VIP is an ingredient in a UK-licensed combination medicine for erectile dysfunction.

Why this note exists

VIP is an unusual case in this index. It has a licence, it has a large randomised trial funded by the US National Institutes of Health, and it has a live argument in the journals running through 2026. None of those three things points where the marketing points, and the mismatch is arithmetic before it is anything else: the licensed unit is 25 micrograms, and the common vial is ten milligrams.

In the index generated on September 3, 2026, 34 of 104 vendors carried a VIP listing — 49 listings, thirty-fourth of the 83 stocked compounds by vendor coverage.[31] Nine of the 49 spell out "vasoactive intestinal peptide" somewhere in the product name; none of them says aviptadil, Invicorp or ZYESAMI, the names under which the peptide has actually been licensed and tested.[31]

A note on what kind of evidence this is: every efficacy and safety figure below comes from a study in people, carrying its design and its participant count. Where the rationale for testing VIP in lung injury is preclinical, this note says so and does not report it as a result in humans. Sponsor announcements are labelled as sponsor announcements and set beside the peer-reviewed report of the same trial. pepmg does not convert a study protocol into a protocol for a research vial.

The licence

What is actually licensed, and at what dose

The licensed product is not VIP. It is a two-drug ampoule in which aviptadil is the smaller half by mass. The Scottish Medicines Consortium's assessment records the dosing in one paragraph: "The contents of one ampoule (aviptadil 25 micrograms / phentolamine 2mg) should be administered by direct intracavernous injection," that the resulting erection "does not exceed one hour," that "[i]njection frequency should not exceed once daily or 3 times weekly," and that "[i]nitial injections must be administered by medically trained personnel," with home injection permitted only after training and with review roughly every three months.[20] The All Wales assessment gives the marketing authorisation date as 21 April 2015.[19]

Both UK bodies accepted it, and both fenced it in. SMC advised on 10 November 2017 that aviptadil/phentolamine "is accepted for restricted use within NHS Scotland," restricted "for use in those who have failed on oral therapies (oral phosphodiesterase type-5 inhibitors) and other non-injectable formulations."[20] AWMSG recommended it with restrictions on 21 June 2017, for patients whose erectile dysfunction has not responded to oral PDE5 inhibitors — a resubmission, after AWMSG had previously issued a non-recommendation on the grounds that "the applicant company did not present sufficiently robust clinical and economic analyses to gain approval."[21][19]

In the United States there is nothing. A Drugs@FDA search on September 5, 2026 returns no approved product containing aviptadil.[25] In Europe the peptide holds two orphan designations, both granted to mondoBIOTECH: acute lung injury (EU/3/06/395, 28 August 2006) and sarcoidosis (EU/3/07/473, 14 September 2007).[23][24] An orphan designation is a development incentive, not a marketing authorisation — it is a statement about the rarity of a disease and a sponsor's intention to study it, and neither designation is evidence that the drug works.

The pivotal evidence

The study behind the licence was open-label, and the peptide arm did worse on the efficacy endpoint

The pivotal study, VP007, was "a multi-centre, open-label crossover study to investigate tolerability, efficacy and patient preference of intracavernosal injections of aviptadil / phentolamine and alprostadil," in men with erectile dysfunction of at least a year's standing; men with psychogenic aetiology were excluded.[20] It ran in two phases. In the dose-finding phase, a grade 3 erection — one suitable for intercourse — was achieved in significantly fewer patients on aviptadil/phentolamine (73%, 137 of 187) than on alprostadil (83%, 155 of 187), p=0.002.[20] Only patients who responded to both treatments continued, and in that enriched comparative phase the response rates were numerically similar, 84% against 83% of injections, with no statistical comparison performed.[20]

Figures as tabulated by the Scottish Medicines Consortium and the All Wales Therapeutics & Toxicology Centre from the company's submission.[19][20]

Where the licensed combination clearly did better was tolerability. SMC records that injections were "associated with significantly lower incidence of pain upon injection when compared with alprostadil; 3% versus 28% of injections, p<0.001," against "a significantly greater incidence of facial flushing; 16% ... versus 3%," and no cases of priapism with either treatment.[20] That is the trade the licence encodes: a peptide combination that is easier to tolerate than the standard second-line injection, on an efficacy comparison its own reviewers would not call equivalent. AWTTC's critique says so directly — "[i]t is therefore unclear whether the clinical effectiveness of aviptadil/phentolamine is equivalent to alprostadil" — and notes that 130 patients completed the first phase but only 107 started the second, with the reasons for dropping out unexplained.[19]

The most recent human data on this use are observational. A 2025 single-centre retrospective series from University College London Hospital followed 308 men referred for aviptadil/phentolamine after alprostadil either failed at maximum dose or caused intolerable pain, with a mean follow-up of 13.3 months: 182 (59%) resumed penetrative sexual activity at three months, 76% among those referred for pain against 36% among those referred for failure (p<0.0001), with facial flushing in 22.5% and ischaemic priapism in one patient (0.3%).[22] The authors describe the design's limits themselves — retrospective, single centre, no validated instrument for erectile function.[22]

The big trial

The largest randomised trial of the peptide was stopped for futility

TESICO, the ACTIV-3b platform's aviptadil comparison, is the study that settles what the internet still argues about. It enrolled 473 participants at 28 US sites between 21 April 2021 and 24 May 2022; 471 were randomly assigned to aviptadil or matched placebo, and 461 who received at least a partial infusion formed the modified intention-to-treat population, 231 on drug and 230 on placebo.[1][2] These were not marginal patients: 94% were in an intensive care unit at baseline and 40% were on invasive mechanical ventilation.[1]

The secondary outcomes went the same way. Up to day 90, 86 participants on aviptadil and 83 on placebo had died — a cumulative 38% against 36%, hazard ratio 1.04 (95% CI 0.77–1.41), p=0.78.[1] The primary safety composite through day 5 occurred in 146 of 231 (63%) on aviptadil against 129 of 230 (56%) on placebo, an odds ratio of 1.40 (95% CI 0.94–2.08), p=0.10 — not a signal of harm, but not reassurance either.[1] The authors' interpretation is one sentence long: aviptadil "did not significantly improve clinical outcomes up to day 90 when compared with placebo."[1] The trial was funded by the National Institutes of Health, which is to say by nobody selling the drug.[1]

The dose, reported as its source published it: aviptadil was given as a daily 12-hour infusion for three days, targeting 600 pmol/kg on day 1, 1200 pmol/kg on day 2 and 1800 pmol/kg on day 3.[1] That is a weight-based intravenous infusion target in an ICU, not an absolute amount, and pepmg does not convert one into the other.

The record

The same 196 patients, announced twice

Before TESICO there was the sponsor's own phase 2b/3 trial, NCT04311697, run at ten US hospitals: 203 randomised 2:1, 196 treated, 131 on aviptadil and 65 on placebo.[4] On 29 March 2021 a press release announced that the trial "Met the Primary Endpoint," reporting successful recovery from respiratory failure at day 28 (P = .014) and day 60 (P = .013) and a survival benefit (P < .001) "after controlling for ventilation status and treatment site."[5]

The peer-reviewed report of that same trial appeared in Critical Care Medicine in November 2022, with an author affiliated to the sponsor listed among the authors. Its own words: "The primary end point (alive and free from respiratory failure at day 60) did not reach statistical significance (odds ratio [OR], 1.6; 95% CI, 0.86–3.11) for patients treated with Aviptadil when controlling for baseline ventilation status as prespecified in the protocol."[6] Its conclusion opens: "The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo."[6] The paper then reports a secondary result — a two-fold odds of survival at day 60, OR 2.0 (95% CI 1.1–3.9), p = 0.035 — and argues from it that the benefit-risk balance is favourable.[6] An accompanying editorial in the same issue was titled "Aviptadil for COVID-19: A Case Study and Call to Action About the Challenges of Research During a Global Pandemic."[7]

A press release and the peer-reviewed paper describing the same 196 patients disagree about whether the primary endpoint was met, and the paper is the one that says it was not. The registry's own posted results give the unadjusted counts at day 28: 72 of 131 on aviptadil, 33 of 65 on placebo.[4]

The regulator's reading is on the record twice. On 4 November 2021 FDA declined an emergency use authorisation, and the sponsor's announcement quotes the agency as unable to issue it "due to insufficient data regarding the known and potential benefits ... and the known and potential risks," having reviewed safety in 131 randomised treated patients.[8] On 1 July 2022 FDA declined a second application, this one built on a post-hoc subgroup of patients who had also received remdesivir and continued to progress, after having declined Breakthrough Therapy Designation for the same subgroup.[9]

The pooled picture

Nine studies, 665 patients, and a pooled odds ratio of 1.01

The most recent synthesis is a systematic review and meta-analysis published in November 2025, searching six databases to October 2025. It found nine studies — two randomised controlled trials and seven case series — totalling 665 patients, 361 of whom received aviptadil, and pooling the two RCTs gave a survival odds ratio against placebo of 1.01 (95% CI 0.72–1.42, p = 0.93).[10] Across the case series, 48 of 54 patients (88.9%) survived, with consistent improvements in oxygenation and inflammatory markers — and case series have no control group, which is why the authors report them separately and conclude that "current evidence does not indicate a significant survival benefit."[10]

The journal ran an editorial alongside it, and its title is a fair summary of where critical-care medicine has landed on this peptide: Aviptadil in Acute Respiratory Distress Syndrome—Promise or Mirage?[11]

The live argument

One 80-patient trial found a two-day difference. Then the letters started.

The reason this note is being written in 2026 rather than 2023 is that the inhaled route is still being argued. A multicentre, double-blind, placebo-controlled randomised trial in Turkey enrolled 80 hospitalised COVID-19 patients across nine centres and reported an average time to discharge of 7.8 ± 4.0 days on inhaled aviptadil against 10 ± 5.0 days on placebo (p = 0.049), with a greater improvement in CT lung damage score at day 28 (p = 0.028) and deaths in 5.1% against 12.2%.[12] The authors' conclusion is carefully hedged: inhaled aviptadil "is well tolerated and can be used as a supplementary intervention to fasten the recovery of respiratory manifestations."[12]

A letter in the same journal then set out why the result is fragile. The trial's sample size was calculated on expected differences in oxygen saturation while its declared primary endpoint was time to discharge, which "risks inadequate power for the declared primary outcome"; saturation readings taken on supplemental oxygen hit a ceiling and compress the very variability the calculation rested on; patients who subsequently needed intensive care were excluded after randomisation, which "could disproportionately omit failures of therapy and inflate efficacy estimates"; and recruitment spanned pandemic waves whose variants differed in severity.[13] The trial's authors replied that excluding ICU patients was deliberate given a mechanism they describe as lung-protective rather than antiviral, and that recruitment ended in early December 2021, entirely within their country's Delta period.[14] This is what an unsettled 80-patient result looks like when it is examined properly — and it is a long way from what a product page means by "clinically studied."

The other two inhaled trials never reported. A European trial planned for 132 patients at 67 micrograms of inhaled aviptadil three times a day for ten days was terminated with 83 enrolled because, in the registry's own words, there were "very few hospitalized COVID patients" left who met eligibility.[15][16] The sponsor's inhaled phase 2/3 was terminated at 144 participants by "sponsor decision," with no results posted.[17] A terminated trial with no reported results is not a negative result; it is an absence of one.

Human pharmacology

Infused into people, VIP is reliably a headache

The cleanest human experiment on this peptide is not about lungs at all. In a randomised, double-blind, placebo-controlled crossover study at the Danish Headache Center, 21 patients with migraine without aura received a two-hour infusion of VIP or placebo on separate days. Fifteen of 21 (71%, 95% CI 48–89%) developed a migraine attack after VIP, against one (5%) after placebo, P < .001, and the induced attacks mimicked the patients' spontaneous ones.[18]

That study was designed to interrogate migraine mechanism, not to warn anyone off a vial, and it should not be read as a claim about what a research powder does to anybody. But it is the most reproducible thing controlled human research has to say about infusing this peptide into people, and five of the registered studies naming VIP as an intervention are provocation experiments of that kind.[27]

The gap

No registered study tests VIP for the reasons it is sold

A ClinicalTrials.gov search on 5 September 2026 returns 22 distinct studies naming aviptadil or vasoactive intestinal peptide as an intervention.[26][27] Eleven are COVID-19, ARDS or acute lung injury studies. Five are the headache provocation experiments. Two are in pulmonary arterial hypertension, using a long-acting analogue, pemziviptadil, whose phase 2 was terminated with 35 participants.[28] The remaining four include a study in Fontan-circulation patients, a study in COPD, and two in which VIP is measured rather than administered.[26][27]

None of the 22 tests VIP for gut health, immune modulation, circadian rhythm or chronic inflammatory response syndrome — which is roughly the entire list of reasons the research market gives for stocking it.[26][27]

On chronic inflammatory response syndrome specifically, the pairing of that term with this peptide returns two papers in PubMed. One is a 2016 case report of a single 25-year-old patient in whom VIP replacement was one of several simultaneous interventions alongside removing biotoxin exposure and dental extractions — a case report describes what happened to one person, and cannot separate one intervention from the others.[29] The other, published in April 2026, is a retrospective cohort of 188 adults at a single clinic in which VIP was a laboratory measurement rather than a treatment, and in which VIP showed no association with the study's exposure of interest while a different peptide did.[30] Neither is a trial of giving anybody VIP for that condition, because no such trial is registered.[26][27]

The market

A 25-microgram ampoule and a 10-milligram vial

The gap between what is licensed and what is sold is easiest to see as mass. The licensed unit holds 25 micrograms of aviptadil. The most common research vial holds 10 mg. One 10 mg vial therefore contains four hundred times the aviptadil in one licensed ampoule — which is a fact about how much peptide is in a container, and not a statement about what anyone should do with it.[20][31]

The forms differ as much as the amounts. The licensed article is a sterile ampoule of a fixed two-drug combination, delivered into one specific tissue by a route whose own label demands trained administration first.[20] What vendors ship is a single-peptide lyophilised powder, in 5, 6, 7.5, 10, 11.27, 12 and 20 mg vials and in multi-vial packs, one of them sold as an "Air Dispersal Kit."[31] Inhaled aviptadil has been studied, at 67 micrograms three times a day in a European protocol, and both inhaled trials stopped early without reporting.[15][16][17] pepmg makes no claim about the contents of any vendor's vial.

Three things this note is not saying

First, it is not saying aviptadil does not work for the thing it is licensed for. Two NHS bodies assessed it and accepted it with restrictions, and the largest clinical series in that indication reports that most men who had run out of other options resumed sexual activity on it.[20][21][22]

Second, it is not saying the lung hypothesis was foolish. The rationale — that VIP upregulates surfactant production and dampens cytokine signalling in the lung — is preclinical, as the trial reports themselves describe it, and it was serious enough that the NIH funded a 473-participant randomised trial to test it in people.[6][1] That is how a hypothesis is supposed to be resolved. It was resolved.

Third, it is not saying a VIP vial is dangerous. The strongest controlled human signal in this file is a headache-provocation study, and no controlled study has ever examined the products actually being sold.[18][26] Absence of evidence about those products is the finding here, not a safety verdict about them.

What this note is saying is narrow and checkable: the licence attached to this peptide is 25 micrograms of a two-drug ampoule, injected into the penis, for erectile dysfunction; the largest randomised trial of the peptide itself returned an odds ratio of 1.11 and was stopped for futility; and not one registered study tests VIP for the reasons it is stocked.[19][1][26]

Questions people are asking