Umbrella Review of 42 Systematic Reviews With Meta-analyses

The Safety of Proton Pump Inhibitors

Elizabeth M. Salvo; Nicole C. Ferko; Sarah B. Cash; Ailish Gonzalez; Peter J. Kahrilas


Aliment Pharmacol Ther. 2021;54(2):129-143. 

In This Article


This systematic umbrella review identified 42 recently published systematic reviews with meta-analyses which investigated associations between PPI use and adverse events. Significant associations were consistently reported for multiple adverse events spanning diverse organ systems, including bone fracture, kidney disease, C. difficile infection, pneumonia and gastric cancer. Although a causal relationship between PPI use and several safety outcomes, cannot be concluded due to the predominantly observational evidence base, the consistency of associations across many studies provides rationale for clinicians to carefully weigh the benefits vs potential risks of long-term PPI use for patients. However, higher quality evidence, specifically large randomised trials, are greatly needed to substantiate these findings.