Side-by-side · Research reference

AOD-9604vsVIP

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

APhase 2HUMAN-REVIEWED10/47 cited

BPhase 3HUMAN-REVIEWED9/42 cited

AOD-9604

HGH 176-191 · β3-AR Lipolytic

250–300 mcgDaily doseHeffernan 2001

Phase 2Evidence levelHeffernan 2001 Ng 2000

~30 minHalf-life

SQ · Abdomen · Daily fasted

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

AOD-9604

VIP

Primary target

β3-adrenergic receptor (proposed)Ng 2000

VPAC1 and VPAC2 G-protein-coupled receptorsUdupa 2025

Pathway

β3-AR activation → cAMP → hormone-sensitive lipase activation → triglyceride breakdown to FFA + glycerolNg 2000

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

Downstream effect

Lipolysis of adipose tissue triglycerides; FFA release for oxidation; minimal IGF-1 / insulin impactHeffernan 2001

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

Feedback intact?

No GH-axis or IGF-1 feedback

Yes — exogenous VIP acts as physiological agonist

Origin

Synthetic modified C-terminal hexadecapeptide fragment of human GH (176-191) with N-terminal Tyr substitutionNg 2000

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

Antibody development

—

02Dosage Protocols

Parameter

AOD-9604

VIP

Standard dose

250–300 mcg / dayHeffernan 2001

Anecdotal SQ range. Phase 2 trial dose 1 mg/day oral.

—

Frequency

Once daily, fasted

—

Lower / starter dose

150 mcg / day

—

Evidence basis

Phase 2 trials + animal-strongHeffernan 2001 Ng 2000

Phase 3 RCT (TESICO)Brown 2023

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

Duration

8–12 weeks per cycle

—

Reconstitution

Bacteriostatic water, 1 mL per 2 mg vial → 2 mg/mL

Lyophilized powder reconstituted with sterile diluent per protocol

Timing

Morning fasted preferred (pre-cardio)

Aligns with circadian lipolysis.

—

Half-life

~30 min plasma

~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

AOD-9604

VIP

Injection site reaction

Mild erythema

—

GI symptoms

Rare mild nausea

Nausea, diarrhea (VIP is endogenous GI peptide)

Cardiovascular

Possible mild HR increase via β3-AR (theoretical β1 cross-reactivity)

—

IGF-1 elevation

None — designed to lack GH-axis activityHeffernan 2001

—

Insulin sensitivity

Neutral — no glucose impairmentHeffernan 2001

—

Cancer risk

No GH/IGF-1 axis activity → lower theoretical risk vs HGH

—

Pregnancy / OB

Avoid

—

Hypotension

—

Transient vasodilation-related blood pressure drop

Tachycardia

—

Reflex tachycardia secondary to vasodilation

Infusion site reactions

—

Erythema, phlebitis (IV administration)

Overall tolerability

—

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

Absolute Contraindications

AOD-9604

·Pregnancy / breastfeeding
·Severe cardiovascular disease (caution with β-receptor agonists)

VIP

·Known hypersensitivity to aviptadil or formulation components

Relative Contraindications

AOD-9604

·Concurrent β-blocker therapy (theoretical antagonism)
·Pheochromocytoma

VIP

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

05Administration Protocol

Parameter

AOD-9604

VIP

1. Reconstitution

Add 1 mL bacteriostatic water to 2 mg vial → 2 mg/mL = 200 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 preferred. 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

Morning, fasted, ideally pre-cardio for amplified fat oxidation.

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

AOD-9604

+ MOTS-c

Moderate

View MOTS-c →

AOD-9604 mobilises FFAs from adipose via β3-AR; MOTS-c upregulates AMPK / PGC-1α / FAO machinery so that mobilised FFAs are efficiently oxidised. The pathways are sequential — supply (AOD) plus demand (MOTS-c) — and produce more durable lipolytic effects than either alone in anecdotal protocols.

AOD-9604: 250–300 mcg SQ · morning fasted (daily)
MOTS-c: 5 mg SQ · 2–3× per week (pre-workout)
Primary benefit: Fat mobilisation + mitochondrial oxidation, no IGF-1 concern

VIP

— no documented stacks