While these findings are encouraging, further prospective studies are needed to confirm this potential benefit and to guide recommendations for patients considering weight-loss therapies who are at risk for diabetic retinopathy.
Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist approved for weight management, provides robust metabolic and glycaemic benefits. Nevertheless, its long-term impact on diabetic retinopathy has remained uncertain, particularly in light of earlier concerns surrounding incretin-based therapies. To clarify this issue, researchers conducted a large, multicenter, population-based cohort study to examine the relationship between tirzepatide use and outcomes of diabetic retinopathy.
The study, published in Ophthalmology, was led by Jaffer Shah from the Department of Ophthalmology, Weill Cornell Medicine, New York. Using data from the TriNetX US Collaborative Network, investigators identified patients with diabetes and overweight or obesity who initiated tirzepatide and compared them with a matched cohort receiving lifestyle intervention alone, without exposure to weight-loss medications.
A propensity score–matched design was used to balance demographic, metabolic, and systemic factors between the two groups. After matching, the analysis included 173,846 patients, with 86,923 individuals in each cohort. The mean age of participants was 56.9 years, and 52% were women. Outcomes were assessed over a 12-month follow-up period.
The primary endpoints included new-onset diabetic retinopathy, progression to more advanced stages, and the need for ocular interventions such as intravitreal anti–vascular endothelial growth factor injections and pan-retinal photocoagulation.
The researchers reported the following findings:
- Compared with lifestyle intervention alone, tirzepatide use was associated with significantly lower risks across a wide range of diabetic retinopathy–related outcomes.
- Tirzepatide users showed a reduced incidence of mild nonproliferative diabetic retinopathy.
- The risk of progression to proliferative diabetic retinopathy was lower among patients receiving tirzepatide.
- The likelihood of developing diabetic retinopathy with macular edema was markedly reduced in the tirzepatide group.
- Serious vision-threatening complications, including vitreous hemorrhage, occurred less frequently with tirzepatide use.
- The incidence of tractional retinal detachment was lower among patients treated with tirzepatide.
- Tirzepatide use was associated with fewer complications requiring ocular treatment.
- Rates of intravitreal anti-VEGF injections were significantly lower in patients receiving tirzepatide.
- The need for pan-retinal photocoagulation was reduced in the tirzepatide group compared with matched controls.
The authors cautioned that the observational nature of the study limits causal conclusions and that unmeasured confounding cannot be fully excluded. They emphasized the need for prospective, randomized trials to confirm these findings and to better inform clinical decision-making. However, the results suggest that tirzepatide may offer a favorable retinal safety profile and potential protective benefits for patients with diabetes at risk of diabetic retinopathy.
Reference:
Shah J, Razavi P, Festok M, Ahmed H, Mahrous MA, Kovacs KD, Kiss S. Tirzepatide and Reduced Risk of Diabetic Retinopathy and Related Complications: A Multicenter U.S. Cohort Study. Ophthalmology. 2026 Jan 21:S0161-6420(26)00019-9. doi: 10.1016/j.ophtha.2026.01.013. Epub ahead of print. PMID: 41577258.
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