Abstract
Gastroesophageal reflux disease (GERD) is a chronic relapsing disorder often inadequately controlled with proton pump inhibitors (PPIs), particularly in patients with nocturnal acid breakthrough (NAB) or non-erosive reflux disease (NERD). Tegoprazan, a potassium-competitive acid blocker (PCAB), offers rapid, potent, and CYP2C19-independent acid suppression. This systematic review and meta-analysis evaluated randomized controlled trials comparing Tegoprazan with PPIs in adults with GERD and related disorders. Databases searched included PubMed, Cochrane, Wiley, and ClinicalTrials.gov (2015-2026). Eighteen studies met inclusion criteria. In erosive esophagitis, Tegoprazan 50 mg once daily achieved mucosal healing rates of 91.1%-99.1%, non-inferior to PPIs (93.5%-98.9%; pooled RR = 1.01, 95% CI 0.98-1.05). Pharmacodynamic and clinical studies demonstrated faster acid suppression and improved nocturnal pH control versus PPIs, achieving pH ≥ 4 within 30-60 min and maintaining levels throughout the 12-h period. In nocturnal symptom analyses, Tegoprazan achieved earlier relief (1.5 vs. 3 days to first heartburn-free night) and higher proportions of heartburn-free nights (57.8% vs. 43.1%), with significantly greater complete (p = 0.038) and partial (p = 0.034) nighttime symptom resolution than Esomeprazole. In NERD, symptom resolution ranged from 42.5% to 48.9% versus 24.2% with placebo. In open-label functional dyspepsia cohorts, improvements ranged from 74.6% to 86.7% in open-label cohorts. Seven trials (n = 2492) showed higher Helicobacter pylori eradication with Tegoprazan-based therapy (RR = 1.05, 95% CI 1.01-1.09; p = 0.006; I (2) = 0%). Adverse events were mild and comparable to PPIs. Tegoprazan provides rapid, sustained acid suppression, effective nocturnal symptom control, and a modest but statistically significant improvement in H. pylori eradication, representing a potential alternative to PPIs for patients with persistent or CYP2C19-related variable response.