VIP.
VIP (vasoactive intestinal peptide, also called vasoactive intestinal polypeptide) is a 28-amino-acid neuropeptide first isolated from porcine intestine in the early 1970s.
VIP (vasoactive intestinal peptide, also called vasoactive intestinal polypeptide) is a 28-amino-acid neuropeptide first isolated from porcine intestine in the early 1970s. VIP is research / preclinical, and PepCue grades its published evidence C tier (50/100). Also known as vasoactive intestinal peptide. This is a research reference, not medical or dosing advice.
What it is
VIP (vasoactive intestinal peptide, also called vasoactive intestinal polypeptide) is a 28-amino-acid neuropeptide first isolated from porcine intestine in the early 1970s. It is highly conserved across mammals and belongs to the secretin/glucagon peptide superfamily, sharing close homology with PACAP (pituitary adenylate cyclase-activating polypeptide). It is widely distributed in the central and peripheral nervous systems and in the gut, and is notably enriched in lung tissue. The synthetic form used in human trials is known as aviptadil.
How it works
VIP signals through two class B G-protein-coupled receptors, VPAC1 and VPAC2, both of which bind VIP and PACAP with high affinity (a related receptor, PAC1, is PACAP-selective). Receptor activation couples primarily to adenylate cyclase, raising intracellular cAMP, with secondary coupling to phospholipase C in some contexts. Downstream effects include smooth-muscle relaxation and vasodilation, bronchodilation, stimulation of exocrine and electrolyte secretion, glucose-dependent insulin secretion (largely via VPAC2), and broad immunomodulatory/anti-inflammatory actions that shift cytokine balance away from pro-inflammatory mediators. In the lung, VIP receptors are concentrated on alveolar type II cells, which is part of the rationale for studying it in acute lung injury.
Mechanism pathways
Shifting immune-cell behaviour and cytokine balance rather than simply stimulating immunity.
The immune system is regulated rather than merely switched on or off, and the compounds here act as modulators: they can raise responsiveness in a suppressed state and dampen it in an overactive one, which is a different pharmacological category from a stimulant. The relevant machinery includes pattern-recognition receptors such as the Toll-like receptor family on dendritic cells and macrophages, the transcription factor NF-kB that governs pro-inflammatory gene expression, and the balance between T-helper subsets and regulatory T cells that determines the character of an immune response. One compound in this group is a thymus-derived peptide that acts principally through Toll-like receptors 2 and 9 on antigen-presenting cells. Downstream MyD88-dependent signalling promotes dendritic cell maturation, biases naive T cells toward a Th1 pattern, and augments natural killer and cytotoxic T cell activity, while also engaging regulatory pathways. Its usefulness is described in settings of immune exhaustion rather than in healthy immunity. A second acts largely without classical receptor engagement. It is taken into intestinal epithelial and immune cells by a proton-coupled di- and tripeptide transporter that is normally restricted to the small intestine but becomes induced in the colon during inflammation, meaning uptake is greatest precisely where inflammation is present. Once inside, it inhibits NF-kB and MAP kinase signalling, reducing pro-inflammatory cytokine output. A third is a widely distributed neuropeptide signalling through two class B G-protein-coupled receptors that raise cyclic AMP. Alongside smooth-muscle relaxation and secretory effects, it produces broad anti-inflammatory action by shifting cytokine balance away from pro-inflammatory mediators and supporting regulatory T cell populations. A fourth is included for its anti-inflammatory and anti-apoptotic effects, which accompany its better-known role in cytoskeletal regulation. Evidence quality varies considerably across this group and should not be averaged. One member is an approved medicine in a number of countries for specific infectious and immunological indications, giving it genuine human clinical grounding. Others rest largely on cell and animal work, with human data limited or confined to small studies. Immune modulation also carries a bidirectional risk that is rarely acknowledged: a compound capable of enhancing immune activity is in principle capable of aggravating autoimmune conditions, and that interaction is poorly characterised for most of this group.
The evidence
Human evidence is mixed and, for most systemic indications, limited. The strongest, most rigorous human data come from TESICO (ACTIV-3b), a randomized, placebo-controlled trial of intravenous aviptadil in COVID-19-associated hypoxaemic respiratory failure published in Lancet Respiratory Medicine (2023); it enrolled ~471 randomized participants and was stopped for futility, finding no improvement in clinical outcomes versus placebo. The earlier enthusiasm rested largely on small open-label series and preclinical/animal models of acute lung injury and cytokine suppression, which did not translate into proven benefit in the controlled setting. The best-established human use is local, not systemic: aviptadil combined with phentolamine (Invicorp) is an approved intracavernosal injection for erectile dysfunction in several countries. VIP has also held orphan-drug designations for pulmonary hypertension and sarcoidosis, but those indications lack confirmatory pivotal trial evidence.
The evidence, in brief
An endogenous neuropeptide with pulmonary-vasodilatory and anti-inflammatory properties, investigated for pulmonary arterial hypertension (and as the analogue aviptadil). Evidence is largely preclinical or early-phase; an early study reported improvement with inhaled VIP, but later controlled trials were mixed/modest.
- Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertensionJ Clin Invest, 2003 (PMID 12727925)
Evidence maturity
An evidence-only reading: approval status, human vs preclinical data, mechanism and safety. Popularity never raises it. Research file #069
Some human signal atop preclinical work; gaps remain.
Some early human evidence exists but isn't definitive.
Claim receipts
Popular claims about VIP, checked against the state of the evidence. The verdict describes evidence maturity, never an invented study result.
The large randomized placebo-controlled trial of intravenous aviptadil was stopped for futility and found no improvement in clinical outcomes.
The aviptadil plus phentolamine intracavernosal combination is an approved product for erectile dysfunction in several countries.
Immunomodulatory effects are mechanistic and preclinical, and orphan designations for pulmonary hypertension and sarcoidosis lack confirmatory pivotal trials.
As a potent vasodilator and secretory peptide it can cause hypotension, flushing and diarrhea, and long-term systemic safety is not characterized.
Safety profile
As an endogenous vasodilator, systemic VIP/aviptadil can cause hypotension, flushing, and diarrhea, and intravenous infusion has been associated with these effects in trials. Excess endogenous VIP, as seen in VIPoma tumors, produces severe secretory (watery) diarrhea, hypokalemia, and dehydration, illustrating its potent secretory pharmacology. For intracavernosal use, the combination product is reported to carry low rates of penile pain and priapism relative to some other injectables. Long-term safety of systemic administration is not well characterized, and the controlled COVID-19 data did not establish a net clinical benefit; safety beyond the studied settings remains uncertain.
Compound notes
- VIP (Vasoactive Intestinal Peptide) is an endogenous neuropeptide with vasodilatory and anti-inflammatory/immune-modulating effects.
- Intranasal VIP and the analog aviptadil have been studied in specific investigational contexts (e.g. respiratory/inflammatory conditions).
- Not FDA-approved for most discussed uses; investigational.
- Can cause flushing/blood-pressure effects; medical context matters.
Regulatory status
VIP itself is not an FDA-approved drug; intravenous aviptadil is investigational in the United States and was studied under FDA mechanisms including orphan-drug designations (pulmonary hypertension, sarcoidosis) and emergency COVID-19 trials. The aviptadil/phentolamine combination (Invicorp) is approved for erectile dysfunction in several countries including the UK, Denmark, and New Zealand, but not broadly in the US.
Sold research-use-only; human evidence is limited or preclinical.
By the numbers
- 0128-amino-acid neuropeptide of the secretin/glucagon superfamily, closely related to PACAP
- 02Acts via class B GPCRs VPAC1 and VPAC2, signaling mainly through cAMP
- 03Causes vasodilation, bronchodilation, smooth-muscle relaxation, and has anti-inflammatory/immunomodulatory effects
- 04Enriched in the lung, which motivated trials in acute respiratory failure
- 05TESICO (2023), the largest controlled trial, found IV aviptadil gave no benefit in COVID-19 respiratory failure and was stopped for futility
- 06Approved (with phentolamine, as Invicorp) for erectile dysfunction in several countries, but VIP is not an approved systemic therapy
VIP: research formats
Choose the format you are researching to see route-specific notes.
Studied as an intravenous infusion under hospital supervision. There is no self-administered format.
VIP is a 28-amino-acid neuropeptide whose synthetic form, aviptadil, has been studied in humans as an intravenous infusion, most prominently in acute respiratory failure. Separately, the aviptadil and phentolamine combination Invicorp is approved in several countries including the UK, Denmark, and New Zealand for erectile dysfunction, where it is given by intracavernosal injection. Neither format is a general-purpose self-administered route, and this page presents no example schedule.
TESICO (2023), the largest controlled trial, found that intravenous aviptadil gave no benefit in COVID-19 respiratory failure and was stopped for futility. The route in that programme was a monitored hospital infusion.
VIP itself is not an FDA-approved drug. Intravenous aviptadil is investigational in the United States and was studied under FDA mechanisms including orphan-drug designations for pulmonary hypertension and sarcoidosis.
Sources
Every factual claim above resolves to a real, published source.
- Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR Review 1British Journal of Pharmacology, 2012; PMID 22289055
- Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trialLancet Respiratory Medicine, 2023; PMID 37348524
- Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction (Invicorp)Drugs, 2008; PMID 18485029
- Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetesFrontiers in Endocrinology, 2022; PMC9531956
Cite this page
PepCue. “VIP: the evidence.” PepCue, reviewed June 1, 2026. https://www.pepcue.app/p/vip.
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