Beyond acid inhibition: new therapies and innovative approaches

Peptic ulcer disease is no longer viewed as an exclusively “acid-dependent” condition. Although proton pump inhibitors (PPI) dominated therapy for decades, their limitations (genetic variability, rebound acid hypersecretion, and bacterial resistance) have driven a paradigm shift. Current management is now more comprehensive, combining acid control with mucosal restoration and effective Helicobacter pylori eradication. Potassium-competitive acid blockers (P-CAB), such as vonoprazan and tegoprazan, provide faster, more potent, and more predictable acid suppression than PPIs, achieving higher healing and eradication rates, even in resistant strains. In parallel, modern H. pylori regimens, including dual and quadruple P-CAB–based therapies, reach eradication rates close to 95%. Mucosal protective agents (rebamipide, sucralfate, misoprostol) are being re-emphasized, along with emerging regenerative therapies that promote epithelial repair. In addition, the gastric microbiota has gained recognition as a key factor, with probiotics and symbiotics improving tolerability, adherence, and clinical outcomes. The future points toward personalized medicine: pharmacogenomics, artificial intelligence, and regenerative strategies will enable more precise, effective, and sustainable treatments.