This retrospective propensity score-matched cohort study examined whether adults with type 2 diabetes (T2DM) using cetirizine, ibuprofen, or prednisone had a lower 3-year incidence of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), using the TriNetX US Collaborative Network (2005–2025). Fenofibrate served as a positive control and gabapentin as a negative control.
All three anti-inflammatory drugs were associated with significantly reduced DME and PDR risk vs. non-users: cetirizine (DME HR 0.62, PDR HR 0.59), ibuprofen (DME HR 0.63, PDR HR 0.48), and prednisone (DME HR 0.46, PDR HR 0.36). Effect sizes were comparable to the fenofibrate positive control; gabapentin (negative control) showed no association (DME HR 0.95, PDR HR 1.04).
- Retrospective design cannot establish causality; residual confounding remains possible despite propensity matching on 44 covariates. - Prednisone and fenofibrate showed mild protective bias on the negative-control outcome panel, suggesting some unmeasured confounding. - Drug exposure was defined by two documented uses only; dose, duration, and adherence data are limited.
These findings are hypothesis-generating, not practice-changing — prospective trials are needed before recommending cetirizine, ibuprofen, or prednisone specifically to prevent DME or PDR. Clinicians should note that commonly used anti-inflammatory agents may warrant further study as adjuncts in diabetic eye disease prevention.
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