Tirzepatide may protect against diabetic retinopathy

medwireNews: Tirzepatide reduces the risk for, and progression of diabetic retinopathy compared with lifestyle intervention alone, suggest study findings published in Ophthalmology. 

“The growing popularity of medication assisted weight loss therapies have heightened concern that rapid blood sugar changes may trigger early development or worsening of [diabetic retinopathy],” say Szilard Kiss and colleagues, from Weill Cornell Medicine in New York, USA. 

To investigate, the researchers analyzed data on adults from the TriNetX US Collaborative Network who had type 1 or 2 diabetes, and diagnosis of overweight or obesity, or a BMI of at least 27 kg/m².

After propensity score matching for demographic, metabolic, and systemic covariates, a total of 173,846 patients were assessed, with 86,923 patients receiving the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1 receptor agonist tirzepatide and the same number receiving lifestyle interventions. The lifestyle interventions included dietary counseling, nutrition therapy, exercise counseling, or behavioral obesity counseling. Neither group had previously received weight-loss medications or undergone bariatric surgery. 

The participants had an average age of 57 years, around 52% were women, and 67% were White. The majority of patients had type 2 diabetes (83%) and a mean baseline glycated hemoglobin level of at least 6.5% (48 mmol/mol; 63–64%), and approximately 34% had a BMI of at least 40 kg/m². 

During 12 months of follow-up, 0.49% of people receiving tirzepatide developed mild non-proliferative diabetic retinopathy, compared with 0.57% of those receiving lifestyle interventions, giving a significant 14% risk reduction with tirzepatide. 

However, there was no significant difference between the two groups in the risk for moderate or severe non-proliferative diabetic retinopathy (0.19 vs 0.18%, and 0.07 vs 0.08%, respectively). 

Worsening of diabetic retinopathy also seemed to be reduced by tirzepatide, with a significant 30% risk reduction in proliferative diabetic retinopathy compared with lifestyle interventions (0.15 vs 0.22%), and a significant 38% risk reduction in diabetic retinopathy with macular edema (0.32 vs 0.51%).  

The researchers note that patients receiving tirzepatide treatment were significantly less likely than those receiving lifestyle interventions to experience complications associated with diabetic retinopathy, namely vitreous hemorrhage and tractional retinal detachment, with risk reductions of 39% and 63%, respectively. 

This in turn meant that the tirzepatide cohort had less need for intravitreal vascular endothelial growth factor inhibitor injections (0.09 vs 0.20%) and pan retinal photocoagulation (0.04 vs 0.07%), with corresponding risk reductions of 52% and 39%. 

Kiss and team conclude that “tirzepatide is unlikely to exacerbate diabetic retinopathy or related complications during the first year of therapy and may confer protection in this population.” 

They say that this protective effect may be due to tirzepatide’s dual action of mechanism, noting that “[e]xperimental data suggest that GIP-[receptor] signaling complements GLP-1-mediated pathways by further suppressing oxidative stress, inflammation, and vascular leakage in retinal tissues, potentially counteracting risks linked to abrupt glycemic change.” 

The team acknowledges that, as their study relied on diagnostic codes and had a relatively short observation duration, “[p]rospective studies that incorporate standardized retinal imaging and extend[ed] follow-up are needed to confirm the durability of this benefit and to refine recommendations for patients considering weight loss medications who are at risk for diabetic retinopathy.” 

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Ophthalmology 2026; doi:10.1016/j.ophtha.2026.01.013