Thiazolidinedione Use and Risk of Bacterial Enteric Infection Among Adults With Type 2 Diabetes Mellitus

Thiazolidinediones are peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists commonly used to treat type 2 diabetes mellitus. In experimental models, epithelial PPAR-γ signaling contributes to colonization resistance against bacterial enteric pathogens by shaping oxygen and nitrate luminal bioavailability. Whether the use of PPAR-γ agonists in humans is associated with reduced risk of bacterial enteric infection is unknown.

To investigate whether users of thiazolidinediones (PPAR-γ agonists) have decreased risk of bacterial enteric infection, we performed a retrospective nationwide analysis using the cloud-based TriNetX Analytics Platform which aggregates health records from 117 million patients across 66 US healthcare organizations. We compared the risk of bacterial enteric infection among patients with diabetes prescribed thiazolidinediones, a class of PPAR-γ agonists, compared with users of other glucose-lowering medications.

Among 85 916 thiazolidinedione users categorized as being at low risk for bacterial enteric infection (no prior history of infection) and 1974 persons identified as being at high risk (prior history of bacterial enteric infection), the risk of bacterial enteric infection was reduced by 49% (RR 0.51, 95% confidence interval [CI] .32-.82) and 22% (RR 0.78, 95% CI .69-.88) respectively, compared to users of other glucose-lowering medications. This reduction in risk was consistent among high-risk individuals, regardless of sex or age. Similar results were observed in high-risk patients when thiazolidinedione users were directly compared to those on DPP-4 inhibitors.

These findings demonstrate an association between PPAR-γ agonist use and a reduced risk of bacterial enteric infection and support further clinical investigation.