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NEW ORLEANS — Tirzepatide (Mounjaro) is not associated with increased risk for the development or progression of diabetic retinopathy in high-risk patients with type 2 diabetes (T2D), according to results from the SURPASS-CVOT retina substudy. 

“Tirzepatide produced greater glycemic improvement without worsening retinal status compared with dulaglutide over 36 months,” lead investigator David M. D’Alessio, MD, professor of medicine and chief of the division of endocrinology and metabolism at Duke University, Durham, North Carolina, said while presenting the data here at the American Diabetes Association (ADA) 2026 Scientific Sessions. 

Although diabetic retinopathy is driven by chronic hyperglycemia, and A1c reduction reduces its occurrence and severity, rapid correction of hyperglycemia has been linked to transient worsening diabetic retinopathy in several trials. 

Because tirzepatide can produce large, rapid A1c reduction, a substudy of Eli Lilly’s SURPASS-CVOT trial aimed to assess retinal status of participants with T2D and cardiovascular disease randomized to tirzepatide or dulaglutide as the active comparator. (A placebo was deemed unethical in such high-risk patients.) 

The groups didn’t differ in diabetic retinopathy progression, interventions, complications, or sustained visual acuity loss. Moreover, progression of retinal changes in both groups was gradual and consistent with the natural history of the disease, D’Alessio reported. 

“This provides some reassurance to clinicians taking care of people with diabetes. However, retinopathy is potentially catastrophic and most patients can be effectively treated by a skilled ophthalmologist. It is important to stay abreast with routine retinal screening,” he told Medscape Medical News. 

Greater Glucose Lowering

The SURPASS-CVOT retina substudy included 920 of the total 13,165 participants who had existing diabetic retinopathy or macular edema in either eye at baseline, or were considered high risk based on having a T2D duration of 15 years or longer and an A1c ≥ 8.0% at screening. Of these, 449 received tirzepatide (up to 15 mg/week) and 471 received dulaglutide (1.5 mg/week). Participants in the substudy underwent standardized fundoscopic photographs at baseline and 12, 18, 24, and 36 months. 

Baseline A1c was 8.69% in both treatment groups. At 6 months, A1c was reduced by more with tirzepatide than dulaglutide (2.18 vs 1.28 percentage points; P < .001).

The percentage of individuals with worsening in 2 or more steps of the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale at 36 months was 21.3% in the tirzepatide group versus 23.3% in the dulaglutide group, with an odds ratio of 0.89, a nonsignificant difference (P = .478). Time to first onset of a 2-step or greater progression also didn’t differ significantly between groups. 

There were also no differences between groups in secondary endpoints, including a composite of retinal photocoagulation, vitreous hemorrhage, anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection, vitrectomy, or significant visual loss (overall hazard ratio, 1.1 ). No significant between-treatment differences in ETDRS scale were seen in patients with or without diabetic retinopathy at baseline.

Rarely of Clinical Significance

Asked to comment, session moderator Lloyd Paul Aiello, MD, PhD, professor of ophthalmology and director of the Beetham Eye Institute at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News that the early worsening of retinopathy with rapid A1c reduction has been seen more often in people with type 1 diabetes than T2D, and that “very rarely is it of clinical significance. We only really worry about it at a very severe diabetic retinopathy stage. Usually it’s about the worst at 6 months, and by a year or 2, it’s back to normal. Improving glycemic control, even if you had early worsening, is always better than not improving the glycemic control.”

Aiello also noted that more information will be available from the ongoing FOCUS randomized trial by Novo Nordisk specifically investigating retinopathy risk with semaglutide. 

Meanwhile, he advised, “anytime you’re putting someone under tight [glycemic] control, look at it the same way as if you're putting someone on insulin, ensuring they're getting the appropriate eye care as it's suggested currently. If you do that, you're covered.”

D’Alessio is a consultant and/or advisor for Arrowhead Pharmaceuticals, Eli Lilly, Sun Pharmaceuticals, and Third Rock Ventures. Aiello is a consultant for Novo Nordisk, Ceramedix, Mantra Bio, and Optos. 

Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social