Future Opportunities for Potassium Competitive Acid Blocker in Gastroesophageal Reflux Disease and Beyond

Background: Potassium-competitive acid blockers (P-CABs) are a novel class of acid-suppressive agents with unique pharmacologic properties, including rapid onset of action, prolonged acid suppression, and predominantly CYP3A4 metabolism. While currently approved for select indications, such as Helicobacter pylori eradication, erosive esophagitis, and nonerosive reflux disease, emerging clinical data suggest broader therapeutic potential. The aim of this review is to identify clinical opportunities for PCABs that are based on their pharmacokinetics and pharmacodynamics characteristics. Methods: This narrative review evaluated data from clinical trials and observational studies to assess the future opportunities of P-CABs in the management of gastroesophageal reflux disease (GERD) and other conditions. Articles were selected based on relevance, design, and novelty. Results: The evidence demonstrates that P-CABs represent a promising advancement in acid-suppressive therapy, offering profound, fast-acting, and sustained acid suppression. Their pharmacologic properties enable addressing unmet needs in acid and non acid-peptic disorders. These include but not limited to refractory GERD, functional dyspepsia, GERD after sleeve gastrectomy, and GERD following POEM. Additionally, P-CABs may offer a superior diagnostic utility compared to PPIs as a P-CAB test. Early findings indicate possible roles for P-CABs in the management of Barrett’s esophagus, reflux hypersensitivity, eosinophilic esophagitis, nighttime GERD, extraesophageal manifestations of GERD, and as a non-continuous GERD treatment strategy. Conclusions: P-CABs are poised to expand their role beyond current indications. Their pharmacologic profile and accumulating clinical evidence position them as promising agents for many areas of unmet need in GERD as well as other disorders like functional dyspepsia, reflux hypersensitivity and eosinophilic esophagitis.