Are proton-pump inhibitors associated with development of diabetes?

In a recent observational study, prolonged use of proton-pump inhibitors (PPIs) was associated with the development of diabetes. A case-control study from a National Health Service database in Italy addresses the same issue.

Fifty thousand adults (age≥40) who developed diabetes during a 5-year interval were compared with 50,000 people without diabetes, matched on age, sex, and an elaborate clinical status score. In analyses adjusted for numerous potentially confounding variables, researchers detected a significant relation between exposure to a PPI and a new diagnosis of diabetes.

Diabetes has become yet another condition associated with PPI use, but cause and effect remain unproven — as is the case with so many possible associations between PPIs and adverse effects. One reason not to ignore these findings is that a possible causal explanation has been proposed: Chronic acid suppression changes the gut microbiome, and changes in the gut microbiome have been associated with abnormal glucose metabolism.

For now, it might be reasonable to use these findings as the impetus to deprescribe PPIs in patients with prediabetes who use these drugs but have no compelling indication for them.