S3141 Comparative Efficacy of Pharmacologic Therapies for Gastroparesis: A Systematic Review and Network Meta-Analysis

Introduction: Gastroparesis is a chronic motility disorder with limited pharmacological options. Despite the availability of prokinetics, antiemetics, and investigational agents, clinical efficacy remains uncertain owing to limited head-to-head comparisons. We conducted a network meta-analysis to evaluate and rank the efficacy of pharmacological therapies for gastroparesis. Methods: We systematically searched PubMed, Embase, and CENTRAL from January 1985 to present for randomized controlled trials evaluating adult patients with gastroparesis treated with pharmacologic agents. Interventions included prucalopride, cisapride, revexepride, metoclopramide, relamorelin, TZP-102, aprepitant, tradipitant, cannabidiol (CBD), and domperidone. The primary outcomes were symptomatic improvement, reported as standardized mean differences (SMDs) from validated symptom scores, and changes in gastric half-emptying time (t½). A Bayesian network meta-analysis was performed using a common effects model. Treatments were ranked by efficacy using the Surface Under the Cumulative Ranking curve (SUCRA) values. Results: A total of 21 trials comprising 2,452 patients were included in the study. For symptom improvement, 19 studies that compared 10 treatments contributed to the network. Cisapride (SMD 1.88; 95% confidence interval [CI] -2.71 to -1.06; SUCRA = 0.98), relamorelin (SMD 1.15; 95% CI -2.15 to -0.16; SUCRA = 0.86), and aprepitant (SMD 0.60; 95% CI -0.88 to -0.32; SUCRA = 0.76) significantly outperformed the placebo. TZP-102, prucalopride, and tradipitant showed modest benefits, whereas domperidone, metoclopramide, CBD, and revexepride had limited or non-significant effects. For gastric emptying improvement, 12 studies assessed 7 agents. Prucalopride demonstrated the most pronounced effect (mean difference [MD] -46.00 min; 95% CI -55.54 to -36.46; SUCRA = 0.98), followed by cisapride (MD -35.88 min; 95% CI -47.36 to -24.41; SUCRA = 0.85) and relamorelin (MD -10.35 min; 95% CI -17.29 to -3.41; SUCRA = 0.59). Other agents, including metoclopramide, revexepride, CBD, and TZP-102, showed no significant changes compared with placebo. Conclusion: Cisapride, relamorelin, and aprepitant demonstrated the highest efficacy for symptom relief, whereas prucalopride and cisapride were most effective in accelerating gastric emptying. The disconnection between symptomatic and motility-based outcomes highlights the need for individualized treatment selection and development of more robust surrogate endpoints in future gastroparesis trials.