Results, presented at ObesityWeek® 2025, showed patients receiving NG101 saw 40% reduction in nausea incidence and 67% reduction in vomiting incidence
Only 30% of patients who start GLP-1s for weight loss are still using them after one year, with GI side effects cited as the #1 cause of treatment discontinuation
NG101 is a first-in-class therapy being evaluated for GLP-1-induced nausea and vomiting, the source of billions of dollars in annual lost revenues
WOBURN, Mass., Nov. 07, 2025 (GLOBE NEWSWIRE) -- Neurogastrx, Inc., today presented proof-of-concept data from its placebo-controlled Phase 2 clinical study of NG101 (metopimazine mesylate), an oral, peripherally restricted dopamine D2 receptor antagonist for the treatment of GLP-1-induced nausea and vomiting. These data, shared in an oral presentation at ObesityWeek® 2025, demonstrated that NG101 significantly reduced the incidence, duration, and severity of nausea and vomiting associated with the use of a GLP-1 agonist.
“GLP-1 agonists can be life-changing for individuals with obesity. Yet for so many, the common GI side effects of nausea and vomiting are often unbearable, leading to patients discontinuing treatment or being unable to reach optimal doses,” said Sean Wharton, MD, PharmD, Medical Director, Wharton Medical Clinic for Weight and Diabetes Management, Ontario, Canada, and an adjunct professor at both McMaster University in Hamilton and York University in Toronto. “An oral treatment such as NG101 may make GLP-1 receptor agonists tolerable for many patients.”
Key Results from Clinical Study of NG101 for Semaglutide-Induced Nausea and Vomiting
In the study, a total of 90 participants aged 18-55 received a single subcutaneous dose of semaglutide (0.5 mg), along with five days of NG101 20 mg twice per day (BID) or placebo. The study evaluated the efficacy of NG101 in reducing the incidence, duration, and severity of nausea and vomiting. Key clinical study results showed that, compared to placebo, NG101 significantly:
- Reduced the incidence of nausea by 40% (p=0.0203)
- Decreased the incidence of vomiting by 67% (p=0.0274) and the number of discrete vomiting episodes by 56% (p=0.0238)
- Reduced the duration of nausea and vomiting (p=0.0063); events lasting more than one day occurred in 22% vs. 51% of participants with NG101 vs. placebo
- Decreased nausea severity by 70% (p=0.0138) as reported by the participant
Among participants who received NG101 vs. placebo, there were also substantially fewer adverse events, resulting in an improved safety profile when semaglutide is co-administered with NG101.
Participant-reported outcomes (PROs) in the study revealed a greater symptom burden of nausea and vomiting than clinical assessments suggested. Clinicians graded less than five incidents of nausea and vomiting as moderate or severe, while 70 patients graded themselves as having moderate or severe symptoms at any time (n=90). PROs showed that NG101 reduced the maximum nausea rating of moderate-severe nausea by 31% (p=0.0225). The U.S. Food and Drug Administration (FDA) prioritizes the PRO measure for nausea and vomiting as it more accurately reflects the participant experience.
“Nausea and vomiting associated with GLP-1s prevent millions of patients globally from fully realizing the benefits of this transformative class of medicines,” said Jim O’Mara, president and CEO of Neurogastrx. “The real-world incidence of nausea and vomiting reported by patients is far more significant and disruptive than the investigator-reported events in clinical trials. The significant reductions in nausea and vomiting that we’re seeing with NG101, combined with a clean safety profile, support its future clinical development and evaluation with multiple GLP-1 treatments. Individuals who are taking GLP-1s for weight loss deserve to have access to sustainable and tolerable treatments.”
A study published in JAMA Network Open in January showed the one-year discontinuation rate of GLP-1 receptor agonists (liraglutide, semaglutide, or tirzepatide) for patients without type 2 diabetes was 64.8%, with GI events being the most frequent reason cited.1 “With the global GLP-1 market estimated at $63 billion in 2025, the sector is losing significant numbers of patients due to nausea and vomiting — and, more importantly, these patients are missing out on the clear benefits of weight loss on overall health, including metabolic and cardiovascular diseases associated with obesity.”
About NG101
NG101 is an oral, small molecule peripherally acting dopamine D2 receptor antagonist. Neurogastrx recently completed a proof-of-concept safety and efficacy study of NG101 in nausea and vomiting associated with glucagon-like peptide 1 (GLP-1) agonists. GLP-1 agonists primarily activate two areas in the brain. Activation of the Nucleus of the Tractus Solitarius (NTS) causes satiety (leading to weight loss) whereas activation of the Area Postrema (AP) causes nausea and vomiting. The NTS resides inside the brain and is therefore not accessible to NG101. By contrast, the AP is located outside the blood-brain barrier and represents an ideal target for NG101. The AP is rich in dopamine D2 receptors. By selectively targeting the AP and blocking D2 receptors, NG101 blocks the symptoms of nausea and vomiting triggered by GLP-1 agonists.
Details on the Phase 2 clinical study design can be found on www.clinicaltrials.gov (NCT06500429).
About Neurogastrx, Inc.
Neurogastrx, Inc. is a privately held specialty pharmaceutical company developing transformative therapies to advance the treatment of GI disorders for which meaningful therapeutic innovation is required to satisfy unmet patient need and disease burden.
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Amanda Breeding
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1 JAMA Netw Open. 2025 Jan 31;8(1):e2457349.
