Acid Suppression and Pancreatitis: Are PCABs Safer Than PPIs? A Global Database Analysis

This study aimed to evaluate the incidence of acute pancreatitis (AP) following initiation of potassium-competitive acid blockers (PCABs) versus proton pump inhibitors (PPIs).

The comparative risk of AP associated with PCABs versus PPIs remains uncertain.

This retrospective cohort study analyzed data from the TriNetX database, which included adult patients who received a prescription for either PCAB or PPI between January 1, 2016, and August 1, 2025. Patients with a prior diagnosis of acute or chronic pancreatitis, pancreatic neoplasms, organ transplantation, or pregnancy were excluded. Propensity score matching (1:1) was used to adjust for demographic and other confounders. Univariate Cox proportional hazards models were used to assess the incidence of AP within 90 days of therapy initiation.

In total, 77,841 adults using PCAB and 13,497,134 adults using PPI were included. Among them, 80 patients in the PCAB cohort and 96,170 patients in the PPI cohort developed AP. The overall incidence of AP within 90 days of therapy initiation was 0.65% in the PCAB cohort and 0.96% in the PPI cohort, with the highest rates observed in adults aged 75 years or older and females. After matching, PCAB use was not associated with a statistically significant difference in new-onset AP compared with PPI (OR: 0.624; P=0.24). PCAB users had significantly lower odds of acute respiratory failure, acute renal failure, and sepsis than PPI users. Mortality was also significantly lower in the PCAB cohort.

The study suggests that PCABs may offer a safer alternative to PPIs with respect to AP risk, although further investigation is warranted.