VIP (Vasoactive Intestinal Peptide); Aviptadil (synthetic VIP); ZYESAMI; RLF-100
Vasoactive Intestinal Peptide (VIP); Vasoactive Intestinal Polypeptide; Aviptadil (INN for synthetic VIP)
Clinical trials showed mixed results. Benefits were seen on some measures but not others.
A natural peptide that relaxes blood vessels, reduces inflammation, and protects nerve cells throughout the body and brain. A synthetic version was tested in a large clinical trial for severe respiratory failure but did not meet its main treatment goal. Research into other potential uses continues.
This entry is a cited research summary, not an established treatment reference. Dosing language is included as source context, not as medical instruction.
VIP (Vasoactive Intestinal Peptide); Aviptadil (synthetic VIP); ZYESAMI; RLF-100 has moderate clinical evidence but is not FDA-approved.
Clinical trials showed mixed results. Benefits were seen on some measures but not others.
Safety Summary
The safety profile of VIP/aviptadil is generally benign in available clinical data. No dose-limiting toxicities were identified in Phase I studies or the 60-day RCT (PMC9555831; NCT00004494). The TESICO trial reported no excess SAEs vs placebo (PMC10278994; PMID 37348524). Flushing, hypotension, and headache are the most commonly reported effects. No established drug-drug interactions are documented (Drugs.com aviptadil entry, DrugBank DB18634). No CYP-mediated metabolism (proteolytic clearance). No tolerance, tachyphylaxis, or withdrawal effects documented in studies up to 60 days (PMC9555831; IJCCM systematic review; FDA NDA multidisciplinary review). Animal chronic toxicity at supratherapeutic doses: mild dose-dependent histologic findings (renal interstitial inflammation, hepatic vacuolization, cardiac muscle fiber changes) generally absent at therapeutic exposures (PMC6982157; Frontiers Pharmacol 2021 doi:10.3389/fphar.2021.638128). No cancer signal in FAERS or WHO VigiBase surveillance. Long-term human safety data are limited. Note: PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) is completely unrelated to VIP therapy despite sharing the acronym.
Clinical check-in
If real-world use or exposure is being considered, review potential interactions, contraindications, and monitoring needs with a licensed clinician rather than relying on summary copy alone.
Cited sources
Every claim on this page links to one of the 12 sources below. Identifiers are PubMed (PMID), ClinicalTrials.gov (NCT), or DOI; click through to the source of record before acting on a claim.
- 1PMID 37348524PubMed
- 2The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled TrialReference
- 3VIP in the Treatment of Critical COVID-19 With Respiratory Failure: A Prospective Externally-Controlled TrialReference
- 4doi:10.1038/s41467-022-34629-3DOI
- 5PMID 3687785PubMed
- 6PMID 730072PubMed
- 7NCT03989817ClinicalTrials.gov
- 8A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune DiseasesReference
- 9Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetesReference
- 10Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functionsReference
- 11A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson's DiseaseReference
- 12Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal systemReference