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Updated: Aug 5, 2026

An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice
Published on: January 12, 2024
SGLT2 inhibitors and diabetic retinopathy progression: evidence from a retrospective cohort study and Mendelian
Mengya Wang1,2, Tianwei Liu3, Bojun Zhao1
1Department of Ophthalmology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.
Aims:
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).
Materials And Methods:
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.
Results:
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.
Conclusions:
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.
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