Abstract
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.
Highlights
Between 1980 and 2008, the number of people with type 2 diabetes (T2D) worldwide increased from approximately 150 million to 350 million[1]
To investigate whether susceptibility to sepsis differed among patients with T2D taking different classes of oral antidiabetic drugs (OADs), we used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a nationwide nested case-control study that controlled for the effects of predisposing the host factors to sepsis
We found that metformin use was associated with about 20% reduced risk of sepsis compared with nonuse
Summary
Between 1980 and 2008, the number of people with type 2 diabetes (T2D) worldwide increased from approximately 150 million to 350 million[1]. Patients with T2D are susceptible to infection and sepsis which may impact on T2D lethality and medical costs in health systems; the possible pleiotropic effect of OADs on sepsis outcomes has not yet been well validated in large-scale clinical studies. Previous studies[8,9,10] exploring the association between OADs and sepsis have produced conflicting results, which may be attributed to methodological issues such as small samples, limited follow-up periods, unconfirmed diagnosis of infection events, unknown OAD exposure periods relative to sepsis onset, or the confounding effects of differences in diabetes severity between groups. To investigate whether susceptibility to sepsis differed among patients with T2D taking different classes of OAD, we used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a nationwide nested case-control study that controlled for the effects of predisposing the host factors to sepsis
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