Sodium-glucose cotransporter 2 inhibitors and risk of diabetic retinopathy: systematic review and meta-analysis

Abstract

Objective: This study aims to evaluate the relationship between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and diabetic retinopathy (DR) in diabetes mellitus.

Methods: We conducted a systematic search in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from their inception to November 9, 2024, for randomized controlled trials (RCTs) and real-world studies of SGLT2i in the treatment of diabetes mellitus. Outcome measures included DR incidence, DR progression, and sight-threatening diabetic retinopathy (STDR). The relative risk (RR) with its 95% confidence interval (CI) was used for the meta-analysis.

Results: A total of 16 RCTs and 19 real-world studies were included, involving 2,319,193 patients. The meta-analysis of RCTs indicated that, compared with the control group, SGLT2i was not significantly associated with DR incidence [RR = 0.92, 95% CI 0.60-1.44, I² = 0%]. The meta-analysis of real-world studies demonstrated that SGLT2i significantly reduced DR incidence [RR = 0.81, 95% CI 0.73-0.90, I² = 93%], DR progression [RR = 0.86, 95% CI 0.76-0.97, I² = 70%], and STDR [RR = 0.69, 95% CI 0.61-0.79, I² = 84%] compared with the control group. Subgroup analyses revealed that the type of control group might be a source of heterogeneity for DR incidence (p_interaction < 0.00001) and STDR (p_interaction = 0.01). Sensitivity analysis and assessment of publication bias indicated that the results were robust.

Conclusions: SGLT2i may have a role in reducing the risk of DR, but more multicenter, prospective, and high-quality RCTs are needed to validate our findings in the future.