Neuropeptide Research

VIP: Vasoactive Intestinal Peptide Research Data

A conservative review of VIP: its structure and receptors, the animal data on circadian timing and inflammation, the small human studies, the aviptadil COVID-19 trials, and where regulators stand in 2026.

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Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 12, 2026: Initial publication, built from a source-by-source check of the VIP literature, ClinicalTrials.gov, FDA and EMA records, India’s 2022 new-drug approvals list, the Scottish Medicines Consortium advice and WADA. It separates receptor, animal and human evidence and contains no dosing information.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide that widens blood vessels and calms immune signalling in animal models, but no VIP medicine has shown a clear benefit in a large controlled trial. Its synthetic form, aviptadil, missed the primary endpoints of two US trials in critical COVID-19, one of them an NIH trial stopped for futility.[1][2] The positive human data are small: uncontrolled lung studies of 8 to 20 patients and one 80-patient inhaled COVID-19 trial.[3][4][5][6]

Aviptadil is not FDA-approved. India authorised an aviptadil injection in April 2022 for restricted emergency use in severe COVID-19 with acute respiratory distress syndrome, and a combination with phentolamine is a prescription treatment for erectile dysfunction in the UK.[7][8][9] No UAE registration of VIP as a medicine was found. Remy Research sells it for in-vitro laboratory research only, not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is VIP?

VIP is a linear peptide of 28 amino acids, His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn, ending in an asparagine amide. It is cut from a larger precursor encoded by the VIP gene, which also yields a related peptide, PHM-27.[10] Sami Said and Viktor Mutt isolated it from hog small intestine in 1970 and reported widened blood vessels, falling blood pressure, higher cardiac output and faster breathing in animals.[11]

VIP belongs to the same peptide superfamily as glucagon, GLP-1, secretin, GIP and GHRH, and it is closely related to PACAP.[12] Aviptadil is the drug name for synthetic VIP.[2] The molecule weighs about 3.3 kDa; PubChem draws it as the free acid rather than the natural amide, so its formula differs slightly from the native peptide.[13]

Receptors and What VIP Does

VIP acts mainly through two class B G-protein-coupled receptors, VPAC1 and VPAC2, which bind VIP and PACAP with high affinity; a third receptor, PAC1, is selective for PACAP.[12] In the body VIP works mostly as a local nerve signal rather than a circulating hormone: in volunteers, infused VIP left the blood with a half-time of about one minute.[14]

VIP — Receptors and Reported Roles
Receptor or role What was reported Evidence type
VPAC1 and VPAC2 Bind VIP and PACAP with high affinity; class B receptors Receptor pharmacology
PAC1 Selective for PACAP rather than VIP Receptor pharmacology
Blood vessels Vasodilation and lower blood pressure in animals; short-lived lung vasodilation in patients Animal, small human
Circadian timing Mice lacking VPAC2 cannot sustain normal daily rhythms Animal (knockout)
Immune signalling Milder arthritis and colitis in mouse models; more regulatory T cells in a small patient study Animal, small human
Gut secretion Tumours that over-secrete VIP cause watery diarrhoea and low potassium Human disease

Mice without the VPAC2 receptor lost their normal daily rest–activity rhythm and the rhythmic clock-gene activity of the brain’s master clock.[15] In mice, VIP reduced the severity of collagen-induced arthritis and of chemically induced colitis, including when given after the disease began.[16][17] The picture is not uniform: mice that cannot make VIP developed milder colitis than normal mice, not worse.[18]

VIPoma: What Too Much VIP Does

The clearest human evidence on sustained VIP excess comes from VIPoma, a rare and mostly malignant neuroendocrine tumour. Its unregulated VIP secretion causes watery diarrhoea, low blood potassium and a lack of stomach acid.[19] In 1978, volunteer infusions raised plasma VIP into the range seen with these tumours and caused flushing and a faster pulse; the same study found no sign that VIP acts as a circulating hormone under normal conditions.[14]

Human Data: What Exists

The human literature is small, and most of it comes from lung disease and COVID-19:

A 2025 meta-analysis of aviptadil in acute respiratory distress pooled two randomised trials and found no survival difference (odds ratio 1.01; 95% CI 0.72–1.42).[22] Of 23 ClinicalTrials.gov records returned by a search for aviptadil or VIP, 10 are COVID-19 studies and 6 are headache or migraine studies.[23]

Claims Online and What Backs Them

What Has Been Published on Safety

There are no long-term human safety data.

Regulatory Status in 2026

Where VIP stands as of October 12, 2026.
  • United States. No aviptadil product is FDA-approved.[7] FDA granted aviptadil an orphan designation for sarcoidosis in July 2020, which is not an approval.[26] VIP is in Category 1 of FDA’s 503A compounding nominations, “bulk drug substances under evaluation”; that is not an approval either.[27]
  • European Union. No EU authorisation was found. Aviptadil holds EU orphan designations for sarcoidosis (2007) and acute respiratory distress syndrome (February 2026); EMA notes that a designation does not mean a medicine is authorised.[28][29]
  • India. The national drug regulator authorised aviptadil injection on April 29, 2022 for restricted emergency use in patients with severe COVID-19 and acute respiratory distress syndrome, in light of the COVID-19 outbreak.[8]
  • United Kingdom. Aviptadil combined with phentolamine (Invicorp) is a prescription treatment for erectile dysfunction; Scotland’s medicines consortium accepted it for restricted NHS use in 2017.[9]
  • UAE. No UAE registration of VIP as a medicine was found. Remy Research sells it for in-vitro laboratory research only, not for human or veterinary use.
  • Sport. VIP is not named on WADA’s 2026 or 2027 Prohibited List. Because aviptadil holds national approvals, WADA’s S0 clause for unapproved substances does not obviously apply, but there is no VIP-specific ruling; athletes should ask their anti-doping organisation.[30][31]

What the VIP Literature Does Not Yet Give You

These gaps are not arguments against studying VIP. They are arguments against overselling it.

Where VIP Fits in an RUO Research Catalog

For research use, VIP belongs with the neuropeptide and immune-signalling research tools: a defined VPAC-receptor agonist for cell-culture and animal-model work on vasodilation, circadian signalling and inflammation. Remy Research sells the Genovare VIP 25mg AQ pen; Genovare is the brand and manufacturer. The pen is labelled 25mg, and Genovare supplies no sequence or salt specification.

No independent batch report has been published for this pen, so its identity, quantity and purity are unverified; its product page lists its testing status as “Independent testing not supplied”. Every report Remy Research has published is in the lab results library. The pen is supplied for in-vitro laboratory research only, not for human or veterinary use, and is not framed for treatment.

For researchers reading this page as a starting point, the most useful adjacent references on this site are the thymosin alpha-1 review, the KPV review, the COA and HPLC purity guide, and the pen and vial comparison.

Our Research Standards

This article prioritizes primary literature, trial registries and regulator records, and keeps receptor, animal and human evidence apart. Where the human record is thin, we say so directly. No therapeutic, human-use, or veterinary-use claim is made here. Read our editorial policy →

RP
Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

About the editorial team →

VIP Research FAQ

What is VIP peptide?

VIP, or vasoactive intestinal peptide, is a natural 28-amino-acid neuropeptide first isolated from hog intestine in 1970. It acts through the VPAC1 and VPAC2 receptors, which it shares with the related peptide PACAP. Its synthetic drug form is called aviptadil.[11][12]

What are the claimed benefits of VIP, and what does the evidence show?

Claims online include lung protection, anti-inflammatory effects and help with “mould illness”. The support is mouse models, small uncontrolled lung studies and a single confounded case report, while the two largest US randomised trials of aviptadil, in critical COVID-19, missed their primary endpoints.[5][2][24]

Is VIP the same as aviptadil?

Aviptadil is the drug name for synthetic VIP, with the same sequence. The Genovare pen is a research product, not a licensed aviptadil medicine. The aviptadil medicines found are an injection authorised in India in April 2022 for restricted emergency use in severe COVID-19 with acute respiratory distress syndrome, and a combination with phentolamine licensed for erectile dysfunction.[2][8][9]

Did aviptadil work for COVID-19?

Not in the largest trials. A 196-patient US trial missed its primary endpoint, and the NIH-funded TESICO trial of 461 patients was stopped for futility with 90-day mortality of 38% against 36% on placebo. An 80-patient inhaled trial in Turkey reported earlier discharge, 7.8 against 10 days.[1][2][6]

Is VIP approved by the FDA or in the UAE?

No. No aviptadil product is FDA-approved; FDA has granted an orphan designation for sarcoidosis, and VIP sits in Category 1, “under evaluation”, of its compounding nominations. No UAE registration of VIP as a medicine was found.[7][26][27]

How does VIP work?

VIP binds VPAC receptors on blood vessels, smooth muscle, immune cells and neurons, including the brain’s master clock. In mice, losing the VPAC2 receptor disrupted daily rhythms. In the body it acts mostly as a short-lived local nerve signal rather than a hormone.[12][15][14]

Is VIP on the WADA Prohibited List?

It is not named on the 2026 or 2027 List. Because aviptadil holds national approvals, the S0 clause for unapproved substances does not obviously apply, but there is no VIP-specific ruling; athletes should ask their anti-doping organisation.[30][31]

Has the Genovare VIP pen been independently tested?

No independent batch report has been published for this pen, so its identity, quantity and purity are unverified. Its product page states “Independent testing not supplied”, and every report Remy Research has published is listed in the lab results library.

Sources

  1. Youssef JG, Lavin P, Schoenfeld DA, et al. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Crit Care Med. 2022;50(11):1545-1554. doi: 10.1097/CCM.0000000000005660 · PMID: 36044317 ↩
  2. Brown SM, Barkauskas CE, Grund B, et al; ACTIV-3b/TESICO Study Group. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. 2023;11(9):791-803. doi: 10.1016/S2213-2600(23)00147-9 · PMID: 37348524 ↩
  3. Petkov V, Mosgoeller W, Ziesche R, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 2003;111(9):1339-1346. doi: 10.1172/JCI17500 · PMID: 12727925 ↩
  4. Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294. doi: 10.1183/09031936.00050008 · PMID: 18978135 ↩
  5. Prasse A, Zissel G, Lützen N, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med. 2010;182(4):540-548. doi: 10.1164/rccm.200909-1451OC · PMID: 20442436 ↩
  6. Esendagli D, Sarı N, Akhan S, et al. Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19. Med Princ Pract. 2025;34(2):191-200. doi: 10.1159/000543773 · PMID: 39870064 ↩
  7. U.S. Food and Drug Administration. Drugs@FDA data (openFDA drugsfda endpoint) searched for the active ingredient aviptadil, October 12, 2026: no matching application. api.fda.gov ↩
  8. Central Drugs Standard Control Organisation (India). List of new drugs approved in the year 2022, entry 13: aviptadil bulk and aviptadil injection, for patients with severe COVID-19 with acute respiratory distress syndrome, for restricted emergency use in light of the COVID-19 outbreak; date of issue April 29, 2022. cdsco.gov.in ↩
  9. Scottish Medicines Consortium. Aviptadil/phentolamine mesilate (Invicorp), SMC No 1284/17: accepted for restricted use within NHS Scotland for erectile dysfunction, November 10, 2017. scottishmedicines.org.uk ↩
  10. UniProt Consortium. UniProtKB P01282, VIP peptides (human): vasoactive intestinal peptide, residues 125–152, with a C-terminal asparagine amide; the same precursor yields PHM-27. uniprot.org/uniprotkb/P01282 ↩
  11. Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. 1970;169(3951):1217-1218. doi: 10.1126/science.169.3951.1217 · PMID: 5450698 ↩
  12. Harmar AJ, Fahrenkrug J, Gozes I, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012;166(1):4-17. doi: 10.1111/j.1476-5381.2012.01871.x · PMID: 22289055 ↩
  13. National Center for Biotechnology Information. PubChem Compound Summary for CID 16132300, aviptadil (record drawn as the free acid). pubchem.ncbi.nlm.nih.gov/compound/16132300 ↩
  14. Domschke S, Domschke W, Bloom SR, et al. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut. 1978;19(11):1049-1053. doi: 10.1136/gut.19.11.1049 · PMID: 730072 ↩
  15. Harmar AJ, Marston HM, Shen S, et al. The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Cell. 2002;109(4):497-508. doi: 10.1016/s0092-8674(02)00736-5 · PMID: 12086606 ↩
  16. Delgado M, Abad C, Martinez C, et al. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med. 2001;7(5):563-568. doi: 10.1038/87887 · PMID: 11329057 ↩
  17. Abad C, Martinez C, Juarranz MG, et al. Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn’s disease. Gastroenterology. 2003;124(4):961-971. doi: 10.1053/gast.2003.50141 · PMID: 12671893 ↩
  18. Abad C, Cheung-Lau G, Coûté-Monvoisin AC, et al. Vasoactive intestinal peptide-deficient mice exhibit reduced pathology in trinitrobenzene sulfonic acid-induced colitis. Neuroimmunomodulation. 2015;22(3):203-212. doi: 10.1159/000364912 · PMID: 25301381 ↩
  19. Karele EN. All you need to know about VIPoma: Review on the latest studies. Presse Med. 2024;53(2):104222. doi: 10.1016/j.lpm.2023.104222 · PMID: 38109967 ↩
  20. ClinicalTrials.gov. NCT03556020: phase 2 study of pemziviptadil (PB1046), a long-acting VIP analogue, in pulmonary arterial hypertension (sponsor PhaseBio Pharmaceuticals; terminated after 35 enrolments, "Study drug resupply delayed (Covid-19)"), checked October 12, 2026. clinicaltrials.gov/study/NCT03556020 ↩
  21. Pellesi L, Al-Karagholi MA, De Icco R, et al. Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial. JAMA Netw Open. 2021;4(8):e2118543. doi: 10.1001/jamanetworkopen.2021.18543 · PMID: 34357396 ↩
  22. Udupa AA, Todur P, Chaudhuri S, et al. Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis. Indian J Crit Care Med. 2025;29(11):942-953. doi: 10.5005/jp-journals-10071-25084 · PMID: 41368449 ↩
  23. ClinicalTrials.gov search for aviptadil or vasoactive intestinal peptide, run October 12, 2026 (23 records: 10 COVID-19 studies, 6 headache or migraine studies, 3 pulmonary hypertension or COPD studies, 4 others). clinicaltrials.gov ↩
  24. Gunn SR, Gunn GG, Mueller FW. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures. Am J Case Rep. 2016;17:320-325. doi: 10.12659/ajcr.896949 · PMID: 27165859 ↩
  25. PubMed search for randomised controlled trials of intranasal VIP or aviptadil, run October 12, 2026 (4 records; none gives VIP as the treatment). pubmed.ncbi.nlm.nih.gov ↩
  26. U.S. Food and Drug Administration. Search Orphan Drug Designations and Approvals: aviptadil, treatment of sarcoidosis, designated July 23, 2020 (not FDA-approved for the orphan indication). accessdata.fda.gov ↩
  27. U.S. Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A: Categories 1–3 ("Vasoactive Intestinal Peptide" in Category 1, bulk drug substances under evaluation; updated May 14, 2026). fda.gov/media/94155 ↩
  28. European Medicines Agency. EU/3/07/473: orphan designation of aviptadil for the treatment of sarcoidosis (September 14, 2007). ema.europa.eu ↩
  29. European Medicines Agency. EU/3/26/3200: orphan designation of aviptadil for the treatment of acute respiratory distress syndrome (February 23, 2026); "Orphan designation does not mean the medicine is available or authorised for use." ema.europa.eu ↩
  30. World Anti-Doping Agency. 2026 Prohibited List (VIP and aviptadil are not named; class S0 covers substances with no current governmental approval for human therapeutic use). wada-ama.org ↩
  31. World Anti-Doping Agency. 2027 Prohibited List, approved September 10, 2026 and in force from January 1, 2027 (VIP and aviptadil are not named). wada-ama.org ↩

For catalog details, see the Genovare VIP 25mg AQ pen and the lab results library. For editorial standards, continue to the research standards page.

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