An Overview of Clinical Data and Likely Mechanisms of New-Onset Diabetes Mellitus (NODM) Induced by Proton Pump Inhibitors (PPIs)

Background: Proton pump inhibitors (PPIs) and the prevalence of diabetes and hyperglycemia have been the subject of numerous publications in recent years. Objective: The clinical evidence of diabetes and hyperglycemia in patients taking PPIs for an extended period of time is the main topic of our current review. Methods: To find publications, including randomized controlled trials, observational cohort studies, systematic reviews, and meta-analyses, keywords such as diabetes mellitus, new-onset diabetes mellitus, drug-induced, proton pump inhibitors, PPI-induced, diabetogenic, and iatrogenic were used to search online databases like Medline/Pubmed/PMC, Scopus, Web of Science, Google Scholar, and reference lists. Results: Prolonged PPI therapy has been linked to New-onset Diabetes Mellitus (NODM), according to a number of prospective and retrospective observational studies, meta-analyses, and randomized controlled clinical trials. Conclusion: A number of mechanisms, including hypergastrinemia, gut dysbiosis, hypomagnesemia, decreased IGF-1 levels, and progesterone X receptor (PXR) activation, have been proposed to explain the development of NODM in relation to long-term PPI usage. The increased risk of NODM linked to long-term PPI usage should be known to clinicians, particularly gastroenterologists, and other prescribers, pharmacists, and other healthcare professionals.