Thiazolidinedione use and risk of bacterial enteric infection among adults with type 2 diabetes mellitus

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ID: 322339
2026
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Abstract
Abstract Background 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 use of PPAR-γ agonists in humans is associate[ABS]d with reduced risk of bacterial enteric infection is unknown. Methods To investigate whether users of thiazolidinediones (PPAR-γ agonists) have decreased risk of bacterial enteric infection, we performed a retrospective nationwide analysis with the cloud-based TriNetX Analytics Platform which aggregates health records from 117 million patients across 66 US healthcare organizations, to assess the risk of bacterial enteric infection among diabetic patients prescribed thiazolidinediones, a class of PPAR-γ agonists, compared with other anti-diabetes medications. Results Among 85,916 thiazolidinedione users categorized as low-risk for bacterial enteric infection (no prior history of infection) and 1,974 persons identified as high-risk (prior history of bacterial enteric infection), the likelihood of bacterial enteric infection was reduced by 49% (RR 0.51, 95% CI 0.32-0.82) and 22% (RR 0.78, 95% CI 0.69-0.88) respectively, compared to users of other anti-diabetes medications. This reduction in risk was consistent across high-risk individuals, regardless of sex or age. Similar results were replicated in high-risk patients when thiazolidinedione users were directly compared to those on DPP-4 inhibitors. Conclusion These findings demonstrate an association between PPAR-γ agonist use and reduced risk of bacterial enteric infection and support further clinical investigation.
Reference Key
openalex_W7170142751 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Morgan Birabaharan, David C. Kaelber, Victor Nizet, Amir Zarrinpar
Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag457
URL
https://doi.org/10.1093/ofid/ofag457
Keywords Keywords not found

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