S1133 Vonoprazan for Functional Dyspepsia: Systematic Review and Meta-Analysis

Introduction: Potassium-competitive acid blockers (P-CABs), such as vonoprazan, offer more potent and rapid acid suppression than proton pump inhibitors and are effective in treating acid-related organic disorders. However, their overall impact on symptoms of functional dyspepsia (FD) has not been well quantified. Methods: On 15 May 2025, We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science using search terms such as ((functional dyspepsia) OR “Dyspepsia”[Mesh]) AND (vonoprazan)). Eligible cross-sectional and longitudinal studies evaluating the effect of vonoprazan on functional dyspepsia were included. Post-treatment Global Overall Symptom Scale (GOSS) means and, where available, epigastric pain scores were pooled using inverse-variance random-effects meta-analysis. Heterogeneity was assessed using the I² and τ² statistics. A leave-one-out approach was used to assess the robustness of the findings. Results: Our search returned 91 papers (Cochrane-9, PubMed-9, Embase-52, Web of Science-21). After screening for duplication and full-text review, only 3 studies met our eligibility criteria: 1 double-blind randomized controlled trial from Thailand (n = 60) and 2 Japanese observational cohorts (n = 43, n = 48), yielding data on 151 participants. Global symptom relief, assessed with the Global Overall Symptom Scale (GOSS), showed a pooled mean difference of 5.72 (95% CI 5.29–6.14), although heterogeneity was high (I² = 98.8%, P = 0.0001). For epigastric pain, the 2 contributing studies (n = 108) reported post-treatment means of 1.67 ± 0.80 and 1.63 ± 0.84; the pooled estimate was 1.65 (95% CI 1.50–1.81) with no heterogeneity (I² = 0%, P = 0.80). Safety analysis covering 179 patient-months of vonoprazan exposure revealed no serious drug-related adverse events. The most frequent mild events were bloating (7%), nausea (5%), and constipation (3%). Conclusion: Vonoprazan appears to lessen epigastric pain and improve overall symptom burden in functional dyspepsia, with no serious safety signals detected in the available evidence. This assessment is limited by the small sample size, marked heterogeneity among the 3 eligible studies, and the absence of direct comparisons with placebo or proton pump inhibitors. Larger, multicenter, placebo- and proton pump inhibitor-controlled trials, stratified by FD subtype, are needed to confirm efficacy.