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. 2025 Sep;68(9):2069-2076.
doi: 10.1007/s00125-025-06466-8. Epub 2025 Jul 10.

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

Adam J Buckley  1 , Garry D Tan  2   3 , Marta Gruszka-Goh  4 , Peter H Scanlon  4 , Imran Ansari  5 , Sara G I Suliman  5
Affiliations

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

Adam J Buckley et al. Diabetologia. 2025 Sep.

Abstract

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.

Keywords: GIP; GLP-1RA; Retinopathy; Tirzepatide; Type 2 diabetes.

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Conflict of interest statement

Acknowledgements: The authors wish to acknowledge the contributions of A. Lari, A. Thampi, C. Suangco, J. Espinosa, J. Vasquez, M. Marquez, M. Jadoun, S. Cyriac and S. Alberto, retinal graders at ICLDC. GDT is supported by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Data availability: Data that underlie the results reported in this article after de‐identification (text, tables and figures) will be available. Data will be available for up to 5 years following publication for sharing with researchers who submit a study question which, in the opinion of the authors, can reasonably be addressed by the data. Enquiries should be directed to abuckley@icldc.ae. An institutional contract and data sharing agreement will be required. Funding: No external funding was received. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AJB performed data collection and statistical analysis and wrote the first draft of the manuscript. GDT, MG-G, PHS, IA and SGIS contributed to study methodology and revised and edited the final draft of the manuscript. The manuscript was approved for submission by all authors. AJB had access to the data used in this project and is the guarantor.

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