1005-OR: The SURPASS-CVOT Retinopathy Substudy: Retinal Status after Treatment with Tirzepatide or Dulaglutide in Patients with Type 2 Diabetes and Risk for Progressive Retinopathy

Introduction and Objective: While sustained glycemic control is effective to mitigate development or progression of diabetic retinopathy (DR), there are concerns that rapid reduction in chronic hyperglycemia may cause a worsening in DR after initiation of therapy. The SURPASS-CVOT retinopathy sub-study compared the effect of two incretin drugs with different glucose lowering potency, tirzepatide (TZP) and dulaglutide (dula), on retinal status in participants with long-standing type 2 diabetes, established atherosclerotic cardiovascular disease and either existing or high risk for DR. Methods: This pre-specified analysis evaluated retinal exams of SURPASS-CVOT DR sub-study participants randomized to TZP (n=449, up to 15 mg/week) or dula (n=471, 1.5 mg/week). Repeated, standardized fundoscopic photographs were obtained at baseline and after 12 months, and graded by blinded central readers on the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS) methodology, modified following the approach of the ACCORD Eye Study. Results: Baseline HbA1c was 8.69 (0.9%) and 8.69 (0.9%) (mean [SD]) for TZP and dula patients. At six months HbA1c was reduced more with TZP than on dula (-2.18%, -1.28%, p<0.001). Among patients without baseline DR, mean ETDRS scores at baseline and 12 months were 2.60 and 2.40 with TZP, and 2.68 and 2.38 for those receiving dula (mean changes -0.22 [p=0.27] vs. -0.24 [p=0.18], between-treatment p=0.96). In patients with baseline DR, scores were 6.47 and 6.48 (TZP) vs. 6.26 and 6.58 (dula) (mean changes 0.30 [p=0.04] vs. 0.40 [p=0.006], between-treatment p=0.63). Conclusion: Despite effective glucose-lowering with both drugs there were no meaningful mean changes in DR status in high-risk individuals with long-term uncontrolled diabetes, and changes in DR did not differ between the two treatments. The lack in progression of DR, despite substantial lowering of HbA1c, suggests favorable retinal safety associated with TZP use. Disclosure D.M. D'Alessio: Other - Clinical Trials; Current; Eli Lilly and Company. Consultant; Current; Sun Pharmaceutical Industries Ltd., Vertex Pharmaceuticals Incorporated. Z.Z. Nagy: None. I. Pavo: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. J. Kiljanski: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. V. Vijayanagaram: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. S.J. Nicholls: Other - SJN received grant/research support from AstraZeneca, NewAmsterdam Pharma, Amgen, Anthera, Cyclarity, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant for Abcentra, AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion; Current; Eli Lilly and Company. Funding Eli Lilly and Company