Association between Use of Oral Anti-Diabetic Drugs and the Risk of Sepsis: A Nested Case-Control Study

Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan's National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77-0.83, P < 0.001), but meglitinide (adjusted OR 1.32, 95% CI 1.25-1.40, P < 0.001) use was associated with the increased risk of developing sepsis. The risk for development of sepsis was also lower among current (adjusted OR 0.87, 95% CI 0.78-0.96) and recent (adjusted OR 0.83, 95% CI 0.73-0.94) thiazolidinedione users. Current or recent sulfonylurea use and dipeptidyl peptidase-4 inhibitor use were not significantly associated with the development of sepsis. Our results highlight the need to consider the potential pleiotropic effect of OADs against sepsis in addition to the lowering of blood glucose.