What it is
Vasoactive intestinal peptide (VIP) is an endogenous 28-amino-acid neuropeptide, first isolated from hog small intestine in 1970, that acts as a vasodilator and immune modulator in the gut, lungs, and nervous system; aviptadil is its synthetic form. It appears in research on erectile dysfunction, pulmonary hypertension, sarcoidosis, and acute respiratory failure. An aviptadil and phentolamine injection for erectile dysfunction is approved in a small number of countries, while other uses, including respiratory indications, remain investigational in the US and EU.
How it works
VIP binds the VPAC1 and VPAC2 receptors, raising intracellular cyclic AMP, which relaxes vascular and erectile smooth muscle. In immune cells it has been reported to lower TNF-alpha production and promote regulatory T cells.
Regulatory status
- Cosmetic ingredient
- Research compound
- In clinical trials
- Approved medicine
Not approved as a medicine by the FDA or the EMA. Some are registered in individual countries. Supplied for laboratory research only.
What published research is studying
- Intracavernosal aviptadil with phentolamine in erectile dysfunction, including men unresponsive to other injectables
- Intravenous aviptadil in COVID-19 respiratory failure (Phase 2/3 and Phase 3 trials)
- Inhaled VIP in pulmonary hypertension and pulmonary sarcoidosis
- Immune regulation in the lung, including TNF-alpha production and regulatory T cells
Key findings
In the placebo-controlled phase of a multicentre double-blind study in 171 men with mainly nonpsychogenic erectile dysfunction, 75% responded to intracavernosal VIP with the lower phentolamine dose versus 12% on placebo, with transient facial flushing after 40% of 1,711 injections.
Dinsmore WW et al., BJU Int 1999In the TESICO randomised, placebo-controlled trial in 461 adults with COVID-19-associated acute hypoxaemic respiratory failure, intravenous aviptadil did not improve the day-90 recovery outcome (odds ratio 1.11, 95% CI 0.80 to 1.55), 90-day mortality was 38% versus 36% on placebo, and the aviptadil comparison was stopped for futility.
Brown SM et al., Lancet Respir Med 2023In a 196-patient multicentre placebo-controlled trial in critical COVID-19 respiratory failure, 3 days of intravenous aviptadil did not significantly improve the primary endpoint of being alive and free of respiratory failure at day 60 (odds ratio 1.6, 95% CI 0.86 to 3.11).
Youssef JG et al., Crit Care Med 2022In an open Phase 2 study, 20 patients with active sarcoidosis inhaled nebulised VIP for 4 weeks; it was well tolerated, significantly reduced TNF-alpha production by bronchoalveolar lavage cells, and increased regulatory-type CD4+ T cells.
Prasse A et al., Am J Respir Crit Care Med 2010In 20 patients with pulmonary hypertension, a single inhaled dose of aviptadil during right-heart catheterisation produced small, short-lived selective pulmonary vasodilation, with 6 patients showing a reduction in pulmonary vascular resistance of more than 20%.
Leuchte HH et al., Eur Respir J 2008
What the studies measured
Study durations
- Erectile dysfunction study: up to 12 self-administered injections over 6 months in the placebo-controlled phase (Dinsmore et al., BJU Int 1999).
- TESICO trial: daily 12-hour infusions for 3 days, with the primary outcome assessed at day 90 (Brown et al., Lancet Respir Med 2023).
- Critical COVID-19 trial: 3 days of intravenous infusion, with outcomes at day 60 (Youssef et al., Crit Care Med 2022).
- Sarcoidosis study: 4 weeks of nebulised VIP (Prasse et al., Am J Respir Crit Care Med 2010).
Endpoints
- Erection suitable for intercourse, and adverse events per injection
- Six-category ordinal recovery outcome and mortality at day 90
- Alive and free of respiratory failure at day 60
- TNF-alpha production and regulatory T cells in bronchoalveolar lavage
- Pulmonary vascular resistance and haemodynamics during right-heart catheterisation
How strong is the evidence?
Randomised human trials exist, with the strongest positive data for the aviptadil and phentolamine injection in erectile dysfunction, while the largest critical-care trial found no benefit in COVID-19 respiratory failure and the lung inflammation and pulmonary hypertension studies are small.
Common questions
Is VIP an approved medicine?
Research compound. Not approved as a medicine by the FDA or the EMA. Some are registered in individual countries. Supplied for laboratory research only.
How much human research is there on VIP?
Randomised human trials exist, with the strongest positive data for the aviptadil and phentolamine injection in erectile dysfunction, while the largest critical-care trial found no benefit in COVID-19 respiratory failure and the lung inflammation and pulmonary hypertension studies are small.
Does UU supply VIP?
Yes, as premium-grade research material for laboratory use. Every batch is tested by an independent lab and the certificate of analysis is published.