Effectiveness and safety of drugs for the treatment of gastroparesis: evidence-based medicine data. Review

Abstract

Gastroparesis is a motility disorder of the upper gastrointestinal tract, characterized by delayed emptying of the stomach from solid substances, in the absence of any mechanical signs of obstruction of the stomach or duodenum. The etiology of gastroparesis is heterogeneous, but there are three well‑known subtypes: diabetic, iatrogenic, resulting from upper gastrointestinal surgery or medication, and idiopathic gastroparesis. Despite recently updated guidelines for the management of patients with gastroparesis, this condition remains difficult to diagnose and treat. A recent systematic review and network meta‑analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of all drugs tested in patients with gastroparesis. The only FDA‑approved drug is metoclopramide, a dopamine D2 antagonist and weak 5‑HT4 agonist, which in gastroparesis is approved for a maximum of three months of treatment due to endocrine, cardiac, and neurologic side effects. The results of the conducted meta‑analysis confirmed the effectiveness of dopamine antagonists in gastroparesis. Domperidone has been the subject of a warning due to an increased risk of QT prolongation on the electrocardiogram, but pharmacoepidemiological data suggest that this is rare, and ventricular arrhythmia occurs only in 0.02% of patients treated with the drug. A meta‑analysis suggested that clebopride, another dopamine antagonist, is an effective drug for gastroparesis, ranking first among effects on global symptoms, although this was shown in only one RCT, and the drug is not yet available in many countries, including the USA. The tachykinin‑1 antagonists aprepitant and tradipitant ranked third and fifth, respectively, for effects on global symptoms of gastroparesis, but when examined for effects on global symptoms according to drug class, they ranked second. Although 5‑HT4 agonists have not been shown to be sufficiently effective, trials of velosetrag are ongoing, and prucalopride was superior to placebo in a one cross‑over study included in the meta‑analysis.