Nereus, an oral antiemetic, reduces semaglutide-related vomiting in phase 3 trial

Clinical takeaway: Nereus may offer a future option for reducing GLP-1-related vomiting, a potential barrier to continued treatment. Although approved for motion-induced vomiting, it remains investigational for this use.

Gastrointestinal adverse effects can make it difficult for patients to continue GLP-1 receptor agonist therapy. Vanda Pharmaceuticals has reported positive phase 3 results for Nereus (tradipitant), an oral neurokinin-1 (NK-1) receptor antagonist evaluated for preventing semaglutide-related vomiting.

Nereus was first FDA-approved in 2025 to prevent motion-induced vomiting in adults. It blocks signals involved in the vomiting reflex.

In the randomized, placebo-controlled trial, participants received a single 1 mg dose of semaglutide without the gradual dose escalation used in clinical practice. This approach was intended to test the drug under conditions likely to cause vomiting.

Vomiting occurred in 43.0% of participants receiving Nereus versus 58.5% receiving placebo—a 15.5-percentage-point absolute reduction and a 27% relative reduction. The proportion experiencing both vomiting and severe nausea was also significantly lower with Nereus: 33.1% versus 50.6%.

Post hoc analyses suggested reductions in more burdensome vomiting patterns. Frequent multiday vomiting, defined as more than two vomiting episodes on each of at least two days, occurred in 6.3% of participants receiving Nereus versus 15.9% receiving placebo, a 60% relative reduction. Extreme vomiting, defined as more than ten total episodes, occurred in 2.8% versus 14.6%, an 81% relative reduction.

Most vomiting occurred within the first two days after semaglutide administration. Vanda reported that Nereus was generally well tolerated, with no new safety signals.

Based on results from its phase 2 and phase 3 programs, Vanda plans to discuss the findings with the FDA and seek approval to prevent vomiting associated with GLP-1 receptor agonist therapy.

“These results demonstrate that Nereus can meaningfully reduce vomiting and frequent multi-day vomiting induced by GLP-1 therapy, which are key contributors to treatment discontinuation,” said Mihael H. Polymeropoulos, MD, Vanda’s president and CEO.

Source: Vanda Pharmaceuticals Inc. (2026 Oct 27). Vanda Pharmaceuticals announces positive results from Study 3601 of NEREUS™ (tradipitant) for prevention of GLP-1-induced vomiting