VIP (Vasoactive Intestinal Peptide)
Evidence: CImmune / Inflammation
Evidence Snapshot
Regulatory Context
Investigational for the U.S. indications reviewed. FDA records list orphan-drug designations for aviptadil for pulmonary arterial hypertension, designated February 22, 2005, and sarcoidosis, designated July 23, 2020. FDA lists neither orphan indication as approved. Orphan designation is not marketing approval and does not establish efficacy, safety, product quality, or legal availability of unapproved formulations.
Research Takeaway
VIP (Vasoactive Intestinal Peptide) is represented under the canonical identity Vasoactive intestinal peptide; listed aliases refer to this identity unless a formulation-specific distinction is stated.
See all 7 evidence claims →Quick Summary
VIP is a long-studied endogenous neuropeptide with broad vascular, pulmonary, gastrointestinal, neural, and immune effects. Human aviptadil trials are indication- and route-specific and have produced mixed results: a 2025 phase II trial of inhaled aviptadil in hospitalized COVID-19 pneumonia reported a borderline-shorter mean time to discharge, lower day-7 dyspnea, and greater day-28 CT improvement (mortality numerically lower but not statistically significant), while intravenous aviptadil showed no benefit in the large TESICO critical-COVID-19 trial.
Mechanism & Research Overview
VIP is an endogenous 28-amino-acid neuropeptide that signals mainly through VPAC receptors and can influence vascular tone, smooth muscle, secretion, immune signaling, and pulmonary physiology. Aviptadil is synthetic human VIP used in investigational formulations, and evidence remains route- and indication-specific.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
VIP (Vasoactive Intestinal Peptide) is represented under the canonical identity Vasoactive intestinal peptide; listed aliases refer to this identity unless a formulation-specific distinction is stated.
Supported
Human evidence for VIP (Vasoactive Intestinal Peptide) is limited to the specific populations, routes, formulations, and outcomes in the linked studies and must not be generalized beyond them.
Sources: Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension; Inhalation of vasoactive intestinal peptide in pulmonary hypertension; The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial; Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial; Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19
Supported
The main safety limitations for VIP (Vasoactive Intestinal Peptide) include vasodilation that may cause hypotension, flushing, tachycardia, headache, or dizziness. Safety findings are route- and population-specific: the 2025 inhaled-aviptadil phase II trial in hospitalized (non-ICU) COVID-19 pneumonia reported no treatment discontinuations from adverse effects in this small (n=80) trial, while the large intravenous-aviptadil TESICO trial, conducted in more severely ill patients with critical hypoxaemic respiratory failure, generated a larger and more serious safety-outcome dataset and found no evidence of benefit. Findings from these differently-routed trials in different populations cannot be directly compared or generalized to each other or to other formulations.
Sources: Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension; Inhalation of vasoactive intestinal peptide in pulmonary hypertension; The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial; Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial; Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19
Supported
FDA records list orphan-drug designations for aviptadil in pulmonary arterial hypertension and sarcoidosis. Orphan designation is not marketing approval, and FDA lists neither orphan indication as approved. Orphan designation does not establish efficacy, safety, product quality, or legal availability of unapproved formulations.
Sources: FDA Orphan Drug Designation: aviptadil for pulmonary arterial hypertension; NCT04311697: Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure; Vasoactive intestinal peptide compound record; FDA Orphan Drug Designation: aviptadil for sarcoidosis
Supported
Vasoactive intestinal peptide appears in FDA's 503A Category 1 list of bulk substances under evaluation. Category 1 means that a nomination contains sufficient information for continued evaluation while policy is pending. It does not mean FDA has approved the substance, found it safe and effective, or authorized a finished drug or dosing regimen.
Sources: FDA Bulk Drug Substances Used in Compounding Under Section 503A
Supported
An open Phase 2 study in 20 patients with pulmonary sarcoidosis used inhaled VIP for four weeks and reported changes in inflammatory or immunoregulatory markers. The study was small, uncontrolled, and not designed to establish definitive improvement in symptoms, lung function, hospitalization, organ damage, or survival.
Sources: Inhaled VIP in pulmonary sarcoidosis
Supported
VIP's vasodilatory and secretory pharmacology creates route- and dose-dependent safety concerns including hypotension, tachycardia, flushing, headache, dizziness, and diarrhea, as characterized in human physiology studies in healthy subjects. Inhaled evidence must not be used to establish subcutaneous or intravenous safety, and intravenous evidence must not validate intranasal or compounded use.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Vasodilation may cause hypotension, flushing, tachycardia, headache, or dizziness.Safety Consideration
Secretory and smooth-muscle effects may cause gastrointestinal symptoms.Safety Consideration
Safety and efficacy vary by route and formulation; inhaled and intravenous aviptadil cannot be generalized to other products.Safety Consideration
A 2025 phase II trial of inhaled aviptadil in hospitalized COVID-19 pneumonia reported a borderline-shorter time to discharge, lower day-7 dyspnea, and greater day-28 CT improvement; mortality was numerically lower but not statistically significant. This does not extend to intravenous, subcutaneous, compounded, or other formulations, nor to other indications such as pulmonary arterial hypertension or sarcoidosis.
Research Areas Being Studied
Research areas discussed on this page reflect the Immune / Inflammation category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19 (2025):
- Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial (2023):
- The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial (2022):
- Inhalation of vasoactive intestinal peptide in pulmonary hypertension (2008):
- Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension (2003):
- Cardiovascular effects of VIP in healthy subjects ():
- Inhaled VIP in pulmonary sarcoidosis ():
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19 | 2025 | 80 hospitalized adults with COVID-19 pneumonia and lung damage (mean age 55.8 ± 18.5 years; 33.8% female), 9 clinical centers | Multicenter, prospective, randomized, double-blind, placebo-controlled phase II trial of inhaled aviptadil (both arms received standard care) reported a borderline-shorter mean time to hospital discharge (7.8 vs 10 days, P = 0.049), lower dyspnea scores at day 7, and greater CT-score improvement at day 28. Mortality was numerically lower (5.1% vs 12.2%) but the difference was not statistically significant (P = 0.433). | Findings are specific to the inhaled route and this hospitalized COVID-19-pneumonia population; treatment was reported well-tolerated with no dropouts due to adverse effects in this small trial (n=80). This does not establish safety or efficacy for intravenous, subcutaneous, compounded, or other aviptadil formulations, nor for other indications (including pulmonary arterial hypertension or sarcoidosis, the orphan-designated indications) -- and stands in contrast to the negative result of the large TESICO intravenous-aviptadil trial, conducted in a more severely ill critical-hypoxaemic-respiratory-failure population with a larger, more serious safety-outcome dataset. Cross-trial comparison is limited by differing populations, severity, and routes. | |
| Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial | 2023 | Hospitalized adults with COVID-19-associated hypoxemic respiratory failure at 28 U.S. sites | TESICO found no evidence of benefit from aviptadil on the primary or secondary clinical endpoints. | Negative/neutral confirmatory evidence must remain prominent; route-specific safety monitoring was required. | |
| The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial | 2022 | Randomized trial in critical COVID-19 respiratory failure | The publication reported selected survival/recovery findings, but interpretation is limited by trial design, endpoints, and later larger evidence. | Route-specific adverse events and critical-illness context limit generalization. | |
| Inhalation of vasoactive intestinal peptide in pulmonary hypertension | 2008 | Patients with pulmonary hypertension in an acute inhalation study | Aviptadil aerosol caused small, temporary selective pulmonary vasodilation and improved selected hemodynamic measures. | Acute hemodynamic changes do not establish durable clinical outcomes or safety of other routes. | |
| Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension | 2003 | Small clinical investigation in primary pulmonary hypertension | Reported pulmonary hemodynamic and clinical observations after inhaled VIP/aviptadil in a small study. | Small, early study; does not establish approval or generalizable long-term efficacy. | |
| Cardiovascular effects of VIP in healthy subjects | A human physiology study characterized cardiovascular effects of VIP in healthy subjects, part of the foundational evidence for VIP's vasodilatory and secretory safety signal (hypotension, tachycardia). | ||||
| Inhaled VIP in pulmonary sarcoidosis | An open Phase 2 study in 20 patients with pulmonary sarcoidosis used inhaled VIP for four weeks and reported changes in inflammatory or immunoregulatory markers. The study was small, uncontrolled, and not designed to establish definitive improvement in symptoms, lung function, hospitalization, organ damage, or survival. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| FDA Bulk Drug Substances Used in Compounding Under Section 503A | 2026 | Vasoactive intestinal peptide appears in FDA's 503A Category 1 list of bulk substances under evaluation. Category 1 means a nomination contains sufficient information for continued evaluation while policy is pending. It does not mean FDA has approved the substance, found it safe and effective, or authorized a finished drug or dosing regimen. | |||
| FDA Orphan Drug Designation Record for Aviptadil | 2026 | Aviptadil has received orphan-drug designation for sarcoidosis. Orphan designation is not FDA approval and does not establish safety or effectiveness. | |||
| Vasoactive intestinal peptide compound record | 2026 | Chemical identity database record | PubChem records human VIP as a defined 28-amino-acid peptide compound. | Identity does not establish approval of a formulation or indication. | |
| FDA Orphan Drug Designation: aviptadil for sarcoidosis | 2020 | FDA orphan-drug designation record | FDA Office of Orphan Products Development (OOPD) record (grid key 751520) lists an orphan-drug designation for aviptadil, designated July 23, 2020, for the orphan designation "Treatment of sarcoidosis." Status: Designated. FDA orphan approval status: Not FDA Approved for Orphan Indication. | Orphan designation is not approval and does not establish efficacy, safety, product quality, or legal availability of unapproved formulations. | |
| NCT04311697: Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure | 2020 | Registered clinical trial in critical COVID-19 respiratory failure | Registry record documents the registered study design and status for intravenous aviptadil. | A registry entry is not a completed-results publication and does not establish benefit. | |
| FDA Orphan Drug Designation: aviptadil for pulmonary arterial hypertension | 2005 | FDA orphan-drug designation record | FDA lists aviptadil as designated for pulmonary arterial hypertension and explicitly states it is not FDA approved for the orphan indication. | Orphan designation is not approval and does not establish efficacy or safety. |
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system | 2019 | Narrative review | Reviews VIP physiology, receptors, and gastrointestinal actions. | Review article; not a primary efficacy trial. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational research summary only. Not medical advice, diagnosis, treatment guidance, or a user guide. Investigational and low-evidence compounds may have substantial unknowns.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-07-26.
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