Safety of Potassium-Competitive Acid Blockers Compared With Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease and Peptic Ulcer Disease - A Systematic Review and Meta-Analysis

Sep 30, 2026

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Potassium-competitive acid blockers (P-CABs) are designed to provide rapid, sustained acid suppression, aiming to address limitations of proton pump inhibitors (PPIs). Safety evidence for P-CABs is limited, despite well-characterized PPI adverse events. This systematic review and meta-analysis compared P-CABs versus PPIs in gastroesophageal reflux disease and peptic ulcer disease, with hypergastrinemia assessed quantitatively alongside qualitative synthesis of adverse events.

LanguageEnglish

CategoryHealthcare

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Pages13

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Background and Aim

Methods

Results

Conclusions

Journal of Gastroenterology and Hepatology SYSTEMATIC REVIEW OPEN ACCESS Safety of Potassium-Competitive Acid Blockers Compared With Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease and Peptic Ulcer Disease: A Systematic Review and Meta-Analysis Yewon Jang1 | Jongho Park2 | Dahee Kang1 | Jae Hyun Kim3 | Hyuk Soon Choi4 | Ha-Lim Jeon3 | Hankil Lee5 1College of Pharmacy, Ajou University, Suwon, Republic of Korea | 2Department of BioHealth Regulatory Science, Graduate School of Ajou University, Suwon, Republic of Korea | 3School of Pharmacy and Institute of new Drug Development, Jeonbuk National University, Jeonju, Republic of Korea | 4Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea | 5College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea Correspondence: Ha-Lim Jeon ([hrjeon@jbnu.ac.kr](hrjeon@jbnu.ac.kr)) | Hankil Lee ([hankil@ewha.ac.kr](hankil@ewha.ac.kr)) Received: 22 May 2025 | Revised: 29 July 2025 | Accepted: 10 August 2025 Keywords: gastroesophageal reflux disease | meta-analysis | potassium-competitive acid blockers | proton pump inhibitors | systematic review ABSTRACT Background and Aim: Potassium-competitive acid blockers (P-CABs) are a novel class of acid suppressants developed to overcome the limitations of proton pump inhibitors (PPIs), providing rapid and sustained acid suppression. While PPI-related adverse events (AEs) are well-documented, safety data on P-CABs remain limited. This study systematically reviewed AEs of P-CABs compared with PPIs, with a meta-analysis focusing on hypergastrinemia. Methods: Following a preregistered PROSPERO protocol (CRD42024565011), we searched for randomized controlled trials (RCTs) and observational studies comparing P-CABs and PPIs in patients with gastroesophageal reflux disease or peptic ulcer disease. Frequently reported AEs and serious AEs (SAEs) were qualitatively synthesized; hypergastrinemia was quantitatively analyzed using a random-effects model. Results: Ten RCTs and one observational study were included. Nine studies reported specific AEs, with diarrhea reported in seven studies and constipation, nasopharyngitis, and liver-related events, each reported in three. Most AEs had reporting rates below 5%, except diarrhea, nasopharyngitis, and upper respiratory tract inflammation, which exceeded 5% in both groups. Fracture demonstrated the largest relative difference between the groups, with a threefold higher rate in the P-CAB group. SAEs were observed in fewer than 10% of patients in both groups in most studies. A meta-analysis of six studies showed greater serum gastrin elevation in the P-CAB group compared with the PPI group (mean difference: 130.92 pg/mL, 95% confidence intervals: 36.37–225.47) . Conclusions: P-CABs demonstrate a comparable AE risk to PPIs but monitoring for hypergastrinemia and hepatic dysfunction is essential. Further research is required to support safer clinical use. 1 | Introduction Gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) are among the most common gastrointestinal (GI) disorders worldwide, affecting millions of people and driving a significant increase in the use of acid-suppressant drugs [1, 2] . Acid suppressants, particularly proton pump inhibitors (PPIs), have been widely used for the treatment of these acid-related GI This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2025 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. 28 Journal of Gastroenterology and Hepatology, 2026; 41:28–40 [https://doi.org/10.1111/jgh.70178](https://doi.org/10.1111/jgh.7

FAQs

What was the primary objective of this systematic review?

To systematically review adverse events of P-CABs compared with PPIs in patients with gastroesophageal reflux disease and peptic ulcer disease, using meta-analysis to focus on hypergastrinemia.

Which studies and patient populations were included?

Randomized controlled trials and observational studies comparing P-CABs and PPIs in patients with gastroesophageal reflux disease or peptic ulcer disease.

How did adverse event risks compare between P-CABs and PPIs?

Overall, most adverse events had reporting rates below 5% in both groups, while diarrhea, nasopharyngitis, and upper respiratory tract inflammation exceeded 5% in both groups; fracture showed the largest relative difference with a higher rate in the P-CAB group.

Sep 30, 2026

Uploaded by Himbo