Tradipitant (NEREUS, VLY-686)

Research snapshot

Peptide category	Not a peptide. Oral, non-peptide small-molecule NK-1 receptor antagonist
Primary research interest	Preventing vomiting caused by motion (approved) and by GLP-1 receptor agonist medicines (investigational); also in development for gastroparesis
Highest available evidence	Company-announced randomized, placebo-controlled Phase 3 results (Study 3601, not peer reviewed); FDA approval for motion-induced vomiting
Human research available	Yes. A Phase 2 study (116 adults) and a Phase 3 study (306 participants) in people given semaglutide, plus the program behind the motion-sickness approval
Development status	Phase 3 results reported for GLP-1-related vomiting; FDA discussion planned for 2027, then a supplemental application
Regulatory status	FDA approved December 2025 for preventing motion-induced vomiting; not approved for GLP-1-related vomiting

Technical identity

Primary name	Tradipitant
Alternative names	NEREUS (brand name), VLY-686, LY686017
Peptide sequence	Not applicable. Tradipitant is a small synthetic molecule, not a peptide
Amino-acid length	Not applicable
Molecular formula	C28H16ClF6N5O, per KEGG DRUG (entry D11728)
Molecular weight	587.90 g/mol, per KEGG DRUG
CAS Registry Number	622370-35-8, per KEGG DRUG
PubChem CID	9916461, as listed in the Wikipedia drug box; not independently confirmed against PubChem
UNII	Not reliably established
DrugBank ID	Not reliably established
Chemical modifications	Not applicable
Peptide class	Not a peptide. Small-molecule neurokinin-1 receptor antagonist
Primary biological target	Neurokinin-1 (NK-1, gene TACR1) receptor; blocks substance P signaling
Developer or originator	Eli Lilly and Company (as LY686017); licensed to Vanda Pharmaceuticals in 2012
Development status	FDA approved for motion-induced vomiting; Phase 3 results reported for GLP-1-related vomiting

What is tradipitant

Tradipitant, sold as NEREUS, is an oral medicine that blocks the neurokinin-1 (NK-1) receptor, the docking site for a messenger molecule called substance P. It is not a peptide. It has an entry here because its newest research concerns the nausea and vomiting that come with GLP-1 receptor agonist medicines such as semaglutide.

Eli Lilly first developed the compound as LY686017. Vanda Pharmaceuticals licensed it from Lilly in April 2012 for all human indications, and Vanda notes that earlier research had focused on alcohol dependence. Vanda has since developed it under the code VLY-686 and has pursued gastroparesis and vomiting as indications.

The FDA approved NEREUS in December 2025 for preventing vomiting induced by motion. Vanda is now developing it for vomiting associated with GLP-1 receptor agonists, a problem the company says is among the common reasons people stop treatment or fail to reach full doses. That framing is Vanda’s, and the trials so far measured vomiting over a short window, not whether people stay on treatment.

How does it work

Plain-English explanation

Vomiting is coordinated by a region at the base of the brain. Substance P is one of the chemical messengers that helps set it off, and it acts through NK-1 receptors. Tradipitant occupies those receptors so the signal is blocked. Vanda says it acts in the brain’s vomiting center, so it expects the effect to apply across GLP-1 medicines. Only semaglutide has been tested.

Technical explanation

Tradipitant is a selective, orally taken antagonist of the NK-1 receptor (TACR1). Vanda says it acts at the vomiting center, including the area postrema and the nucleus tractus solitarius, by blocking substance P signaling in those pathways. The Phase 3 announcement also describes a pooled exposure-response analysis of the Phase 2 and Phase 3 data in which the reduction in vomiting probability stayed stable across the semaglutide concentrations observed. That is a modeling analysis, not a trial with real-world dose escalation. Pharmacokinetic details for the GLP-1 setting, such as half-life, were not described in the sources reviewed.

Potential benefits and research applications

Vomiting with GLP-1 receptor agonists

Two randomized, placebo-controlled studies gave people a single 1 mg dose of semaglutide with no gradual build-up, a design chosen to produce a lot of vomiting. In the Phase 2 study (VP-VLY-686-2601), 116 overweight or obese adults without prior GLP-1 use were pretreated with tradipitant or placebo before a 1 mg Wegovy dose. Vomiting occurred in 29.3% (17 of 58) on tradipitant and 58.6% (34 of 58) on placebo (p=0.002), and vomiting together with significant nausea in 22.4% versus 48.3%.

In the Phase 3 study (Study 3601), any vomiting occurred in 43.0% (61 of 142) on tradipitant and 58.5% (96 of 164) on placebo (p=0.006), a 27% relative reduction and a 15.5 point absolute difference. Vomiting with severe nausea was 33.1% versus 50.6% (p=0.002). In analyses Vanda describes as post hoc, frequent vomiting on more than one day was 6.3% versus 15.9% and extreme vomiting (more than 10 episodes) was 2.8% versus 14.6%. Almost all vomiting occurred by day 2, and the gap between groups was largest on days 1 and 2.

Evidence strength: human randomized trials, but company-announced and not peer reviewed. The Phase 3 effect on any vomiting was smaller than the roughly 50% relative reduction seen in Phase 2. The trials do not show that people stay on a GLP-1 medicine longer, lose more weight, or respond the same way to tirzepatide or other agents. Gradual dose increases are the usual way these medicines are started, and neither study tested tradipitant under that approach.

Motion-induced vomiting

NEREUS is FDA approved for preventing vomiting caused by motion, an approval announced in December 2025. The trials behind that approval were not reviewed in detail for this page, and the prescribing information is the authoritative source for them.

What dosage information circulates

Figures in this section summarize amounts and schedules reported in published research or circulating online. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate.

Reported use or research objective	Route reported	Amount reported	Frequency reported	Reported duration	Evidence or source category
Phase 2 (VP-VLY-686-2601), vomiting after a 1 mg Wegovy challenge	Oral	85 mg per administration	Twice daily, as pretreatment before the single 1 mg Wegovy dose	Not stated in the sources reviewed	Company-reported human clinical trial (trade press coverage)
Phase 3 (Study 3601), vomiting after a single 1 mg semaglutide dose	Oral	Not disclosed in the announcement	Not disclosed in the announcement	Single semaglutide challenge; most vomiting occurred by day 2	Company-announced human clinical trial, not peer reviewed
Approved indication, prevention of motion-induced vomiting	Oral	See the FDA prescribing information	See the FDA prescribing information	See the FDA prescribing information	Regulatory label (not summarized here)

Only the Phase 2 study has a reported amount: 85 mg twice daily, given as pretreatment before a single 1 mg Wegovy injection, according to trade press coverage of Vanda’s announcement. The Phase 3 announcement did not state the tradipitant dose. No practitioner-reported, community-reported or vendor-reported dosing for GLP-1-related vomiting was identified, and no established or reliably sourced dosing information was identified beyond the Phase 2 figure. Both studies used one high semaglutide dose, so they do not describe how tradipitant would be used alongside a normal gradual dose increase. The amounts in the table are trial amounts, not a recommended regimen.

Side effects, risks, and limitations

Vanda describes NEREUS as generally well tolerated in the Phase 3 study, with a safety profile consistent with earlier studies and no new safety signals. The announcement did not include an adverse-event table, so the rates of individual side effects in the GLP-1 setting cannot be stated. The prescribing information for the approved motion-sickness use is the source for known adverse reactions.

Other limits: the results have not appeared in a peer-reviewed journal; the high-burden vomiting analyses were post hoc; the studies were short and used a single challenge dose; only semaglutide was tested; and interactions with GLP-1 medicines in everyday use have not been described in the sources reviewed. Adding a second prescription also raises questions of cost and access that the trials did not address.

Regulatory and developmental status

United States: approved by the FDA in December 2025 for the prevention of vomiting induced by motion in adults. It is not approved for GLP-1-related vomiting. After the Phase 3 results, Vanda said it plans to discuss them with the FDA and to submit a supplemental new drug application; the company has described the FDA discussion as taking place in 2027. Status in other countries was not established in the sources reviewed.

Frequently asked questions

What is tradipitant?

An oral NK-1 receptor antagonist, sold as NEREUS, that is FDA approved for preventing motion-induced vomiting and is being studied for vomiting caused by GLP-1 medicines. It is not a peptide.

Does tradipitant work for GLP-1 nausea and vomiting?

In a Phase 3 trial, fewer people vomited on tradipitant (43.0%) than on placebo (58.5%) after a single 1 mg dose of semaglutide. These are company-announced results that have not been published in a journal, and they apply to that specific dosing design.

What dosage has been studied?

The Phase 2 study used 85 mg twice daily as pretreatment, per trade press coverage. The Phase 3 dose was not disclosed in the announcement. These are trial amounts, not a recommended regimen.

Is tradipitant approved?

It is FDA approved only for preventing motion-induced vomiting. It is not approved for vomiting caused by GLP-1 medicines.

Does it help people stay on GLP-1 medicines?

That has not been tested. The trials measured vomiting over a short window and did not measure persistence, weight loss or outcomes over months.

Is it a peptide?

No. Tradipitant is a small synthetic molecule. It is covered here because of its connection to GLP-1 medicines.

What remains unknown?

The Phase 3 dose, the full side-effect data, results with gradual semaglutide titration, results with tirzepatide and other agents, and whether the effect improves treatment persistence.

Bottom line

Tradipitant is a small-molecule NK-1 blocker with an approved motion-sickness use and a new, company-announced Phase 3 signal against vomiting after a single high dose of semaglutide. The strongest evidence is two randomized placebo-controlled human trials, both announced by the developer rather than published. The only reported dose is the Phase 2 amount, and no community-reported dosing was identified. Whether it helps people stay on GLP-1 treatment, and how it performs under normal dose escalation, remains unknown. Related: orforglipron, retatrutide, eloralintide. Plain-English news coverage is on The Weight Loss Atlas.