Vanda’s Tradipitant prevents GLP-1 induced nausea and vomiting

Vanda Pharmaceuticals has announced positive topline results from its randomised controlled clinical study (VP-VLY-686-2601) evaluating tradipitant, an oral neurokinin-1 (NK-1) receptor antagonist, for the prevention of nausea and vomiting induced by GLP-1 receptor agonist Wegovy in overweight and obese adults.

This study, which pre-treated patients with either tradipitant or placebo before administering a 1 mg injection of Wegovy, a dose that normally takes 9 weeks of titration to reach, succeeded and met its primary endpoint, with only 29.3% of tradipitant-treated participants (17/58) experiencing vomiting compared to 58.6% on placebo (34/58) (p=0.0016), representing a 50% relative reduction. The study also met the key secondary endpoint of the proportion of participants with vomiting and significant nausea at 22.4% in the tradipitant group (13/58) versus 48.3% on placebo (28/58) (p=0.0039, Table 1).

Tradipitant demonstrated a favorable safety profile consistent with previous studies with no new safety signals observed.

Table 1: Primary and secondary outcomes

Endpoint	Placebo (N=58)	Tradipitant (N=58)	P-value
Proportion with vomiting*	58.6% (34/58)	29.3% (17/58)	0.0016
Proportion with vomiting and worst nausea ≥3**	48.3% (28/58)	22.4% (13/58)	0.0039

Primary endpoint *Key secondary endpoint, nausea of >= 3 denotes moderate or worse on a 0-5 point scale of severity.

"These results demonstrate tradipitant's potential to mitigate GLP-1 induced nausea and vomiting which are key contributors of the 30-50% real-world discontinuation rates for GLP-1 agonists, often before therapeutic doses are reached," said Dr Mihael H Polymeropoulos, President, CEO and Chairman of Vanda. "Tradipitant's effect in reducing nausea and vomiting could significantly improve GLP-1 agonist adherence enabling more people to receive the full therapeutic benefit."

The observed efficacy is consistent with tradipitant's demonstrated performance in motion sickness in multiple studies, where it reduced vomiting by more than 50% in randomized studies with over 800 individuals. These results position tradipitant as a potentially transformative adjunct in the rapidly expanding global GLP-1 agonist market, which is currently greater than $50 billion through the first nine months of 2025.

Early discontinuations due to gastrointestinal side effects impose substantial costs on patients and payors. Patients forgo meaningful weight loss (15–20% with sustained use) and reductions in complications like diabetes progression and cardiovascular events, diminishing health outcomes. Payors face wasted spending on unused prescriptions without benefits, plus ongoing costs from unmanaged obesity, including hospitalisations.

The randomised, double-blind, placebo controlled trial studied 116 healthy overweight or obese adults (BMI 25–40 kg/m²) without prior GLP-1 agonist experience. Participants were injected with 1mg Wegovy, a dose that normally takes 9 weeks of titration to reach under current prescribing guidelines. Participants were pre-treated with tradipitant 85 mg twice daily or placebo for 1 week, followed by 1 week of continued treatment post-dosing. Outcomes were measured using daily patient-reported assessments.

Vanda will evaluate an efficient development path towards obtaining regulatory approval for this unmet need. A Phase III programme is anticipated to initiate in the first half of 2026, positioning tradipitant as a key adjunct to improve outcomes in GLP-1 agonist treatments.