Metopimazine in Gastroparesis: Safe, Mixed Efficacy Signals- AJG Feb.2026

Gastroparesis is a chronic, debilitating disorder characterised by nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Current pharmacologic options are limited by modest efficacy and safety concerns, particularly central nervous system and cardiac adverse effects. There is therefore a strong need for new, well-tolerated therapies that effectively target core symptoms—especially nausea.

Metopimazine is a dopamine D2 receptor antagonist that is peripherally restricted, reducing the risk of central neurologic side effects. It has been used in Europe for decades to treat nausea and vomiting. This phase 2 study evaluated NG101, an oral mesylate formulation of metopimazine, for the treatment of gastroparesis.

In this multicenter, double-blind trial, patients with diabetic or idiopathic gastroparesis received NG101 at varying doses or placebo for 12 weeks. Symptom severity was tracked using daily patient-reported outcome diaries, with a primary focus on nausea severity and multiple secondary assessments of global symptom improvement.

Although NG101 did not significantly reduce nausea severity compared with placebo on the primary symptom score, patients receiving NG101 consistently reported greater overall improvement in nausea when asked to rate their global change in symptoms. This suggests that patients perceived meaningful benefit, even if the magnitude of symptom change on numeric scales was modest. Importantly, NG101 was well tolerated, with a favorable safety profile across all doses.

Notably, treatment effects appeared more favorable in idiopathic gastroparesis than in diabetic gastroparesis, raising the possibility of phenotype-specific benefit. This finding aligns with emerging evidence that gastroparesis subtypes respond differently to pharmacologic therapies.

In summary, while NG101 did not meet its primary efficacy endpoint, it demonstrated good tolerability and encouraging patient-reported improvements, particularly in idiopathic gastroparesis. These results support further targeted studies to clarify its role in symptom-directed management of gastroparesis.