SGLT2 inhibitors and diabetic retinopathy progression: evidence from a retrospective cohort study and Mendelian randomization analysis.

Authors

Mengya Wang, Tianwei Liu, Bojun Zhao

Published in

Frontiers in endocrinology. Volume 17. Pages 1846454. Epub Jul 16, 2026.

Abstract

To investigate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) use and diabetic retinopathy (DR) progression, and to explore supporting genetic and molecular evidence using a retrospective cohort study with Mendelian randomization (MR).
In this retrospective cohort study at Shandong Provincial Hospital from January 2023 to December 2024, patients with type 2 diabetes on stable SGLT2i plus basal insulin (SGLT2i+INS) or sulfonylureas plus basal insulin (SUL+INS) were included. Wide-field swept-source optical coherence tomography angiography (SS-OCTA) was used to assess retinal microvascular parameters. Kaplan-Meier and Cox regression analyses evaluated DR progression and new-onset diabetic macular edema with sensitivity analyses performed to assess robustness. An exploratory nomogram was developed and evaluated by decision curve analysis. Two-sample MR and two-step mediation analyses were conducted to examine the genetic association between SGLT2 and DR and to identify potential mediating metabolites and plasma proteins.
A total of 191 eyes were included: 56 in the SGLT2i+INS group and 135 in the SUL+INS group. SGLT2i+INS was associated with a lower risk of DR progression (HR = 0.40, 95% CI 0.19-0.84; P = 0.016) and reduced cumulative incidence (log-rank P = 0.032). The exploratory OCTA-based nomogram showed modest performance (C-index=0.705). MR supported an association between genetically proxied SGLT2 and DR risk (OR = 1.21, 95% CI 1.05-1.39; P = 0.009). Nine metabolites and five plasma proteins showed nominal evidence of potential mediation.
Among insulin-treated patients with type 2 diabetes, SGLT2i use was associated with a lower risk of DR progression than sulfonylurea use. OCTA parameters and candidate molecular mediators may provide exploratory prognostic and biological insights, warranting validation in larger prospective studies and randomized trials.

PMID:
42534740
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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