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Diabetic Retinopathy Risk in SGLT2i vs GLP1RA Initiators With CKD Stages 3-4 and Type 2 Diabetes

Year: 2026

Type: article

Abstract: Rationale & Objective Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) have demonstrated renal and cardiovascular benefits among patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). However, their comparative effects on diabetic retinopathy (DR) outcomes in patients with CKD stages 3-4 and T2D remain unclear. This study aimed to demonstrate the effect of SGLT2i vs GLP1RA in this population. Study Design Population-based, new-user, active comparator cohort study comparing SGLT2i versus GLP1RA initiators. Subjects were divided into 2 cohorts: (1) incident nonproliferative diabetic retinopathy (NPDR) and (2) DR progression cohort. Setting & Study Population Patients with CKD stages 3-4 and T2D across 3 US health care databases: Optum's de-identified Clinformatics Data Mart Database (2014-2024), Merative MarketScan (2014-2022), and Medicare Fee-for-Service (2014-2020). Selection Criteria for Studies Adults with a new prescription for either SGLT2i or GLP1RA without prior use in the preceding 365 days. The primary outcomes were incident NPDR and DR progression, identified through ICD-9/10 diagnosis codes and procedural codes for retinopathy treatments. Data Extraction Exposures, covariates, and outcomes were obtained from structured claims fields. Analytical Approach Both cohorts were analyzed using propensity score matching (1:1) to control for confounding. Incidence rates (IRs), rate differences, and hazard ratios (HRs) were calculated. Results After 1:1 propensity score matching, the study included 20,135 matched patient pairs in the incident NPDR cohort and 7,763 matched pairs in the DR progression cohort. For incident NPDR, there was no difference between SGLT2i and GLP1RA groups (IR 29.55 vs 30.38 per 1,000 person-years, respectively; HR 0.98 [95% CI, 0.87-1.10]). Similarly, DR progression was not different between groups (IR 32.73 vs 35.24 per 1,000 person-years; HR 0.92 [95% CI, 0.76-1.12]). Subgroup analyses showed no differences in HRs for both incident NPDR and DR progression across multiple predefined subgroups. Limitations Potential for residual confounding, outcome misclassification, and limited generalizability to non-U.S. populations. Conclusions Initiation of SGLT2i was not associated with a different risk of incident NPDR or DR progression compared with GLP1RA among patients with CKD stages 3-4 and T2D. Additional studies with extended follow-up are needed to better characterize long-term retinal safety profiles of these therapies. Plain-Language Summary People with chronic kidney disease and type 2 diabetes often need medicines that protect the kidneys and heart, but it is unclear whether one of the two used drug classes would impact eye disease caused by diabetes. We studied adults starting either sodium-glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in three US health databases. We separately examined new cases of early diabetic eye disease and worsening of existing eye disease. After matching patients with similar characteristics, we found that the 2 treatment groups had similar eye risks for both outcomes during the follow-up period. These findings matter because they suggest eye risk may not be the main reason to choose between these therapies, although longer-term studies are still needed.

Source: Kidney Medicine

DOI: 10.1016/j.xkme.2026.101518

Authors: Panupong Hansrivijit, Elisabetta Patorno, Helen Tesfaye, Deborah J. Wexler, Miin Roh, Julie M. Paik