Diabetic Retinopathy Risk in SGLT2i vs GLP1RA Initiators With CKD Stages 3-4 and Type 2 Diabetes
5 affiliations
- 1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- 2Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- 3Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- 4Atrius Health, Boston, MA
- 5New England Geriatric Research, Education and Clinical Center, VA Boston Healthcare System, Boston, MA
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.
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BibTeX
@article{hansrivijit2026diabetic,
title = {{Diabetic Retinopathy Risk in SGLT2i vs GLP1RA Initiators With CKD Stages 3-4 and Type 2 Diabetes}},
author = {Panupong Hansrivijit and Elisabetta Patorno and Helen Tesfaye and Deborah J. Wexler and Miin Roh and Julie M. Paik},
journal = {Kidney Medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xkme.2026.101518},
url = {https://doi.org/10.1016/j.xkme.2026.101518},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Diabetic Retinopathy Risk in SGLT2i vs GLP1RA Initiators With CKD Stages 3-4 and Type 2 Diabetes
AU - Panupong Hansrivijit
AU - Elisabetta Patorno
AU - Helen Tesfaye
AU - Deborah J. Wexler
AU - Miin Roh
AU - Julie M. Paik
PY - 2026
DA - 2026/09/09
JO - Kidney Medicine
DO - 10.1016/j.xkme.2026.101518
UR - https://doi.org/10.1016/j.xkme.2026.101518
AB - 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.
SN - 2590-0595
ER -