Comparing Proton Pump Inhibitors and Emerging Acid-Suppressive Therapies in Gastroesophageal Reflux Disease: A Systematic Review.

This systematic review evaluates the comparative efficacy and safety of proton pump inhibitors (PPIs) versus alternative acid-suppressive strategies in the treatment of gastroesophageal reflux disease (GERD). A comprehensive search was conducted across PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL), yielding 877 records, of which five randomized controlled trials met the inclusion criteria. These studies examined the effectiveness of newer agents such as potassium-competitive acid blockers (P-CABs), including vonoprazan, fexuprazan, and tegoprazan, as well as the use of mucosal protective agents and varied PPI administration strategies (on-demand vs. continuous). Findings indicated that P-CABs are noninferior or superior to PPIs in terms of symptom relief and mucosal healing, with tegoprazan demonstrating faster symptom control. Long-term use of vonoprazan was associated with higher gastrin levels and histological changes, although no malignant outcomes were reported. The addition of mucosal protective agents to PPI therapy enhanced histological remission and symptom control. On-demand PPI use showed similar outcomes to continuous use, suggesting it may be a viable option for certain patient populations. Overall, the review supports the growing role of individualized and alternative pharmacologic approaches in the effective management of GERD.