Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study

Aims/hypothesis: Early worsening of diabetic retinopathy (EWDR) has been described during treatment with glucagon-like peptide-1 receptor agonists including subcutaneous semaglutide. Whether EWDR occurs after initiating treatment with the potent glucagon-like peptide 1 / gastric inhibitory polypeptide receptor agonist tirzepatide is unknown. Methods: In this retrospective cohort study using real-world clinical data, we matched 3435 tirzepatide-exposed (≥180 days treatment) individuals with type 2 diabetes 1:1 with 3434 tirzepatide-unexposed individuals for sex, diabetes duration, retinopathy status, HbA1c, number of retinal screening episodes and use of glucose-lowering medications. New-onset diabetic retinopathy and retinopathy progression were explored using conditional logistic regression. Results: Individuals included in the study had tight baseline glycaemic control (mean HbA1c 56.1 ± 15.8 mmol/mol [7.28 ± 1.43%]). New-onset proliferative diabetic retinopathy (PDR) (grade R3M0, R3M1) occurred in 1.1% of tirzepatide-exposed (n=33) and 0.5% of tirzepatide-unexposed (n=17) individuals. Tirzepatide was significantly associated with new-onset PDR in multivariate analysis after adjustment for established risk factors (OR 2.15 [95% CI 1.24, 3.74], p<0.01). However, tirzepatide was also associated with reduced odds of new onset of retinopathy (OR 0.73 [95% CI 0.62, 0.86], p<0.001) in individuals without diabetic retinopathy (R0M0) at initiation in multivariate analysis, and was not significantly associated with retinopathy progression in individuals with mild non-proliferative diabetic retinopathy (NPDR, grade R1M0 or R1M1). Conclusions/interpretation: Tirzepatide therapy resulted in significantly increased odds of incident PDR, particularly in individuals with mild NPDR with maculopathy (grade R1M1), or moderate-to-severe NPDR with or without maculopathy (grade R2M0, R2M1). The increase in odds of progression would justify specialist ophthalmologist referral by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria.

Citation

Buckley, A. J., Tan, G. D., Gruszka-Goh, M., Scanlon, P. H., Ansari, I., & Suliman, S. G. I. (2025). Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study. Diabetologia, 10.1007/s00125-025-06466-8. Advance online publication. https://doi.org/10.1007/s00125-025-06466-8

DOI

10.1007/s00125-025-06466-8

URI

https://hdl.handle.net/20.500.14709/450

Usage rights

CC BY 4.0

License

https://creativecommons.org/licenses/by/4.0/