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Peptide (natural hormone)Human trialsNot FDA approved

VIP

Vasoactive intestinal peptide

Last reviewed October 27, 2026 · 13 sources · Written for general readers · Compare with another compound →

The bottom line

VIP is a natural hormone that widens blood vessels and airways, and its lab made copy is called aviptadil. In the largest and best run trial, in people on breathing support with COVID-19, it did not improve survival or recovery. Small inhaled studies in lung disease looked hopeful but were tiny, and no aviptadil product is approved in the United States.

Where the evidence stands

What it is

VIP stands for vasoactive intestinal peptide. It is a natural signaling molecule of 28 amino acids, with the sequence HSDAVFTDNYTRLRKQMAVKKYLNSILN, made in the gut, the nerves and elsewhere in the body.[1]

Aviptadil is the lab made copy of the same peptide. It was studied as a drip into a vein in hospital, and as an inhaled mist.[2]

Outside the United States, an injection that combines VIP with phentolamine, another blood vessel widening drug, has been used to treat erectile dysfunction.[3][4]

Name
VIP (Vasoactive intestinal peptide)
Other names
aviptadil (the synthetic form), Zyesami (trial name)
Type
Peptide (natural hormone)
Sequence
HSDAVFTDNYTRLRKQMAVKKYLNSILN

How it works

VIP relaxes smooth muscle, the kind of muscle in blood vessel and airway walls.

  • It is a strong widener of airways and blood vessels and also affects immune cells.[5]
  • For COVID-19, researchers proposed that it protects the cells that make surfactant, the slippery film that keeps the tiny air sacs open, and calms inflammation, mostly based on cell studies.[2]
  • In people with sarcoidosis who inhaled it, immune cells washed out of the lungs made less of an inflammation signal and included more regulatory T cells, which calm immune attacks.[6]
  • In erections, VIP mainly works by helping the veins trap blood, while phentolamine boosts blood flowing in.[3]

The lung protection ideas came mainly from lab work and did not hold up in the large COVID-19 trial.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Most of the groundwork was in cells rather than animals

  • The proposed COVID-19 benefits, including blocking viral replication, protecting lung cells, calming immune cells and boosting surfactant, were supported mainly by lab cell studies.[2]
  • In lab dishes, VIP turned immature T cells into regulatory T cells, the cells that keep immune attacks in check.[6]
  • Reviews describe VIP as a potent widener of airways and blood vessels with immune calming effects, which led to interest in asthma, COPD and pulmonary hypertension.[5]

Limit: Lab findings about lung cells did not predict what happened in patients.

Human studies

Large IV trials in COVID-19 found no benefit; small inhaled studies were hopeful

  • COVID-19 breathing failure, 2022: 196 critically ill patients at ten US hospitals got an IV drip of aviptadil or placebo. The main goal, being alive and free of breathing failure at 60 days, was not met. Better survival was a secondary finding that the authors said needed testing.[7]
  • COVID-19, TESICO 2023: 471 patients were randomized and the trial was stopped early for futility. At 90 days recovery did not differ, and deaths were 38 percent with aviptadil versus 36 percent with placebo.[2]
  • In TESICO, a combined measure of serious problems in the first five days happened in 63 percent on aviptadil versus 56 percent on placebo, not a significant difference but not reassuring.[2] An editorial called it plainly a negative trial.[11]
  • Inhaled, COVID-19, 2025: 80 adults in hospital at nine centers inhaled aviptadil or placebo. Time to discharge was about 7.8 versus 10 days, lung scans improved more by day 28, and deaths were 5.1 versus 12.2 percent, though the trial was too small to judge deaths. No one dropped out because of side effects.[9]
  • Review, 2025: nine studies with 665 patients, most of them uncontrolled case series, found no survival benefit in the two randomized trials.[8]
  • Sarcoidosis, 2010: 20 people inhaled VIP for four weeks without a comparison group. Lung inflammation markers fell and it was well tolerated.[6]
  • Pulmonary hypertension, 2008: 20 people inhaled a single dose during heart testing. Lung vessels widened slightly for a short time, heart output improved, systemic blood pressure did not drop, and no side effects were reported.[10]
  • Erectile dysfunction, 2025: 308 men used VIP combined with phentolamine as a penile injection after other treatments failed. 59 percent found it effective, 22.5 percent had facial flushing and 1 man had priapism, a prolonged painful erection.[4]

Limit: The best evidence, from large IV trials in COVID-19, shows no benefit, and the hopeful inhaled studies were small or uncontrolled.

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Saves lives in severe COVID-19 and lung failure

No benefit in trials so far

In a 471 patient trial of people on oxygen or breathing support, an IV drip of aviptadil did not improve recovery at 90 days, and 38 percent died versus 36 percent with placebo. The trial was stopped early for futility.[2] A 196 patient trial also missed its main goal.[7] A 2025 review pooling the two controlled trials found no survival benefit, with an odds ratio of 1.01.[8]

Speeds lung recovery when inhaled

Mixed results

In one placebo controlled trial of 80 adults in hospital with COVID-19, those who inhaled aviptadil went home after about 7.8 days versus 10 days, a difference just at the edge of statistical significance, and lung scans looked better at day 28.[9] This single small trial has not been confirmed.

Calms lung inflammation such as sarcoidosis

Mixed results

In a study of 20 people with active sarcoidosis who inhaled VIP for four weeks, lung immune cells made less of the inflammation signal TNF and calming regulatory T cells increased, and it was well tolerated.[6] There was no comparison group, and the study measured lab markers rather than breathing or symptoms.

Lowers high blood pressure in the lungs

Mixed results

In 20 people with pulmonary hypertension, a single inhaled dose during a heart catheter test caused a small, short lived widening of lung blood vessels, and 6 of the 20 had a drop of more than 20 percent in lung vessel resistance.[10] No long term controlled trial results were found.

Treats erectile dysfunction

Mixed results

Only as an injection into the penis combined with phentolamine. A review reported it worked in at least 80 percent of men in clinical studies.[3] In a 2025 look back at 308 men whose earlier treatments failed, 59 percent found it effective, about 23 percent had facial flushing and one man had a prolonged painful erection.[4] VIP alone, in the forms sold online, has not been tested for this.

Known risks and side effects

  • No proven benefit where it was tested most. The largest trial was stopped for futility and found no improvement at 90 days, and pooled trials show no survival benefit.[2][8]
  • Flushing and low blood pressure. VIP widens blood vessels. Facial flushing affected about 23 percent of men using the penile injection, which is why IV use was studied only in monitored hospital settings.[4][2]
  • Serious problems not reduced in hospital. In the TESICO trial, serious problems in the first five days were somewhat more common with aviptadil than with placebo, 63 versus 56 percent.[2]
  • Prolonged erection with penile injection. In the combination injection used for erectile dysfunction, prolonged painful erection occurred in about 1 in 300 men.[4]
  • Unregulated products. No aviptadil product has a US drug label, and VIP sits only in FDA's under evaluation compounding category, so material sold online has had no FDA review of purity or sterility.[12][13]

Regulatory status

Today: There is no approved aviptadil product in the United States, and a search of the national drug label database returns no results.[12] The COVID-19 trials were run under an FDA investigational new drug protocol, not under an approval.[2] FDA lists vasoactive intestinal peptide in category 1 of its 503A bulk drug substances list, meaning it is still under evaluation for pharmacy compounding, not cleared.[13]

  1. A 196 patient US trial in critical COVID-19 misses its main goal.[7]
  2. An independent safety board recommends stopping the larger TESICO trial for futility.[2]
  3. TESICO results show no benefit at 90 days, alongside an editorial calling it a negative trial.[2][11]
  4. An 80 person inhaled trial reports shorter hospital stays, and a review of all studies finds no survival benefit.[9][8]
  5. FDA's 503A bulks list shows vasoactive intestinal peptide in category 1, under evaluation.[13]

Sources

  1. UniProt Consortium. VIP peptides, human. UniProtKB entry P01282. UniProt P01282
  2. Brown SM, Barkauskas CE, Grund B, et al. 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. PMID 37348524
  3. Dinsmore WW, Wyllie MG. Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction. BJU Int. 2008;102(8):933-937. PMID 18485029
  4. Al-Mitwalli A, Holden F, Di Giovanni A, et al. Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction. J Sex Med. 2025;22(5):726-730. PMID 40192471
  5. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Evangelopoulou E, Mathioudakis GA. Vasoactive intestinal Peptide inhaled agonists: potential role in respiratory therapeutics. Hippokratia. 2013;17(1):12-16. PMID 23935337
  6. Prasse A, Zissel G, Lutzen N, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med. 2010;182(4):540-548. PMID 20442436
  7. 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. PMID 36044317
  8. 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. PMID 41368449
  9. Esendagli D, Sari 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. PMID 39870064
  10. Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294. PMID 18978135
  11. Lee WL, Slutsky AS. A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure. Lancet Respir Med. 2023;11:759-760. doi 10.1016/S2213-2600(23)00218-7
  12. U.S. National Library of Medicine. DailyMed search for aviptadil, accessed October 2026. DailyMed, no results
  13. U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (category lists). Updated May 14, 2026. FDA 503A category lists
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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