Educational guide
Novel drug may reduce nausea, vomiting during GLP-1 therapy
Novel drug may reduce nausea, vomiting during GLP-1 therapy Key takeaways: - Adults taking NG101 had fewer semaglutide-induced events of nausea and vomiting than those receiving placebo. - Fewer adverse events were reported with NG101 compared with placebo. AT
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Novel drug may reduce nausea, vomiting during GLP-1 therapy
Key takeaways:
- Adults taking NG101 had fewer semaglutide-induced events of nausea and vomiting than those receiving placebo.
- Fewer adverse events were reported with NG101 compared with placebo.
ATLANTA — An oral small molecule drug may reduce gastrointestinal adverse events for adults using a GLP-1-based obesity drug, according to data from a proof-of-concept study presented at ObesityWeek.
NG101 (Neurogastrx) is a peripherally acting dopamine D2 receptor antagonist designed to reduce nausea and vomiting, according to Kimberly Cummings, PhD, RAC, senior vice president of regulatory affairs and clinical development for Neurogastrx. Cummings said the agent targets the area postrema, a portion of the brain that controls nausea, and is a P-glycoprotein substrate, which limits the medication’s ability to cross the blood-brain barrier and impact the central nervous system.
Cummings said NG101 was developed to address the need to reduce gastrointestinal adverse events with incretin-based obesity drugs, as these types of adverse events are leading to drug discontinuation for patients.
“We know that there are some recommendations from physicians on how to manage these gastrointestinal effects, things like nutritional support [and] over-the-counter antiemetics, yet it’s not enough,” Cummings said. “We also learned this week that there are new GLP-1s being developed, new orals and new injectables, yet there’s still a gastrointestinal tolerability issue.”
In a randomized, double-blind, proof-of-concept trial, 90 healthy adults aged 18 to 55 years with a BMI between 22 kg/m2 and 35 kg/m2 who were not using a GLP-1 at enrollment were randomly assigned to 20 mg NG101 or placebo twice per day for 5 days. Both groups received a single, 0.5 mg dose of semaglutide (Wegovy, Novo Nordisk) on day 2. Researchers assessed the incidence, duration and severity of nausea and vomiting as key endpoints.
Adults receiving NG101 experienced 40% less nausea (P = .0203) and 67% less vomiting (P = .0274) than those receiving placebo. The NG101 group also had 70% less moderate to severe nausea vs. placebo (P = .0138). Of those who experienced nausea or vomiting, the duration was shorter, with events lasting more than 1 day among 22% of NG101 participants vs. 51% of adults receiving placebo. NG101 was also tied to a 56% reduction in discrete vomiting episodes compared with placebo (P = .0238).
A higher percentage of adults in the placebo group reported a GLP-1-related adverse event (78% vs. 62%) and drug-related adverse event (67% vs. 47%) than those receiving NG101. No serious adverse events or adverse events leading to treatment discontinuation were reported.
Cummings said the study had a short duration, and weight-related outcomes were not assessed. However, data from the STEP trials assessing semaglutide and the SURMOUNT trials examining tirzepatide (Zepbound, Eli Lilly) found both drugs conferred weight loss, regardless of nausea and vomiting adverse events.
“I think [NG101] does elucidate a potential pathway to demonstrate that we can improve the tolerability of the GLP-1s without impacting their efficacy, and hopefully there are additional studies for NG101 to come,” Cummings said.