Side-by-side · Research reference

GLP-1 (7-37)vsVIP

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

BPhase 3HUMAN-REVIEWED9/42 cited

GLP-1 (7-37)

Incretin Hormone · Native Peptide

~2 minHalf-lifeAlavi 2021 Ding 2017

3297.7 DaMolecular weightAlavi 2021

1922Discovery year

Research use only · IV/SC in experimental settings

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

GLP-1 (7-37)

VIP

Primary target

GLP-1 receptor (class B GPCR)Koole 2015

VPAC1 and VPAC2 G-protein-coupled receptorsUdupa 2025

Pathway

GLP-1R activation → cAMP production → PKA signaling → insulin secretion (pancreatic β-cells)Lu 2025 Koole 2015

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

Downstream effect

Glucose-dependent insulin release, glucagon suppression, delayed gastric emptying, reduced food intakeLu 2025 Ding 2017

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

Feedback intact?

Yes — physiological secretion and degradation preserved

Yes — exogenous VIP acts as physiological agonist

Origin

Endogenous peptide cleaved from proglucagon in intestinal L cells; secreted postprandially

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

Antibody development

—

02Dosage Protocols

Parameter

GLP-1 (7-37)

VIP

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.

—

Half-life

~2 minutes (plasma)Alavi 2021 Ding 2017

Requires continuous infusion for sustained effect.

~2 minutes (plasma)

Rapid clearance necessitates continuous infusion.

Modified analogues

t½ extended to 13 h (liraglutide), 165 h (semaglutide)

Via DPP-4 resistance + fatty acid acylation.

—

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)

Evidence basis

—

Phase 3 RCT (TESICO)Brown 2023

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

Reconstitution

—

Lyophilized powder reconstituted with sterile diluent per protocol

03Metabolic / Fat Loss Evidence

Parameter

GLP-1 (7-37)

VIP

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

—

04Side Effects & Safety

Parameter

GLP-1 (7-37)

VIP

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

—

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

GLP-1 (7-37)

—

VIP

·Known hypersensitivity to aviptadil or formulation components

Relative Contraindications

GLP-1 (7-37)

—

VIP

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

05Administration Protocol

Parameter

GLP-1 (7-37)

VIP

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.

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

2. Storage

Lyophilised peptide stored at -20°C or below. Reconstituted solutions should be prepared fresh and used immediately due to rapid degradation.

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. 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).

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

4. Inhaled protocol (investigational)

—

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

5. Storage

—

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