Fexuprazan and Esomeprazole in Gastroesophageal Reflux Disease: A Comprehensive Review of Therapeutic Efficacy, Safety and Patient Reported Outcome

Background: Gastroesophageal Reflux Disease (GERD) is a prevalent gastrointestinal disorder that considerably affect patient’s quality of life, sleep disturbance and increased healthcare burden. Proton pump inhibitor (PPI), particularly Esomeprazole is used as a first line treatment in GERD, however, due to its limitation such as delayed onset of action, inadequate nocturnal symptom relief a newer development of acid- suppressive agent has been encouraged. Fexuprazan, a potassium competitive acid blocker (P-CAB) has emerged as a promising alternative for the treatment of GERD. This review compares the effectiveness and therapeutic outcome of Esomeprazole and Fexuprazan in the management of GERD.  Objective: To review and compare the available reports on the therapeutic effectiveness, safety, nocturnal symptom relief and improvement in quality of life of Esomeprazole and Fexuprazan in the management of Gastroesophageal reflux disease (GERD).  Main Finding: Literature from PubMed, Scopus, Google Scholar and Embase publishes between 2010 and 2026 was reviewed. The reviewed evidence indicated that Fexuprazan demonstrate comparable efficacy to Esomeprazole in the management of Erosive esophagitis (EE) and relieving GERD. Several clinical trials and recent meta-analysis have also that Fexuprazan shows comparable safety profile to that of Esomeprazole. Furthermore, Fexuprazan has demonstrated more rapid acid suppression than conventional PPIs in randomized clinical trials, superior control over nocturnal symptoms and significant improvement in Quality of life in patients reported outcome like GERD-Q, GERD-HRQoL, QOLRAD. Both medications were well tolerated with similar incident of treatment-emergent adverse events.  Conclusion: Current evidence shows that Fexuprazan is a promising alternative to Esomeprazole in the treatment of GERD, especially in patients requiring rapid acid control or those experiencing severe nocturnal symptoms. Though existing studies support Fexuprazan comparable efficacy and safety profile, long-term studies are required to assess the maintenance therapy, recurrence of symptom after discontinuation of therapy and effectiveness of the treatment in patients diagnosed with Non-erosive reflux disease (NERD).