“Chronic Exposure to Proton Pump Inhibitor use and Diabetes Mellitus Incidence. A Systemic Review and Meta-Analysis “

Abstract Proton pump inhibitors are very commonly prescribed drugs for gastrointestinal disorders. It is estimated that worldwide a total of 537 million adult populations are affected by diabetes mellitus. The present systematic review was planned to explore an association between PPIs use and the risk of DM occurrence which is unclear yet. We have performed a comprehensive literature search in popular electronic databases such as Pub Med, Embase, Scopus, Cochrane Library and ClinicalTrials.gov using a comprehensive search strategy from inception to December 2022. Quality analysis was assessed using the Newcastle-Ottawa scale system. All Statistical analyses were performed using the “Review Manager 5.4” version. The P value < .05 was set as statistically highly significant. This systematic review identified 12 studies (8: observational; 1: RCT & 3: case-control; n = 11, 64816) with a total of 1, 25,504 cases of diabetes incidence, and the median age ranged from > 18-74.9 years. The pooled RR findings have shown that exposure to PPIs is significantly associated with an increased risk of DM occurrence (RR, 2.44; 95% CI, 1.31–4.54) with high heterogeneity (I2 = 99%, P < 0.00001). A significant relationship between the chronic use of PPIs and the development of diabetes mellitus was found. Hypergastrenemia, gut dysbiosis, hypomagnesaemia, decrease pancreatic secretions, PXR activation, decrease in the levels of insulin-like growth factor-1 and low potency are some of the mechanisms proposed to explain an association of diabetes incidence with chronic PPI use. Furthermore, RCTs on PPIs associated risk of diabetes incidence are suggested