- Design
- Retrospective propensity-matched cohort (TriNetX)
- Population
- Adults with type 2 diabetes under eye care; 18,762–86,846 matched pairs per drug
- Primary outcome
- Incident DME and PDR within 3 years
- Effect
- Ibuprofen PDR HR 0.48 (0.41 to 0.56); cetirizine PDR HR 0.59 (0.46 to 0.77); prednisone PDR HR 0.36 (0.30 to 0.43)
A US TriNetX cohort matched adults with type 2 diabetes using cetirizine, ibuprofen or prednisone against non-users on 44 covariates, with fenofibrate as a positive control and gabapentin as a negative one. Matched pairs numbered 18,762 to 86,846.
Over three years, cetirizine was associated with less macular oedema (HR 0.62) and proliferative retinopathy (HR 0.59); ibuprofen with HR 0.63 and 0.48; prednisone with HR 0.46 and 0.36. Fenofibrate showed similar associations, and gabapentin none. Negative-control outcomes were near null for cetirizine and ibuprofen.
The design is careful for a database study, and the controls behaved as expected. But these are drugs taken intermittently for other reasons, and residual confounding cannot be excluded. It is a reason for a trial, not a prescription.
- Do not start anti-inflammatories to prevent diabetic retinopathy on this evidence.
- Continue to control glucose, blood pressure and lipids and to screen on schedule.
- Note that fenofibrate, with trial evidence, is the drug to discuss for retinopathy progression.
- Watch for prospective trials of low-cost anti-inflammatories.
Why it matters
It points to inflammation as a treatable driver of retinopathy, using drugs that cost almost nothing.
Don't overread it
Observational: it cannot show that these drugs prevent retinopathy.
The statistics, in plain English
Hazard ratios of 0.4 to 0.6 are large for common drugs, which is itself a warning sign for confounding. E-values of about 2.6 to 5 mean an unmeasured confounder would need a strong association with both drug use and retinopathy to explain the result away.
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