

Evidence basis

Phase 1 / Phase 2 trialsSmith 1996 Ghigo 1997

Phase 3 RCT (TESICO)Brown 2023

816-patient randomized controlled trial in COVID-19 ARDS.

Duration

4–8 weeks on / 4–8 weeks off (tachyphylaxis mitigation)

—

Reconstitution

Bacteriostatic water

Lyophilized powder reconstituted with sterile diluent per protocol

Timing

Pre-sleep + fasted preferred

—

Half-life

~70 minSemenistaya 2010

~2 minutes (plasma)

Rapid clearance necessitates continuous infusion.

Intravenous (ARDS protocol)

—

60–90 mcg/kg/day via continuous infusion

TESICO trial protocol for COVID-19 ARDS.

Infusion duration

—

12-hour continuous IV infusion dailyBrown 2023

Inhaled (investigational)

—

Variable dosing under clinical trial protocolsBoesing 2022

Delivered via nebulizer for direct pulmonary deposition.

Treatment duration

—

3–14 days (acute ARDS)

04Side Effects & Safety

Parameter

Hexarelin

VIP

Cortisol elevation

Modest at high dosesGhigo 1997

—

Prolactin elevation

Modest at high dosesGhigo 1997

—

Hunger

Strong appetite increase via ghrelin agonism

—

Tachyphylaxis

Receptor desensitisation with chronic dosingGhigo 1997

—

Cardiac effects

Direct cardio-tropic; potential benefit in MI but unstudied in humansGhigo 1997

—

IGF-1 elevation

Strong; monitor with chronic high-dose use

—

Cancer risk

Contraindicated in active malignancy (GH/IGF-1 axis)

—

Pregnancy / OB

Avoid

—

Hypotension

—

Transient vasodilation-related blood pressure drop

Tachycardia

—

Reflex tachycardia secondary to vasodilation

Infusion site reactions

—

Erythema, phlebitis (IV administration)

GI symptoms

—

Nausea, diarrhea (VIP is endogenous GI peptide)

Overall tolerability

—

Well-tolerated in Phase 3 trials; adverse event profile comparable to placebo

Absolute Contraindications

Hexarelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

VIP

·Known hypersensitivity to aviptadil or formulation components

Relative Contraindications

Hexarelin

·Untreated diabetes
·Severe hyperprolactinemia

VIP

·Severe hypotension or shock states (monitor blood pressure)
·Pregnancy — insufficient safety data

05Administration Protocol

Parameter

Hexarelin

VIP

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

Reconstitute lyophilized aviptadil powder with sterile diluent per manufacturer protocol. Inspect solution for particulates — should be clear and colorless.

2. Injection site

SQ — abdomen or thigh. Rotate sites.

Administer as continuous 12-hour intravenous infusion via central or peripheral line. Use infusion pump for precise dosing (60–90 mcg/kg/day divided over infusion duration).

3. Timing

Pre-sleep + fasted preferred. Cycle on/off to avoid tachyphylaxis.

Monitor blood pressure, heart rate, and oxygenation continuously during first infusion. Assess for hypotension and adjust infusion rate if needed.

4. Storage

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

Deliver via jet or mesh nebulizer per clinical trial protocol. Patient seated upright, normal tidal breathing for 10–15 minutes.

5. Needle

29–31G, 4–8 mm insulin syringe.

Store lyophilized powder at 2–8 °C, light-protected. Reconstituted solution: use immediately or within 24 hours if refrigerated.

06Stack Synergy

Hexarelin

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

Hexarelin (GHRP) + CJC-1295-no-DAC (GHRH analogue) is the higher-amplitude variant of the standard GHRH+GHRP stack. Hexarelin produces a stronger pulse than ipamorelin but with cortisol + prolactin signal — choose this stack for maximum GH amplitude when side-effect tolerance is acceptable. Cycle aggressively.

Hexarelin: 100 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: Maximum GH pulse amplitude (with side-effect signal)

Smith 1996 Teichman 2006

VIP

— no documented stacks