Dose-Dependent Proton Pump Inhibitor Exposure and Risk of Type 2 Diabetes: A Nationwide Nested Case–Control Study

Background: To investigate the association between proton pump inhibitor (PPI) exposure and a risk of type 2 diabetes mellitus (T2DM) among patients with upper gastrointestinal disease (UGID). Method: We conducted a case–control study from Taiwan’s National Health Insurance Research Database between 1998 and 2013. A total of 20,940 patients with T2DM and 20,940 controls were included. The dose of PPIs was categorized according to the cumulative defined daily dose (cDDD). The risk of T2DM was assessed using conditional logistic regression analysis. Result: Compared with cDDD ≤ 30, higher dosage of PPI exposure was associated with an increased risk of T2DM development: cDDD 31–120 (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.13–1.26); cDDD 121–365 (OR: 1.26, 95% CI: 1.19–1.33); and cDDD > 365 (OR: 1.34, 95% CI: 1.23–1.46). Subgroup analysis of individual PPI showed that pantoprazole (OR: 1.14, 95% CI: 1.07–1.21), lansoprazole (OR: 1.08, 95% CI: 1.03–1.12), and omeprazole (OR: 1.11, 95% CI: 1.06–1.16) have a significantly higher risk of T2DM development. Conclusions: A dose-dependent increased risk of T2DM was found among patients with UGID using higher doses of PPIs compared with those with lower doses of these drugs. Further studies are necessary to investigate the underlying pathophysiology of PPIs and T2DM.